本申請包括計(jì)算機(jī)可讀形式的序列表，將其通過引用結(jié)合在此。發(fā)明背景發(fā)明領(lǐng)域本發(fā)明涉及α-淀粉酶變體(具有α-淀粉酶活性的多肽)、編碼α-淀粉酶的核酸、生產(chǎn)α-淀粉酶的方法、包括α-淀粉酶的組合物以及使用α-淀粉酶的方法。相關(guān)領(lǐng)域描述α-淀粉酶(α-1,4-葡聚糖-4-葡聚糖水解酶，E.C.3.2.1.1)構(gòu)成一組酶，這些酶催化淀粉以及其他直鏈和支鏈1,4-糖苷寡糖和多糖的水解。α-淀粉酶在工業(yè)上用于若干種已知應(yīng)用的用途具有悠久歷史，這些用途如洗滌劑、烘焙、釀造、淀粉液化和糖化，例如在制備高果糖糖漿中或用作從淀粉生產(chǎn)乙醇的一部分。α-淀粉酶的這些應(yīng)用和其他應(yīng)用是已知的并且利用源自微生物的α-淀粉酶，特別是細(xì)菌α-淀粉酶。屬于首先被使用的細(xì)菌α-淀粉酶是來自地衣芽孢桿菌(B.licheniformis)的α-淀粉酶，還稱作特妙淀粉酶(Termamyl)，所述特妙淀粉酶已經(jīng)被充分表征并且這種酶的晶體結(jié)構(gòu)已經(jīng)被確定。芽孢桿菌淀粉酶如特妙淀粉酶、AA560(WO2000/060060)和SP707(通過冢本(Tsukamoto)等人，1988，生物化學(xué)和生物物理研究通訊(Biochem.Biophys.Res.Comm.)151:25-31)形成一個特定的已經(jīng)用于洗滌劑中的α-淀粉酶的組。這些淀粉酶已經(jīng)經(jīng)修飾以改進(jìn)洗滌劑中的穩(wěn)定性。WO96/23873例如披露了缺失SP707(WO96/23873的SEQIDNO:7)的氨基酸181+182或氨基酸183+184以改進(jìn)此淀粉酶的穩(wěn)定性。WO96/23873另外披露了通過用例如亮氨酸取代M202來修飾SP707淀粉酶以使該分子對氧化保持穩(wěn)定。因而，修飾淀粉酶來改進(jìn)某些特性是已知的。最近，出于環(huán)境原因，在洗滌、餐具洗滌和/或清潔過程中降低溫度已經(jīng)變得日益重要。盡管當(dāng)前洗滌劑酶組合物的功效，但尤其由于低(例如冷水)洗滌溫度和更短洗滌循環(huán)，有許多難以完全去除的污漬。因而，對可以在低溫下起作用并同時保留或增加令人希望的α-淀粉酶特性如比活性(淀粉分解活性)、穩(wěn)定性、污漬去除效果和/或洗滌性能的淀粉分解酶存在需要。本發(fā)明的諸位發(fā)明人先前已經(jīng)發(fā)現(xiàn)，SEQIDNO:2的淀粉酶變體在洗滌劑中具有非常好的穩(wěn)定性(在歐洲專利申請?zhí)?3194116.3中披露為具有(H183+G184)缺失和(N195F+I206Y)取代的SEQIDNO:1)。本發(fā)明的目的是提高該變體的洗滌性能。因而，本發(fā)明的目的是提供具有α-淀粉酶活性(α-淀粉酶)的多肽，這些多肽在衣物洗滌和/或餐具洗滌中具有高性能、尤其在低溫具有高洗滌性能。本發(fā)明的又一目的是提供在洗滌劑組合物中、特別地在液體衣物和/或餐具洗滌洗滌劑組合物中具有高穩(wěn)定性的α-淀粉酶。又一目的是提供在粉末狀洗滌劑組合物中具有高穩(wěn)定性的α-淀粉酶和/或在洗滌劑中存儲后具有高淀粉酶活性的α-淀粉酶。特別地，本發(fā)明的目的是提供在洗滌劑組合物中具有高穩(wěn)定性并且在低溫(如15℃)具有高洗滌性能兩者的α-淀粉酶，其改進(jìn)的洗滌性能是根據(jù)“使用自動機(jī)械應(yīng)力測定的α-淀粉酶的洗滌性能”部分中使用標(biāo)準(zhǔn)洗滌劑A或J確定的。具體而言，本發(fā)明的目的是提供以下α-淀粉酶，這些α-淀粉酶與SEQIDNO:2的親本α-淀粉酶相比，或可替代地與其他密切相關(guān)的α-淀粉酶如例如SP707α-淀粉酶(SEQIDNO:4)相比，在15℃下具有改進(jìn)的洗滌性能。發(fā)明既述本發(fā)明涉及α-淀粉酶變體，該變體包括a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或三個或四個位置處的缺失和/或取代，以及b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，并且該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性。本發(fā)明進(jìn)一步涉及編碼這些變體的分離的多核苷酸；包含這些多核苷酸的核酸構(gòu)建體、載體以及宿主細(xì)胞；包含這些變體的組合物；以及生產(chǎn)這些變體的方法。本發(fā)明進(jìn)一步涉及包含所述變體的組合物如洗滌劑組合物，并且涉及這些變體的用途。定義A-、B-和C-結(jié)構(gòu)域：α-淀粉酶的結(jié)構(gòu)包括三個不同結(jié)構(gòu)域A、B和C，參見例如馬姬絲(Machius)等人，1995，分子生物學(xué)雜志(J.Mol.Biol.)246:545-559。術(shù)語“結(jié)構(gòu)域”意指本身形成完整分子的不同且獨(dú)立的子結(jié)構(gòu)的多肽區(qū)域。α-淀粉酶由攜帶活性位點(diǎn)殘基的β/α-8桶狀結(jié)構(gòu)(其記為A-結(jié)構(gòu)域)、β-片層3和α-螺旋3之間相當(dāng)長的環(huán)狀結(jié)構(gòu)(其記為B-結(jié)構(gòu)域)(一起；“A和B結(jié)構(gòu)域”)和C-結(jié)構(gòu)域組成，并且在某些情況下還包含糖結(jié)合結(jié)構(gòu)域(例如，W02005/001064；馬奇斯(Machius)等人，見上文)。α-淀粉酶的結(jié)構(gòu)域可以通過結(jié)構(gòu)分析來確定，如使用結(jié)晶學(xué)技術(shù)。用于確定α-淀粉酶的結(jié)構(gòu)域的可替代方法是通過該α-淀粉酶與另一個已經(jīng)確定結(jié)構(gòu)域的α-淀粉酶的氨基酸序列的序列比對。與例如已經(jīng)確定了C-結(jié)構(gòu)域的α-淀粉酶中的C-結(jié)構(gòu)域序列對齊的序列可以視為給定α-淀粉酶的C-結(jié)構(gòu)域。A和B結(jié)構(gòu)域：如在此所使用的術(shù)語“A和B結(jié)構(gòu)域”意指這些視為一個單元的兩個結(jié)構(gòu)域，然而該C結(jié)構(gòu)域是這些α-淀粉酶的另一個單元。因而，“A和B結(jié)構(gòu)域”的氨基酸序列被理解為包括“A和B結(jié)構(gòu)域”和其他結(jié)構(gòu)域(如C結(jié)構(gòu)域)的α-淀粉酶的序列的一個序列或序列的一部分。如在此所使用，α-淀粉酶的“A和B結(jié)構(gòu)域”對應(yīng)于SEQIDNO:4的氨基酸1-399。α-淀粉酶：術(shù)語“α-淀粉酶”與術(shù)語“具有α-淀粉酶活性的多肽”是同義的?！唉?淀粉酶活性”意指α-1,4-葡聚糖-4-葡聚糖水解酶(E.C.3.2.1.1)的活性，其構(gòu)成一組催化淀粉以及其他直鏈和支鏈1,4-糖苷寡糖-和多糖的水解的酶。出于本發(fā)明的目的，根據(jù)方法中所述的程序確定α-淀粉酶活性。在一方面，本發(fā)明的α-淀粉酶具有SEQIDNO:2的成熟多肽的至少20％，例如至少40％、至少50％、至少60％、至少70％、至少80％、至少90％、至少95％或至少100％的α-淀粉酶活性。等位基因變體：術(shù)語“等位基因變體”意指占用同一染色體位點(diǎn)的一種基因的兩個或更多個替代形式中的任一者。等位基因變異由突變天然產(chǎn)生，并且可以導(dǎo)致群體內(nèi)多態(tài)性?；蛲蛔兛梢允浅聊?在所編碼的多肽中沒有改變)或可編碼具有改變的氨基酸序列的多肽。多肽的等位基因變體是由基因的等位基因變體編碼的多肽。催化結(jié)構(gòu)域：術(shù)語“催化結(jié)構(gòu)域”意思指酶的包含該酶的催化機(jī)器的區(qū)域。C結(jié)構(gòu)域：如在此所使用，α-淀粉酶的“C結(jié)構(gòu)域”對應(yīng)于SEQIDNO:4的400-485。因而，α-淀粉酶的C結(jié)構(gòu)域可以通過所述α-淀粉酶與SEQIDNO:4的α-淀粉酶的比對來發(fā)現(xiàn)。所述與SEQIDNO:4的氨基酸400-485比對的α-淀粉酶的部分是根據(jù)本發(fā)明α-淀粉酶的“C結(jié)構(gòu)域”。對應(yīng)于：如在此所使用的術(shù)語“對應(yīng)于”是指確定序列的特定氨基酸的方法，其中參考特定氨基酸序列。例如出于本發(fā)明的目的，當(dāng)參考特定氨基酸位置時，本領(lǐng)域技術(shù)人員能夠?qū)⒘硪粋€氨基酸序列與已經(jīng)參考的所述氨基酸序列進(jìn)行比對，以便在所述另一氨基酸序列中確定哪個特定氨基酸可能是感興趣的。已經(jīng)在本文其他地方描述了另一氨基酸序列與例如SEQIDNO:1中所示的序列或本文列出的任何其他序列的比對?？墒褂每商娲谋葘Ψ椒?，并且對于技術(shù)人員是熟知的。洗滌劑組合物：如在此所使用的術(shù)語“洗滌劑組合物”是指適合用于在洗滌劑領(lǐng)域內(nèi)使用的組合物，如用于在洗衣和餐具洗滌中使用。洗滌劑組合物可以處于液體或粉末形式，并且可適用于手洗或自動洗滌兩者。因此除非上下文另有說明，術(shù)語“洗滌劑組合物”包括顆粒狀或粉狀的全效或重垢清洗劑，尤其是所謂的重垢液(HDL)類型；液體細(xì)薄織物洗滌劑；手洗餐具清洗劑或輕垢餐具清洗劑，尤其是高泡沫型的那些；機(jī)洗餐具洗滌劑，包括用于居家及機(jī)構(gòu)使用的多種片型、顆粒型、液體型以及沖洗助劑型；液體清潔和消毒劑，包括抗菌洗手液類型、清潔棒、皂棒、漱口液、義齒清潔劑、汽車或地毯清潔劑、浴室清潔劑；洗發(fā)香波和護(hù)發(fā)素；沐浴凝膠、沐浴露；金屬清洗劑；以及清潔助劑，如漂白劑添加劑和“去污棒”或預(yù)處理類型。就預(yù)期用于弄臟的物體清潔的洗滌介質(zhì)中的混合物而言，使用術(shù)語“洗滌劑組合物”和“洗滌劑配制品”。在一些實(shí)施例中，就洗滌織物和/或衣服而言，使用該術(shù)語(例如，“衣物洗滌劑”)。在替代性實(shí)施例中，該術(shù)語是指例如用于清潔餐具、刀具等的那些的其他洗滌劑(例如“餐具清洗洗滌劑”)。它并不意圖使本發(fā)明限于任何特定的洗滌劑配制品或組合物。術(shù)語“洗滌劑組合物”不旨在限于包含表面活性劑的組合物。其意圖是，除了本文所述的變體以外，這些洗滌劑組合物可以包括：例如表面活性劑、助洗劑、螯合劑(chelator)或螯合試劑(chelatingagent)、漂白系統(tǒng)或漂白組分、聚合物、織物調(diào)理劑、增泡劑、抑泡劑、染料、香料、晦暗抑制劑、光學(xué)增亮劑、殺細(xì)菌劑、殺真菌劑、污垢懸浮劑、防腐蝕劑、酶抑制劑或穩(wěn)定劑、酶激活劑、一種或多種轉(zhuǎn)移酶、水解酶、氧化還原酶、上藍(lán)劑和熒光染料、抗氧化劑、和/或增溶劑。表達(dá)：術(shù)語“表達(dá)”包括涉及變體產(chǎn)生的任何步驟，包括但不限于，轉(zhuǎn)錄、轉(zhuǎn)錄后修飾、翻譯、翻譯后修飾以及分泌。表達(dá)載體：術(shù)語“表達(dá)載體”意指線性或環(huán)狀DNA分子，該分子包括編碼變體的多核苷酸并且該多核苷酸可操作地與提供用于其表達(dá)的控制序列相連接。片段：術(shù)語“片段”意指從成熟多肽的氨基和/或羧基末端缺失一個或多個(例如，數(shù)個)氨基酸的多肽；其中該片段具有α-淀粉酶活性。高嚴(yán)格條件：術(shù)語“高嚴(yán)格條件”意指對于長度為至少100個核苷酸的探針而言，遵循標(biāo)準(zhǔn)DNA印跡程序，在42℃下在5XSSPE、0.3％SDS、200微克/ml剪切并變性的鮭魚精子DNA和50％甲酰胺中預(yù)雜交和雜交12至24小時。最后在65℃下使用2XSSC、0.2％SDS將載體材料洗滌三次，每次15分鐘。宿主細(xì)胞：術(shù)語“宿主細(xì)胞”意指易于用包含本發(fā)明的多核苷酸的核酸構(gòu)建體或表達(dá)載體轉(zhuǎn)化、轉(zhuǎn)染、轉(zhuǎn)導(dǎo)等的任何細(xì)胞類型。術(shù)語“宿主細(xì)胞”涵蓋由于復(fù)制期間發(fā)生的突變而與親本細(xì)胞不同的親本細(xì)胞的任何后代。免疫交叉反應(yīng)性：如本文所使用的術(shù)語“與抗體具有免疫交叉反應(yīng)性的多肽”是指由針對SEQIDNO:1或2的多肽產(chǎn)生的抗體結(jié)合的任何多肽。當(dāng)不必具有如SEQIDNO:1或2所示的序列的多肽被抗體結(jié)合，并從而提供交叉反應(yīng)性時，其表明該多肽可以與SEQIDNO:1或2的多肽具有相似的特征。交叉反應(yīng)性的測定可以通過ELISA進(jìn)行，ELISA包括以下步驟：(i)將感興趣的多肽粘附到ELISA板上；(ii)加入針對SEQIDNO:1或2的多肽產(chǎn)生的抗體；(iii)加入結(jié)合針對SEQIDNO:1或2的多肽產(chǎn)生的抗體的第二標(biāo)記抗體；和(iv)測量來自結(jié)合的第二抗體的信號?？梢允褂脺y定免疫交叉反應(yīng)性的其他方法，并且是在技術(shù)人員的知識范圍內(nèi)。改進(jìn)的特性：術(shù)語“改進(jìn)的特性”意指一種與本發(fā)明的多肽相關(guān)的特征，該特征相比于SEQIDNO:2的成熟多肽得到了改進(jìn)。此類改進(jìn)的特性包括但不限于催化效率、催化速率、化學(xué)穩(wěn)定性、螯合劑穩(wěn)定性、氧化穩(wěn)定性、pH活性、pH穩(wěn)定性、比活性、洗滌劑穩(wěn)定性、底物結(jié)合、底物切割、底物特異性、底物穩(wěn)定性、表面特性、熱活性、以及熱穩(wěn)定性、和改進(jìn)的洗滌性能，特別是在低溫下，如5℃和40℃之間的溫度下(如在15℃下)的改進(jìn)的洗滌性能。可以改進(jìn)的另一種特性是該分子在洗滌劑組合物中、特別是在液體洗滌劑組合物中存儲期間的穩(wěn)定性。穩(wěn)定性或洗滌性能的改進(jìn)是相對于SEQIDNO:2的淀粉酶的穩(wěn)定性或相對于具有與該變體相同的a)的改變的SEQIDNO:1的多肽的穩(wěn)定性。洗滌性能：在本發(fā)明背景下，使用術(shù)語“洗滌性能”作為酶在例如衣物或硬表面清潔如餐具洗滌期間去除存在于待清潔的物體上的淀粉或含淀粉污漬的能力。術(shù)語“洗滌性能”包括通常清潔例如硬表面清潔，如在餐具洗滌中，但還包括在紡織品如衣物上的洗滌性能，并且還包括工業(yè)清潔和機(jī)構(gòu)清潔。該洗滌性能可以通過計(jì)算所謂的強(qiáng)度值來量化。改進(jìn)的洗滌性能：術(shù)語“改進(jìn)的洗滌性能”在此定義為相對于SEQIDNO:2的淀粉酶的洗滌性能，或相對于具有與該變體相同的a)的改變的SEQIDNO:1的多肽而展現(xiàn)出本發(fā)明的淀粉酶的洗滌性能的改變。該改變可以例如被視為增加的污漬去除。根據(jù)實(shí)例1確定改進(jìn)的洗滌性能。如果在實(shí)施例1中列出的一種或多種條件下改進(jìn)因子(IF)高于1.0，優(yōu)選地高于1.05，則洗滌性能得到了改進(jìn)。即，在標(biāo)準(zhǔn)洗滌劑A中在15℃下，其中該α-淀粉酶變體濃度是0.2mg/L；或在標(biāo)準(zhǔn)洗滌劑A中在40℃下，其中該α-淀粉酶變體濃度是0.05mg/L；或在標(biāo)準(zhǔn)洗滌劑J中在15℃下，其中該α-淀粉酶變體濃度是0.2mg/L；或在標(biāo)準(zhǔn)洗滌劑J中在30℃下，其中該α-淀粉酶變體濃度是0.05mg/L。實(shí)例1中描述了這些洗滌條件。術(shù)語“洗滌性能”包括通常清潔例如硬表面清潔，如在餐具洗滌中，但還包括在紡織品如衣物上的洗滌性能，并且還包括工業(yè)清潔和機(jī)構(gòu)清潔。可以通過比較如在本文的定義中描述的δ強(qiáng)度來測量改進(jìn)的洗滌性能。δ強(qiáng)度：在此將術(shù)語“δ強(qiáng)度”或“δ強(qiáng)度值”定義為測試材料的強(qiáng)度測量結(jié)果，該測試材料是例如小塊布樣CS-28(測試材料BV中心(CenterforTestmaterialsBV)，郵政信箱120，3133KT弗拉爾丁恩(Vlaardingen)，荷蘭)或硬表面。將該小塊布樣與作為背景的在相同條件下洗滌的該小塊布樣的一部分一起測量。δ強(qiáng)度是用淀粉酶洗滌的測試材料的強(qiáng)度值減去未用淀粉酶洗滌的測試材料的強(qiáng)度值。紡織品：紡織品樣品CS-28(棉花上的大米淀粉)獲得自測試材料BV中心(CenterForTestmaterialsBV)，郵政信箱120，3133KT弗拉爾丁恩，荷蘭。低溫：“低溫”是5℃-40℃，例如5℃-35℃，優(yōu)選5℃-30℃，更優(yōu)選5℃-25℃，更優(yōu)選5℃-20℃，最優(yōu)選5℃-15℃，并且特別是5℃-10℃的溫度。在一個優(yōu)選實(shí)施例中，“低溫”是10℃-35℃，優(yōu)選10℃-30℃，更優(yōu)選10℃-25℃，最優(yōu)選10℃-20℃，并且特別是10℃-15℃的溫度。最優(yōu)選的，低溫意指15℃。強(qiáng)度值：洗滌性能可以被測量為亮度，表達(dá)為當(dāng)用白光照亮?xí)r從樣品反射的光的強(qiáng)度。當(dāng)樣品受到污染時，反射光的強(qiáng)度低于干凈樣品的反射光的強(qiáng)度。因此，反射光的強(qiáng)度可以用于測量洗滌性能，其中更高的強(qiáng)度值與更高的洗滌性能相關(guān)。使用專業(yè)平板掃描儀(EPSONExpression10000XL,EPSON)進(jìn)行顏色測量，該掃描儀用于捕獲所洗滌紡織品的圖像。為了從掃描圖像中提取光強(qiáng)度的值，將來自圖像的48→24位彩色像素值轉(zhuǎn)化為紅色、綠色和藍(lán)色(rgb)的值。通過將rgb值作為向量相加在一起并然后考慮所得向量的長度可以計(jì)算強(qiáng)度值(Int)：改進(jìn)因子：改進(jìn)因子(IF)是酶樣品的δ強(qiáng)度與主鏈或參考，即SEQIDNO:2的δ強(qiáng)度的比率。分離的：術(shù)語“分離的”意指處于自然界中不存在的形式或環(huán)境中的物質(zhì)。分離的物質(zhì)的非限制性實(shí)例包括(1)任何非天然存在的物質(zhì)；(2)至少部分地從與其在自然界中相關(guān)聯(lián)的一種或多種或全部天然存在的組分中除去的任何物質(zhì)，包括但不局限于任何酶、變體、核酸、蛋白質(zhì)、肽或輔因子；(3)相對于自然界中發(fā)現(xiàn)的那種物質(zhì)通過人工手動修飾的任何物質(zhì)；或者(4)通過相對于與其天然相關(guān)聯(lián)的其他組分增加該物質(zhì)的量而修飾的任何物質(zhì)(例如，編碼該物質(zhì)的基因的多個拷貝；比與編碼該物質(zhì)的基因天然相關(guān)聯(lián)的啟動子更強(qiáng)的啟動子的使用)。分離的物質(zhì)可以存在于發(fā)酵液樣品中。成熟多肽：術(shù)語“成熟多肽”意指在翻譯和任何翻譯后修飾如N-末端加工、C-末端截短、糖基化作用、磷酸化作用等之后處于其最終形式的多肽。在一個方面，成熟多肽是SEQIDNO:1的氨基酸1至485。在另一個方面，成熟多肽是SEQIDNO:2的氨基酸1至483。本領(lǐng)域已知，宿主細(xì)胞可以產(chǎn)生由同一多核苷酸表達(dá)的兩種或更多種不同成熟多肽(即，具有不同C-末端和/或N-末端氨基酸)的混合物。本領(lǐng)域還已知，不同的宿主細(xì)胞不同地加工多肽，并且因此一個表達(dá)一種多核苷酸的宿主細(xì)胞當(dāng)與另一個表達(dá)相同多核苷酸的宿主細(xì)胞相比時可以產(chǎn)生一種不同的成熟多肽(例如，具有一個不同的C-末端和/或N-末端氨基酸)。成熟多肽編碼序列：術(shù)語“成熟多肽編碼序列”意指編碼具有α-淀粉酶活性的成熟多肽的多核苷酸。中嚴(yán)格條件：術(shù)語“中嚴(yán)格條件”意指對于長度為至少100個核苷酸的探針而言，遵循標(biāo)準(zhǔn)DNA印跡程序，在42℃下在5XSSPE、0.3％SDS、200微克/ml剪切并變性的鮭魚精子DNA和35％甲酰胺中預(yù)雜交和雜交12至24小時。最后在55℃下使用2XSSC、0.2％SDS將載體材料洗滌三次，每次15分鐘。中-高嚴(yán)格條件：術(shù)語“中-高嚴(yán)格條件”意指對于長度為至少100個核苷酸的探針而言，遵循標(biāo)準(zhǔn)DNA印跡程序，在42℃下在5XSSPE、0.3％SDS、200微克/ml剪切并變性的鮭魚精子DNA以及35％甲酰胺中預(yù)雜交和雜交12至24小時。最后在60℃下使用2XSSC、0.2％SDS將載體材料洗滌三次，每次15分鐘。突變體：術(shù)語“突變體”意指編碼變體的多核苷酸。核酸構(gòu)建體：術(shù)語“核酸構(gòu)建體”意指單-鏈或雙鏈的核酸分子，該核酸分子是從天然存在的基因中分離的，或以本來不存在于自然界中的方式被修飾成含有核酸的區(qū)段，或是合成的，該核酸分子包括一個或多個控制序列。可操作地連接：術(shù)語“可操作地連接”意指如下的構(gòu)造，其中，控制序列相對于多核苷酸的編碼序列安置在適當(dāng)位置，從而使得該控制序列指導(dǎo)該編碼序列的表達(dá)。親本或親本α-淀粉酶：術(shù)語“親本”或“親本α-淀粉酶”意指進(jìn)行變化以產(chǎn)生酶變體的α-淀粉酶。具有SEQIDNO:1或2的淀粉酶可以例如是所要求α-淀粉酶變體的親本。多核苷酸：如在此使用的術(shù)語“多核苷酸”或“編碼……的多核苷酸”是指編碼具有α-淀粉酶活性的成熟多肽的多核苷酸。所得變體：如在此使用的術(shù)語“所得變體”是指通過根據(jù)本發(fā)明的方法產(chǎn)生的變體，即所述變體包含任何一個或多個改變，如本文所述的取代和/或缺失。所得變體與術(shù)語“變體”、“根據(jù)本發(fā)明的變體”和本文類似地使用的其他術(shù)語具有相同的含義和目的，并因此是作為該生產(chǎn)方法的結(jié)果的變體。序列一致性：用參數(shù)“序列一致性”來描述兩個氨基酸序列之間或兩個核苷酸序列之間的相關(guān)性。出于本發(fā)明的目的，使用如在EMBOSS包(EMBOSS：歐洲分子生物學(xué)開放軟件套件，賴斯(Rice)等人，2000，遺傳學(xué)趨勢(TrendsGenet.)16:276-277)(優(yōu)選5.0.0版或更新版本)的尼德爾程序中所實(shí)施的尼德爾曼-翁施算法(尼德爾曼(Needleman)和翁施(Wunsch)，1970，分子生物學(xué)雜志(J.Mol.Biol.)48:443-453)來確定兩個氨基酸序列之間的序列一致性。所使用的參數(shù)是空位開放罰分10，空位延伸罰分0.5，以及EBLOSUM62(BLOSUM62的EMBOSS版本)取代矩陣。將標(biāo)記為“最長同一性”的Needle輸出(使用-nobrief選項(xiàng)獲得)用作百分比同一性并且是如下計(jì)算的：(一致的殘基X100)/(比對長度-比對中的空位總數(shù))變體：術(shù)語“變體”意指在一個或多個(例如，若干個)位置處包括改變(即，取代、插入和/或缺失)的具有α-淀粉酶活性的多肽。取代意指占據(jù)一個位置的氨基酸由不同的氨基酸代替；缺失意指除去占據(jù)一個位置的氨基酸；以及插入意指在占據(jù)一個位置的氨基酸的毗鄰處和緊鄰處添加一個氨基酸。本發(fā)明的變體具有SEQIDNO:1的成熟多肽的至少20％，例如至少40％、至少50％、至少60％、至少70％、至少80％、至少90％、至少95％或至少100％的α-淀粉酶活性。本發(fā)明的變體優(yōu)選地是SEQIDNO:1的親本α-淀粉酶的變體或與其具有至少90％一致性，如至少95％一致性的α-淀粉酶的變體。它們還可以是其他親本，如SEQIDNO:2、4、7、8、9、10、11、12、13、14、15或16的變體。非常高嚴(yán)格條件：術(shù)語“非常高嚴(yán)格條件”意指對于長度為至少100個核苷酸的探針而言，遵循標(biāo)準(zhǔn)DNA印跡程序，在42℃下在5XSSPE、0.3％SDS、200微克/ml剪切并變性的鮭魚精子DNA和50％甲酰胺中預(yù)雜交和雜交12至24小時。最后在70℃下使用2XSSC、0.2％SDS將載體材料洗滌三次，每次15分鐘。非常低嚴(yán)格條件：術(shù)語“非常低嚴(yán)格條件”是指對于長度為至少100個核苷酸的探針而言，遵循標(biāo)準(zhǔn)DNA印跡程序，在42℃下在5XSSPE、0.3％SDS、200微克/ml剪切并變性的鮭魚精子DNA和25％甲酰胺中預(yù)雜交和雜交12至24小時。最后在45℃下使用2XSSC、0.2％SDS將載體材料洗滌三次，每次15分鐘。野生型α-淀粉酶：術(shù)語“野生型”α-淀粉酶意指由天然存在的微生物(如在自然界中發(fā)現(xiàn)的細(xì)菌、古生菌、酵母或絲狀真菌)表達(dá)的α-淀粉酶。變體命名規(guī)則出于本發(fā)明的目的，使用在SEQIDNO:1中披露的成熟多肽來確定另一種α-淀粉酶中的相應(yīng)氨基酸殘基。將另一種α-淀粉酶的氨基酸序列與SEQIDNO:1中披露的成熟多肽進(jìn)行比對，并且基于該比對，使用如在EMBOSS包(EMBOSS：歐洲分子生物學(xué)開放軟件套件，賴斯(Rice)等人，2000，遺傳學(xué)趨勢(TrendsGenet.)16:276-277)(優(yōu)選5.0.0版或更新版本)的尼德爾程序中所實(shí)施的尼德爾曼-翁施算法(尼德爾曼(Needleman)和翁施(Wunsch)，1970，分子生物學(xué)雜志(J.Mol.Biol.)48:443-453)來確定與SEQIDNO:1中所披露的成熟多肽中的任何氨基酸殘基相對應(yīng)的氨基酸位置編號。所使用的參數(shù)是空位開放罰分10，空位延伸罰分0.5，以及EBLOSUM62(BLOSUM62的EMBOSS版本)取代矩陣?？梢酝ㄟ^使用若干計(jì)算機(jī)程序，使用其對應(yīng)默認(rèn)參數(shù)比對多個多肽序列來確定在另一種α-淀粉酶中的對應(yīng)氨基酸殘基的鑒定，所述計(jì)算機(jī)程序包括但不限于MUSCLE(通過對數(shù)-預(yù)期的多種序列比較；版本3.5或更新版本；埃德加(Edgar)，2004，核酸研究(NucleicAcidsResearch)32:1792-1797)、MAFFT(版本6.857或更新版本；加藤(Katoh)和庫馬(Kuma)，2002，核酸研究30:3059-3066；加藤等人，2005，核酸研究33:511-518；加藤和都(Toh)，2007，生物信息學(xué)(Bioinformatics)23:372-374；加藤等人，2009，分子生物學(xué)方法(MethodsinMolecularBiology)537:39-64；加藤和都，2010，生物信息學(xué)(Bioinformatics)26:1899-1900)以及采用ClustalW(1.83或更新版本；湯姆斯(Thompson)等人，1994，核酸研究(NucleicAcidsResearch)22:4673-4680)的EMBOSSEMMA。當(dāng)其他酶與SEQIDNO:1的成熟多肽相背離使得傳統(tǒng)的基于序列的比較方法不能檢測其相互關(guān)系時(林達(dá)爾(Lindahl)和埃洛弗松(Elofsson)，2000，分子生物學(xué)雜志(J.Mol.Biol.)295:613-615)，可應(yīng)用其他成對序列比較算法。在基于序列的搜索中的更大靈敏度可以使用搜索程序來獲得，這些搜索程序利用多肽家族的概率表示(譜(profile))來搜索數(shù)據(jù)庫。例如，PSI-BLAST程序通過迭代數(shù)據(jù)庫搜索過程來產(chǎn)生多個譜，并且能夠檢測遠(yuǎn)距離同源物(阿特休爾(Atschul)等人，1997，核酸研究(NucleicAcidsRes.)25:3389-3402)。當(dāng)多肽的家族或超家族在蛋白質(zhì)結(jié)構(gòu)數(shù)據(jù)庫中具有一個或多個代表時，甚至可達(dá)成更高的敏感度。程序如GenTHREADER(瓊斯(Jones)，1999，分子生物學(xué)雜志(J.Mol.Biol.)287:797-815；麥古芬(McGuffin)和瓊斯，2003，生物信息學(xué)(Bioinformatics)19:874-881)利用來自不同來源(PSI-BLAST、二級結(jié)構(gòu)預(yù)測、結(jié)構(gòu)比對譜以及溶劑化勢)的信息作為預(yù)測查詢序列的結(jié)構(gòu)折疊的神經(jīng)網(wǎng)絡(luò)的輸入。類似地，高夫(Gough)等人，2000，分子生物學(xué)雜志(J.Mol.Biol.)313:903-919的方法可以用于比對未知結(jié)構(gòu)的序列與存在于SCOP數(shù)據(jù)庫中的超家族模型。這些比對進(jìn)而可以用于產(chǎn)生多肽的同源性模型，并且使用出于該目的而開發(fā)的多種工具可以評定此類模型的準(zhǔn)確度。對于已知結(jié)構(gòu)的蛋白，若干工具和資源可用于檢索并產(chǎn)生結(jié)構(gòu)比對。例如，蛋白的SCOP超家族已經(jīng)在結(jié)構(gòu)上進(jìn)行比對，并且那些比對是可訪問的并且可下載的?？梢允褂枚喾N算法如距離比對矩陣(奧爾姆(Holm)和桑德(Sander)，1998，蛋白質(zhì)(Proteins)33:88-96)或組合延伸(辛迪亞洛夫(Shindyalov)和伯恩(Bourne)，1998，蛋白質(zhì)工程(ProteinEngineering)11:739-747)比對兩種或更多種蛋白質(zhì)結(jié)構(gòu)，并且這些算法的實(shí)施可以另外用于查詢具有感興趣結(jié)構(gòu)的結(jié)構(gòu)數(shù)據(jù)庫，以便發(fā)現(xiàn)可能的結(jié)構(gòu)同源物(例如，奧爾姆和帕克(Park)，2000，生物信息學(xué)(Bioinformatics)16:566-567)。在描述本發(fā)明的變體中，以下所述的命名法適于方便參考。采用了已接受的IUPAC單個字母和三字母的氨基酸縮寫。取代。對于氨基酸取代，使用以下命名法：初始氨基酸、位置、取代氨基酸。因此，在位置226處的蘇氨酸被丙氨酸取代表示為“Thr226Ala”或者“T226A”。在給定位置處的氨基酸可以被任何其他氨基酸取代的情況下，將其表示為T226A；C；D；E；F；G；H；I；K；L；M；N；P；Q；R；S；W；V；Y。因此，這意味著位置226處的蘇氨酸可以被選自A、C、D、E、F、G、H、I、K、L、M、N、P、Q、R、S、W、V或Y的組的一個氨基酸取代。同樣地，在給定位置處的氨基酸可以用選自特定的氨基酸組的一個氨基酸取代的情況下，例如在位置226處的蘇氨酸可以被酪氨酸、苯丙氨酸或組氨酸中的任一個取代的情況下，將其表示為T226Y；F；H。給定位置處的不同改變還可以由一個逗號分開，例如“Arg170Tyr,Glu”或“R170Y,E”代表位置170處的精氨酸被酪氨酸或谷氨酸取代。因此，“Tyr167Gly,Ala+Arg170Gly,Ala”命名了以下變體：“Tyr167Gly+Arg170Gly”、“Tyr167Gly+Arg170Ala”、“Tyr167Ala+Arg170Gly”以及“Tyr167Ala+Arg170Ala”。多個突變由加號(“+”)分開，例如“Gly205Arg+Ser411Phe”或“G205R+S411F”代表分別在位置205和位置411處甘氨酸(G)被精氨酸(R)取代，并且絲氨酸(S)被苯丙氨酸(F)取代。缺失。對于氨基酸缺失，使用以下命名法：初始氨基酸、位置、*。因此，在位置195處的甘氨酸缺失表示為“Gly195*”或“G195*”。多重缺失通過加號(“+”)分開，例如，“Gly195*+Ser411*”或“G195*+S411*”。插入。對于氨基酸插入，使用以下命名法：初始氨基酸、位置、初始氨基酸、插入氨基酸。因此，在位置195處的甘氨酸之后插入賴氨酸被表示為“Gly195GlyLys”或“G195GK”。多個氨基酸的插入被表示為[初始氨基酸，位置，初始氨基酸，插入氨基酸#1、插入氨基酸#2；等]。例如，在位置195處的甘氨酸之后插入賴氨酸和丙氨酸被表示為“Gly195GlyLysAla”或“G195GKA”。在此類情況下，通過將小寫字母添加至在所插入的一個或多個氨基酸殘基之前的氨基酸殘基的位置編號中來對所插入的一個或多個氨基酸殘基進(jìn)行編號。在以上實(shí)例中，該序列因此將是：親本：變體：195195195a195bGG-K-A多種改變。包含多種改變的變體由加號(“+”)分開，例如“Arg170Tyr+Gly195Glu”或者“R170Y+G195E”代表在位置170和位置195處的精氨酸和甘氨酸分別被酪氨酸和谷氨酸取代。術(shù)語“多重修飾”也可以在本文中使用。這樣的術(shù)語與“多種改變”具有相同的含義和目的，并且可以互換使用。發(fā)明詳細(xì)說明α-淀粉酶變體本發(fā)明涉及α-淀粉酶變體，該變體包括a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或三個或四個位置處的缺失和/或取代，以及b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在另一方面中，本發(fā)明涉及α-淀粉酶變體，該α-淀粉酶變體包括a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181+G182、R181+G184、G182+H183、或G182+G184的氨基酸位置處的成對缺失，以及b)在一個或多個位置處的取代，所述位置對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少70％，如至少75％、如至少80％、如至少85％、如至少90％、如至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個優(yōu)選的實(shí)施例中，b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在一個優(yōu)選的實(shí)施例中，a)是氨基酸H183+G184的缺失，并且b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在另一個實(shí)施例中，a)是氨基酸R181+G182的缺失，并且b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在另一個實(shí)施例中，a)是氨基酸R181+H183的缺失，并且b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在另一個實(shí)施例中，a)是氨基酸R181+G184的缺失，并且b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在另一個實(shí)施例中，a)是氨基酸G182+H183的缺失，并且b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在另一個實(shí)施例中，a)是氨基酸G182+G184的缺失，并且b)包括以下取代和/或缺失中的一種或多種：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R，其中*表示當(dāng)使用SEQIDNO:1進(jìn)行編號時的缺失。在另一個優(yōu)選的實(shí)施例中，b)包括以下取代和/或缺失的組合中的一種或多種：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E、G50A+R172Q+A204V、G50A+A51V+R172E+L173F+N174T+A204V、G50A+L173V、G50A+R172Q+L444P、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、G50A+A51V+R172Q、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、G50A+A51I+A204V、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、G50A+R172D+L173T、G50A+A51T+R172Q+L173F+N174Q、G50A+R172Q+N174Q+A204T、G50A+R172D+L173T+N174S、G50A+N174D+A204T、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、G50A+A51V+L173F+N174E+E471K、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、G50A+A51T+R172E+L173I、G50A+A51V+L173F+N174*、G50A+R172S+N174H、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、G50A+A51T+L173F+N174S、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+A51T+L173V+A204V、G50A+R172D+N174S、G50A+R172N、G50A+R172N+L173V、G50A+R172E+L173V+N174S、G50A+A51T+R172E+N174T、G50A+A51T+R172Q+L173I、G50A+R172E+L173T+N174S、G50A+A51T+R172E+A204V、G50A+R172E+N174T、G50A+R172N+A204T、G50A+R172Q+L173V、G50A+A51T+R172E、G50A+A51V+R172D+N174T、G50A+L173I+L173I+N174T+N174T+N219K+W220F、G50A+R172E+L173F+N174Q+A762、G50A+A51V+R172Q+N174Q、G50A+R172N+N174E、G50A+R172Q+L173T+N174Q、G50A+R172E+L173F+N174T、G50A+A51T+R172Q+L173V+A204V、G50A+A51T+R172D+L173F+N174T+K423P、G50A+R172E+L173F+N174Q+A204T、G50A+A113L+R172D+N174Q、G50A+R118D+W167F+R172D+N174Q、G50A+A51S+A113L+R118D+R172D+N174Q、G50A+R118D+R172D+N174Q、G50A+A51V+A113L+W167F+R172N+N174T+A204T、G50A+A51V+R118D+W167F+R172N+N174T+A204T、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+R118D+R172D+L173F、G50A+A51V+A113L+R118D+W167F+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+R118D+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51V+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+R118D+W167F+R172N+L173V、G50A+A51T+A113L+R118D+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R118D+R172N+L173V、G50A+A113L+W167F+R172Q+A1066、G50A+W167F+R172Q+A1105、G50A+R118D+R172Q、G50A+A113L+R118D+R172Q、G50A+A113L+W167F+172Q、G50A+R172D+L173F+E471K、G50A+A51T+R172D+E345D+E346P+D476G、G50A+R172D+N174Q+E345D+E346P+D476G、G50A+R172D+N174D+E345D+E346P+D476G、G50A+A51V+R172N+N174T+A204T+E345D+E346P+D476G、G50A+R172D+N174T+E345D+E346P+D476G、G50A+N174T+E345D+E346P+D476G、G50A+R172N+N174T+E345D+E346P+D476G、G50A+A51V+L173F+N174D+E345D+E346P+D476G、G50A+A51T+R172D+S255I+E345D+G477Q、G50A+A51V+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、G50A+R172D+N174Q+S255I+E345D+G477QG50A+R172D+N174D+S255I+E345D+G477Q、G50A+A51V+R172N+N174T+A204T+S255I+E345D、G50A+R172D+N174T+S255I+E345D+G477Q、G50A+R172N+N174T+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D、G50A+A51T+W140Y+P146S+R172D、G50A+A51T+W140Y+R172D、G50A+A51V+W140Y+R172E+L173F+N174T+A204V、G50A+W140Y+R172D+N174Q、G50A+W140Y+R172D+N174D、G50A+W140Y+P146S+R172D+N174D+E471K、G50A+A51V+W140Y+R172N+N174T+A204T、G50A+A51T+W140Y+R172N+L173V、G50A+W140Y+R172N+N174T、G50A+A51V+W140Y+P146S+L173F+N174D、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+Y206I+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51V+R172N+N174T+A204T+R320A+H321N+S323N、G50A+N174T+R320A+H321N+S323N、G50A+R172N+N174T+R320A+H321N+S323N、G50A+A51V+L173F+N174D+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+A113L+R172E+N174S+G304Q+E345D+E346T+V474T、G50A+A51T+A113L+R172E+N174S+G304V+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+Y206I+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+G149A+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V+R320A+S323N、G50A+A51T+W167F+R172N+L173V+Y206I+M208Y+V213S+V214T+L217M、G50A+A51T+W167F+R172N+L173V+Y206I+M208Y+V213T+V214T+L217M、A51V+R172D+L173F、A51V+R172Q+A204V、A51I+R172Q+L173F+A204T、A51V+L173I+N174S、A51T+L173T+N174S+A204T、W48L+A51T+R172Q+N174S+A204T、A51I+R172D、A51I+R172Q+N174E、A51I+R172E+N174T、A51V+R172Q+N174S+A204V、A51T+L173F+N174Q+A204V+A521、A51V+N174T+A204V、A51T+R172Q+L173T、A51T+R172N+A204V、A51L+R172N+N174S+A204T、A51T+R172N+L173*、A51T+R172Q、A51I+N174D、A51V+R172Q+L173F+N174S、A51T+R172D+N174Q、A51V+L173V+A204V、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51V+R172E+N174*、A51V+R172D、A51T+R172D+N174Q+G304Q+E345D+E346T+D476G+G477S、A51I+R172E+L173F、A51T+R172D+N174D、A51T+R172E+N174T、A51V+R172Q+L173T、A51V+N174Q+A204V、A51T+N174D+A204V、A51P+R172Q+N174D、A51T+R172N+A204V+G304Q+E345D+E346T+E391L+D476G+G477S、A51T+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476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S。在另一個優(yōu)選的實(shí)施例中，b)中的改變由以下改變的組合中的一種組成：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E、G50A+R172Q+A204V、G50A+A51V+R172E+L173F+N174T+A204V、G50A+L173V、G50A+R172Q+L444P、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、G50A+A51V+R172Q、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、G50A+A51I+A204V、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、G50A+R172D+L173T、G50A+A51T+R172Q+L173F+N174Q、G50A+R172Q+N174Q+A204T、G50A+R172D+L173T+N174S、G50A+N174D+A204T、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、G50A+A51V+L173F+N174E+E471K、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、G50A+A51T+R172E+L173I、G50A+A51V+L173F+N174*、G50A+R172S+N174H、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、G50A+A51T+L173F+N174S、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+A51T+L173V+A204V、G50A+R172D+N174S、G50A+R172N、G50A+R172N+L173V、G50A+R172E+L173V+N174S、G50A+A51T+R172E+N174T、G50A+A51T+R172Q+L173I、G50A+R172E+L173T+N174S、G50A+A51T+R172E+A204V、G50A+R172E+N174T、G50A+R172N+A204T、G50A+R172Q+L173V、G50A+A51T+R172E、G50A+A51V+R172D+N174T、G50A+L173I+L173I+N174T+N174T+N219K+W220F、G50A+R172E+L173F+N174Q+A762、G50A+A51V+R172Q+N174Q、G50A+R172N+N174E、G50A+R172Q+L173T+N174Q、G50A+R172E+L173F+N174T、G50A+A51T+R172Q+L173V+A204V、G50A+A51T+R172D+L173F+N174T+K423P、G50A+R172E+L173F+N174Q+A204T、G50A+A113L+R172D+N174Q、G50A+R118D+W167F+R172D+N174Q、G50A+A51S+A113L+R118D+R172D+N174Q、G50A+R118D+R172D+N174Q、G50A+A51V+A113L+W167F+R172N+N174T+A204T、G50A+A51V+R118D+W167F+R172N+N174T+A204T、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+R118D+R172D+L173F、G50A+A51V+A113L+R118D+W167F+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+R118D+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51V+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+R118D+W167F+R172N+L173V、G50A+A51T+A113L+R118D+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R118D+R172N+L173V、G50A+A113L+W167F+R172Q+A1066、G50A+W167F+R172Q+A1105、G50A+R118D+R172Q、G50A+A113L+R118D+R172Q、G50A+A113L+W167F+172Q、G50A+R172D+L173F+E471K、G50A+A51T+R172D+E345D+E346P+D476G、G50A+R172D+N174Q+E345D+E346P+D476G、G50A+R172D+N174D+E345D+E346P+D476G、G50A+A51V+R172N+N174T+A204T+E345D+E346P+D476G、G50A+R172D+N174T+E345D+E346P+D476G、G50A+N174T+E345D+E346P+D476G、G50A+R172N+N174T+E345D+E346P+D476G、G50A+A51V+L173F+N174D+E345D+E346P+D476G、G50A+A51T+R172D+S255I+E345D+G477Q、G50A+A51V+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、G50A+R172D+N174Q+S255I+E345D+G477QG50A+R172D+N174D+S255I+E345D+G477Q、G50A+A51V+R172N+N174T+A204T+S255I+E345D、G50A+R172D+N174T+S255I+E345D+G477Q、G50A+R172N+N174T+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D、G50A+A51T+W140Y+P146S+R172D、G50A+A51T+W140Y+R172D、G50A+A51V+W140Y+R172E+L173F+N174T+A204V、G50A+W140Y+R172D+N174Q、G50A+W140Y+R172D+N174D、G50A+W140Y+P146S+R172D+N174D+E471K、G50A+A51V+W140Y+R172N+N174T+A204T、G50A+A51T+W140Y+R172N+L173V、G50A+W140Y+R172N+N174T、G50A+A51V+W140Y+P146S+L173F+N174D、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+Y206I+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51V+R172N+N174T+A204T+R320A+H321N+S323N、G50A+N174T+R320A+H321N+S323N、G50A+R172N+N174T+R320A+H321N+S323N、G50A+A51V+L173F+N174D+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+A113L+R172E+N174S+G304Q+E345D+E346T+V474T、G50A+A51T+A113L+R172E+N174S+G304V+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+Y206I+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+G149A+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V+R320A+S323N、G50A+A51T+W167F+R172N+L173V+Y206I+M208Y+V213S+V214T+L217M、G50A+A51T+W167F+R172N+L173V+Y206I+M208Y+V213T+V214T+L217M、A51V+R172D+L173F、A51V+R172Q+A204V、A51I+R172Q+L173F+A204T、A51V+L173I+N174S、A51T+L173T+N174S+A204T、W48L+A51T+R172Q+N174S+A204T、A51I+R172D、A51I+R172Q+N174E、A51I+R172E+N174T、A51V+R172Q+N174S+A204V、A51T+L173F+N174Q+A204V+A521、A51V+N174T+A204V、A51T+R172Q+L173T、A51T+R172N+A204V、A51L+R172N+N174S+A204T、A51T+R172N+L173*、A51T+R172Q、A51I+N174D、A51V+R172Q+L173F+N174S、A51T+R172D+N174Q、A51V+L173V+A204V、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51V+R172E+N174*、A51V+R172D、A51T+R1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51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在另一個優(yōu)選的實(shí)施例中，a)是氨基酸H183+G184的缺失，并且b)中的改變包括以下改變的組合中的一種：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E、G50A+R172Q+A204V、G50A+A51V+R172E+L173F+N174T+A204V、G50A+L173V、G50A+R172Q+L444P、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、G50A+A51V+R172Q、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、G50A+A51I+A204V、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、G50A+R172D+L173T、G50A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E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在另一個優(yōu)選的實(shí)施例中，a)是氨基酸R181+G182的缺失，并且b)中的改變包括以下改變的組合中的一種：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E、G50A+R172Q+A204V、G50A+A51V+R172E+L173F+N174T+A204V、G50A+L173V、G50A+R172Q+L444P、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、G50A+A51V+R172Q、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、G50A+A51I+A204V、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、G50A+R172D+L173T、G50A+A51T+R172Q+L173F+N174Q、G50A+R172Q+N174Q+A204T、G50A+R172D+L173T+N174S、G50A+N174D+A204T、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、G50A+A51V+L173F+N174E+E471K、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、G50A+A51T+R172E+L173I、G50A+A51V+L173F+N174*、G50A+R172S+N174H、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、G50A+A51T+L173F+N174S、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+A51T+L173V+A204V、G50A+R172D+N174S、G50A+R172N、G50A+R172N+L173V、G50A+R172E+L173V+N174S、G50A+A51T+R172E+N174T、G50A+A51T+R172Q+L173I、G50A+R172E+L173T+N174S、G50A+A51T+R172E+A204V、G50A+R172E+N174T、G50A+R172N+A204T、G50A+R172Q+L173V、G50A+A51T+R172E、G50A+A51V+R172D+N174T、G50A+L173I+L173I+N174T+N174T+N219K+W220F、G50A+R172E+L173F+N174Q+A762、G50A+A51V+R172Q+N174Q、G50A+R172N+N174E、G50A+R172Q+L173T+N174Q、G50A+R172E+L173F+N174T、G50A+A51T+R172Q+L173V+A204V、G50A+A51T+R172D+L173F+N174T+K423P、G50A+R172E+L173F+N174Q+A204T、G50A+A113L+R172D+N174Q、G50A+R118D+W167F+R172D+N174Q、G50A+A51S+A113L+R118D+R172D+N174Q、G50A+R118D+R172D+N174Q、G50A+A51V+A113L+W167F+R172N+N174T+A204T、G50A+A51V+R118D+W167F+R172N+N174T+A204T、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+R118D+R172D+L173F、G50A+A51V+A113L+R118D+W167F+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+R118D+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51V+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+R118D+W167F+R172N+L173V、G50A+A51T+A113L+R118D+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R118D+R172N+L173V、G50A+A113L+W167F+R172Q+A1066、G50A+W167F+R172Q+A1105、G50A+R118D+R172Q、G50A+A113L+R118D+R172Q、G50A+A113L+W167F+172Q、G50A+R172D+L173F+E471K、G50A+A51T+R172D+E345D+E346P+D476G、G50A+R172D+N174Q+E345D+E346P+D476G、G50A+R172D+N174D+E345D+E346P+D476G、G50A+A51V+R172N+N174T+A204T+E345D+E346P+D476G、G50A+R172D+N174T+E345D+E346P+D476G、G50A+N174T+E345D+E346P+D476G、G50A+R172N+N174T+E345D+E346P+D476G、G50A+A51V+L173F+N174D+E345D+E346P+D476G、G50A+A51T+R172D+S255I+E345D+G477Q、G50A+A51V+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、G50A+R172D+N174Q+S255I+E345D+G477QG50A+R172D+N174D+S255I+E345D+G477Q、G50A+A51V+R172N+N174T+A204T+S255I+E345D、G50A+R172D+N174T+S255I+E345D+G477Q、G50A+R172N+N174T+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D、G50A+A51T+W140Y+P146S+R172D、G50A+A51T+W140Y+R172D、G50A+A51V+W140Y+R172E+L173F+N174T+A204V、G50A+W140Y+R172D+N174Q、G50A+W140Y+R172D+N174D、G50A+W140Y+P146S+R172D+N174D+E471K、G50A+A51V+W140Y+R172N+N174T+A204T、G50A+A51T+W140Y+R172N+L173V、G50A+W140Y+R172N+N174T、G50A+A51V+W140Y+P146S+L173F+N174D、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+Y206I+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51V+R172N+N174T+A204T+R320A+H321N+S323N、G50A+N174T+R320A+H321N+S323N、G50A+R172N+N174T+R320A+H321N+S323N、G50A+A51V+L173F+N174D+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+A113L+R172E+N174S+G304Q+E345D+E346T+V474T、G50A+A51T+A113L+R172E+N174S+G304V+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+Y206I+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+G149A+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V+R320A+S323N、G50A+A51T+W167F+R172N+L173V+Y206I+M208Y+V213S+V214T+L217M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476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D476K+G477A、G50A+R172N+A204T+E346T+D432A+D476K+G477A、G50A+R172N+A204T+E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在另一個優(yōu)選的實(shí)施例中，a)是氨基酸R181+H183的缺失，并且b)中的改變包括以下改變的組合中的一種：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I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、G50A+R172D+N174Q+E345D+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、G50S+R172N+N174Q+E345D+E346P+D476G、R172N+N174Q+E345D+D406A+I411M+N446K、G50S+R172N+N174Q+E345D、G50A+N174D+A204T+E345D+D476K+G477S、G50A+N174D+A204T+S255I+E345D+G477Q、G50A+N174D+A204T+G304S+E345D+D476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D476K+G477A、G50A+R172N+A204T+E346T+D432A+D476K+G477A、G50A+R172N+A204T+E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在另一個優(yōu)選的實(shí)施例中，a)是氨基酸R181+G184的缺失，并且b)中的改變包括以下改變的組合中的一種：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E、G50A+R172Q+A204V、G50A+A51V+R172E+L173F+N174T+A204V、G50A+L173V、G50A+R172Q+L444P、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、G50A+A51V+R172Q、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、G50A+A51I+A204V、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、G50A+R172D+L173T、G50A+A51T+R172Q+L173F+N174Q、G50A+R172Q+N174Q+A204T、G50A+R172D+L173T+N174S、G50A+N174D+A204T、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、G50A+A51V+L173F+N174E+E471K、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、G50A+A51T+R172E+L173I、G50A+A51V+L173F+N174*、G50A+R172S+N174H、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、G50A+A51T+L173F+N174S、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+A51T+L173V+A204V、G50A+R172D+N174S、G50A+R172N、G50A+R172N+L173V、G50A+R172E+L173V+N174S、G50A+A51T+R172E+N174T、G50A+A51T+R172Q+L173I、G50A+R172E+L173T+N174S、G50A+A51T+R172E+A204V、G50A+R172E+N174T、G50A+R172N+A204T、G50A+R172Q+L173V、G50A+A51T+R172E、G50A+A51V+R172D+N174T、G50A+L173I+L173I+N174T+N174T+N219K+W220F、G50A+R172E+L173F+N174Q+A762、G50A+A51V+R172Q+N174Q、G50A+R172N+N174E、G50A+R172Q+L173T+N174Q、G50A+R172E+L173F+N174T、G50A+A51T+R172Q+L173V+A204V、G50A+A51T+R172D+L173F+N174T+K423P、G50A+R172E+L173F+N174Q+A204T、G50A+A113L+R172D+N174Q、G50A+R118D+W167F+R172D+N174Q、G50A+A51S+A113L+R118D+R172D+N174Q、G50A+R118D+R172D+N174Q、G50A+A51V+A113L+W167F+R172N+N174T+A204T、G50A+A51V+R118D+W167F+R172N+N174T+A204T、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+R118D+R172D+L173F、G50A+A51V+A113L+R118D+W167F+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+R118D+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51V+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+R118D+W167F+R172N+L173V、G50A+A51T+A113L+R118D+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R118D+R172N+L173V、G50A+A113L+W167F+R172Q+A1066、G50A+W167F+R172Q+A1105、G50A+R118D+R172Q、G50A+A113L+R118D+R172Q、G50A+A113L+W167F+172Q、G50A+R172D+L173F+E471K、G50A+A51T+R172D+E345D+E346P+D476G、G50A+R172D+N174Q+E345D+E346P+D476G、G50A+R172D+N174D+E345D+E346P+D476G、G50A+A51V+R172N+N174T+A204T+E345D+E346P+D476G、G50A+R172D+N174T+E345D+E346P+D476G、G50A+N174T+E345D+E346P+D476G、G50A+R172N+N174T+E345D+E346P+D476G、G50A+A51V+L173F+N174D+E345D+E346P+D476G、G50A+A51T+R172D+S255I+E345D+G477Q、G50A+A51V+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、G50A+R172D+N174Q+S255I+E345D+G477QG50A+R172D+N174D+S255I+E345D+G477Q、G50A+A51V+R172N+N174T+A204T+S255I+E345D、G50A+R172D+N174T+S255I+E345D+G477Q、G50A+R172N+N174T+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D+G477Q、G50A+A51V+L173F+N174D+S255I+E345D、G50A+A51T+W140Y+P146S+R172D、G50A+A51T+W140Y+R172D、G50A+A51V+W140Y+R172E+L173F+N174T+A204V、G50A+W140Y+R172D+N174Q、G50A+W140Y+R172D+N174D、G50A+W140Y+P146S+R172D+N174D+E471K、G50A+A51V+W140Y+R172N+N174T+A204T、G50A+A51T+W140Y+R172N+L173V、G50A+W140Y+R172N+N174T、G50A+A51V+W140Y+P146S+L173F+N174D、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+Y206I+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51V+R172N+N174T+A204T+R320A+H321N+S323N、G50A+N174T+R320A+H321N+S323N、G50A+R172N+N174T+R320A+H321N+S323N、G50A+A51V+L173F+N174D+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+A113L+R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74T+A204V+K302Q+E346P+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、G50A+A51V+R172N+N174T+A204T+K302Q+E346P+D476K+G477S、G50A+A51V+R172N+N174T+A204T+E345D+D476K+G477S、N174D+A204T+K302Q+E346P+D476K+G477S、G50A+R172D+N174Q+K302Q+E346P+D476K+G477S、G50A+R172D+N174Q+E345D+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、G50S+R172N+N174Q+E345D+E346P+D476G、R172N+N174Q+E345D+D406A+I411M+N446K、G50S+R172N+N174Q+E345D、G50A+N174D+A204T+E345D+D476K+G477S、G50A+N174D+A204T+S255I+E345D+G477Q、G50A+N174D+A204T+G304S+E345D+D476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D476K+G477A、G50A+R172N+A204T+E346T+D432A+D476K+G477A、G50A+R172N+A204T+E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在另一個優(yōu)選的實(shí)施例中，a)是氨基酸G182+G184的缺失，并且b)中的改變包括以下改變的組合中的一種：H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A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51V+K72R+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51V+W140Y+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51T+R172N+L173V+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+K302Q+E346P+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、G50A+A51V+R172N+N174T+A204T+K302Q+E346P+D476K+G477S、G50A+A51V+R172N+N174T+A204T+E345D+D476K+G477S、N174D+A204T+K302Q+E346P+D476K+G477S、G50A+R172D+N174Q+K302Q+E346P+D476K+G477S、G50A+R172D+N174Q+E345D+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、G50S+R172N+N174Q+E345D+E346P+D476G、R172N+N174Q+E345D+D406A+I411M+N446K、G50S+R172N+N174Q+E345D、G50A+N174D+A204T+E345D+D476K+G477S、G50A+N174D+A204T+S255I+E345D+G477Q、G50A+N174D+A204T+G304S+E345D+D476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D476K+G477A、G50A+R172N+A204T+E346T+D432A+D476K+G477A、G50A+R172N+A204T+E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V+D476Y、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+R172E+A204T+K302Q+E346P+D476K+G477S、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)A洗滌劑中在15℃的溫度下測定時，所述變體具有至少1.1的改進(jìn)因子(IF)。在一優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：Y363L、Y160L、W167L、W167F、K72S、K72R、T40K、T40M、H1*+H2*+G7S、Q361S、Q361A、E345S、E276S、W268F、V291A、V56A、V56T、R171E、K302A、L429A、A354V、K347M、K347A、N270Y+Y295N+N299T、Y295N+N299T、A113Y+R171E、T40K+K179S,H1L+R171E+D192E、T40K+R171E、R171E+H324L+Q361A+Y363L、R171E+Q361A+Y363L、A113Y+R171E+E391L、R171E+D192E+Y363L、A113Y+R171E+Y363L+E391L+K423P、408H、K423N、I430M、W140Y、R320A、W140Y+R320A、R172Y、A113N、R142K、R172L、R172LR172S、A113Y、A113L、R142S、R172P、R172T、R172V、R172A、L173V、N174Y、N174G、Y243E、Y243S、Y243G、Y243D、V165G、Y243T、P211D、K269L、K269N、K269I、K269V、K269M、E391A、E391M、K179S、E391L、E391H、K179A、K179T、H1G、H1S、H1L、K423L、K423H、K423P、K423T、L217F、K302R、N296Q、H1N、N197A、V165M、D192A、D192E、N281Q、N281S、V165A、V165G、M208S、A186M、H321A、H324R、H324W、S323E、N128T、T193G、T193A、T193N、H1*+H2E、H1*+H2V、Q280S、H1*+H2A、G304V、I430E、G149Q、G149A、Q169G、Q169M、N215A、N311L、L351C、N215G、L351H、N311E、N219S、N219E、N219T、H1*+N3C、A274T、L351S、G182A+V213T+V214S、H210S、H210Y、P211T、P211T+V213T,G182N+V213S、H210S+V214T、P211T、V213T+V214S、K269Q+A274W、K269H+A274E、K269Q+A274Y、K269Q+A274L、K269Q+A274M、K269Q+A274S、K269Q+A274G、K269V+A274Y、K269L+A274G、K269L+A274W、K269Q+A274R、K269R+A274G、K269H+A274C、R172Q+N174Q、R172Q+N174S、R172Q+L173F+N174Y、G50A+A51T+N174E、R172N、R172Q+N174T+A204T、N174S、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、R172K+L173I+N174S、G50A+A51V+R172N+N174S、R172Q+L173F+A204T、G50A+A51T+R172Q、G50A+R172Q+N174T、R172Q+N174T、G50A+R172Q+N174D、N174D+A204V、G50A+R172N+N174S、G50A+R172N+N174T、G73V+R172Q+N174E、R172N+L173T+N174Q+S303R、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、R172Q、L173T+N174Q+A204V、R172K+L173F、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+A51T+R172Q+L173V、G50A+R172D+N174D、G50A+R172D+N174Q、R172D+N174T、G50A+A51V+R172N+N174T+A204T、R172E、G304Q+E346P+D476K+G477A、E346P+G477Q、E346P+G477T、G304S+E345D+E346P+D476K+G477Q、E346P+D476Q+G477T、E346P+D476K+G477S、E345D+D476K+G477S、E346T+D476K+G477A、E345D+E346P+D476G、K302Q+E346P+D476K+G477S、G304A+E345D+E346P+D476G+G477K、G304Q+E346P+D476G、E346P+D476G+G477K、G304A+E346P+D476K+G477A、K302N+E345D+D476Q+G477Q、G304A+D476K+G477S、E345D+E346P+G477Q、L173F+N174Q、R172Q+L173F、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、R172D+L173F、R172D、A51V+R172Q+A204V、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、L173F、T136N+R172Q+N174D+A204T、G50A+R172Q+A204V、G50A+R172N+A204T、A51T+L173T+N174S+A204T、L173I+N174D、W48L+A51T+R172Q+N174S+A204T、G50A+A51V+R172E+L173F+N174T+A204V、G50A+R172Q+L444P、R172Q+L173T+N174S、L173F+A204T、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、R172Q+L173F+N174D、G50A+A51V+R172Q、R172Q+N174*、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、L173V+N174T、N174T、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、A51I+R172E+N174T、G50A+A51I+A204V、R172Q+N174D、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、A274E+G304Q+G305S+E345D+D476K+G477Q、E346P+D476Q+G477S、E345D+E346P+D476G+G477T、E346T+D476K、E345D+D476Q+G477K、G304Q+E345D+E346T+D476G+G477S、E346T、G305S+E346T+D476Q+G477Q、E345D+E346T+D476Q+G477Q、K302Q+E345D+E346P+D476K+G477Q、E346T+G477K、E346P+G477S、K302Q+E346P+D476K+G477Q、G304A+E346P+D476G+G477A、E345D+D476Q+G477S、G304S+E346P+D476K+G477S、G304A+E345D+E346T+D476Q+G477Q、E346T+D476Q+G477A、R118L、R118S+G182A+T193K、R118P+G182A、R118P+G182S、R118S+E134D、E134D+K179L+G182N、R118S、R118S+G182A、R118S+N128L+G182S、G182S+A186V、R118D+K179L+G182A、R118P+G182N、R118S+E134D+G182S、E134D+A186E、N128F+K179L、N128Q+K179L+A186S、R118D、G304Q+E346P+D476G+G477S、E345D+D476G+G477S、D476K+G477Q、G304A+E345D+D476Q+G477Q、R172E+L173T+N174T、G50A+A51V+L173F+N174D、G50A+R172D+L173T、A51V+R172Q+N174S+A204V、G50A+R172D+L173T+N174S、G50A+N174D+A204T、R172Q+L173V、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、R172Q+L173F+N174D+A204T、G50A+A51T+R172Q+A204V、R172E+L173F+N174D、A51V+N174T+A204V、R172K+A204V、A51T+R172Q+L173T、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、A51T+R172N+A204V、G50A+A51T+R172E+L173I、N174Q+A204V、G50A+A51V+L173F+N174*、R172E+N174D+A204T、A51T+R172N+L173*、R172N+L173F+N174Q+V489G、R172E+L173F、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、A51T+R172Q、G50A+R172E+L173F+N174D、G67E+D112N+R172D+L173F+N174S+S466F、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、R172Q+L173V+A204T、A51V+R172Q+L173F+N174S、A51T+R172D+N174Q、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、A51V+L173V+A204V、G149Q+R171E、A113Y+G149Q+R171E+D192E+Q280S、H1L+A113Y+R171E+D192E、R171E+D192E+Q280S+Q361A+Y363L+E391L+K423P、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、R172Q+N174D+G304Q+E345D+E346T+D476G+G477S、K302N+E346T+D476Q+G477T、K302Q+D476G+G477A、S255I+E345D+G477Q、E346T+G477A、K302Q+E346P+D476K+G477A、G304A+E345D+E346P+D476Q+G477S、A47G+G67E+A111T+D112H+R245L+E346P+D476G+G477T、G304A+E346T+D476K+G477T、G304S+E345D+D476K+G477Q、K302N+E345D+D476G、A113T+G304S+E345D+E346P+D476G+G477Q、R320S+H324Q、R320S+S323M、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、Q98A+R320A+S323N、Q98T+R320A+H324L、G7E+Q98T+R320A、G7L+R320S+S323M+V489G、G7D+Q98A+R320M、G7E+Q98A+R320M、R320A+S323N、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7Q+R320S+S323M、Q98A+A265S+R320A、G7N+R320A、Q98N+R320A+S323N、R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、R320A+H324L、G7K+R320M+H321Q、R320S+S323N、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、R320A+H324Q、G304A+E346P+D476Q+G477T、K302Q+E346P+D476K、K302Q+E346P+G477Q、K302Q+D476G+G477Q、G304A+E345D+D476Q、E345D+E346P+D476Q+G477S、G304Q+E345D+E346T、E345D+E346T+D476G+G477S、V75I+R320A+S323N、G7X+Q98T+R320A、R320T、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、A87D+R320S+S323M、R320S+S323M+H324L、Q98K+K269N+R320A+S323M+H324Q、G7K+R320A+P408Q、G7K+R320A+H324L、R320A+H321W+S323M+H324Q、G7L+R320M+S323N、N2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432A+D476K+G477A、G50A+R172N+A204T+E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+E416K+K438N、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51V+R172N+N174T+A204T+R320V+D476Y、G50A+A51V+R172N+N174T+A204T+R320V、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172N+L173V+R320V+D476Y、G50A+A51T+R172D+R320A+S323N、G50A+R172Q+L173T+E346T+G477A、R172Q+L173T+R320V+D476Y、N174D+A204T+R320V+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51V+N174S+R320V+D476Y、A51V+N174S+R320V+D476Y、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+D476Y、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+R172D+N174Q+A204V+R320A+S323N、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、R172D+N174E+M208Y+V213S+V214T+L217M、,G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+E345D+E346P+D476G、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、G7K+T40K+W167F+R320A+S323N+P364S、G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)A洗滌劑中在15℃的溫度下測定時，所述變體具有至少1.3的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：W167F、K72S、K72R、T40K、T40M、H1*+H2*+G7S、E345S、V291A、V56A、V56T、R171E、A354V、A113Y+R171E、H1L+R171E+D192E、T40K+R171E、R171E+H324L+Q361A+Y363L、R171E+Q361A+Y363L、A113Y+R171E+E391L、A113Y+R171E+Y363L+E391L+K423P、W140Y、W140Y+R320A、R172Y、R142K、R172S、A113Y、A113L、R172T、R172V、Y243E、Y243S、Y243G、Y243D、V165G、P211D、K269M、K179S、E391H、K179T、V165M、V165G、T193G、Q169M、N215G、G50A+A51T+N174E、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+R172Q+N174T、R172Q、L173T+N174Q+A204V、E346T+D476K+G477A、E345D+E346P+D476G、K302Q+E346P+D476K+G477S、G304A+E345D+E346P+D476G+G477K,R172Q+L173F、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+A51V+R172D+L173F、G50A+A51V+R172D+L173F+N174Q+A204T、G50A+A51V+R172E+L173F+N174T+A204V、G50A+A51T+R172N+L173V、R172Q+L173F+N174D、G50A+R172E+L173F、L173V+N174T、N174T、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、A51I+R172E+N174T、G50A+A51I+A204V、R172Q+N174D、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、A274E+G304Q+G305S+E345D+D476K+G477Q、E346P+D476Q+G477S、G304Q+E345D+E346T+D476G+G477S、E346T、R118S+G182A+T193K、R118P+G182A、R118P+G182S、R118S+E134D、R118D+K179L+G182A、N128Q+K179L+A186S、R118D、G304Q+E346P+D476G+G477S、G50A+R172D+L173T、R172Q+L173V、G50A+A51T+R172N+L173I+N174Q、R172E+L173F+N174D、R172K+A204V、A51T+R172Q+L173T、G50A+A51Q+R172Q、G50A+A51T+R172E+L173I、R172E+N174D+A204T、A51T+R172N+L173*、G50A+A51T+A87S+R172N+L173T+N174D、G67E+D112N+R172D+L173F+N174S+S466F、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、R172Q+L173V+A204T、A51T+R172D+N174Q、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、R171E+D192E+Q280S+Q361A+Y363L+E391L+K423P、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、K302Q+D476G+G477A、S255I+E345D+G477Q、G304S+E345D+D476K+G477Q、A113T+G304S+E345D+E346P+D476G+G477Q、G7Q+Q98S+R320S+H324Q、R320A+S323N、G7L+P211Q+S303G+R320A、G7Q+R320A+S323N、G7K+R320M+H321Q、R320S+S323N、G7X+Q98T+R320A、R320T、Q98K+K269N+R320A+S323M+H324Q、G7K+R320A+P408Q、G7L+R320M+S323N、N28S+R320M+S323N、T5*+G4*+N3*+R320A,G7E+R142I+R320A+E391K+A392P+R393*+Q394S、G7L+R320A+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、R320A+H321N+S323N,G7Q+Q98T+R320A+S323M、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、A51T+R172D+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+R172N+L173V、A51V+R172D、R172E+N174T、G50A+A51T+R172E+N174T、R172D+L173V+N174D、G50A+A51T+R172Q+L173I、R172Q+N174E、R172E+L173I+A204T、A51T+R172D+N174D、R172E+L173T+N174S+A204T、L173T+N174T+A204V、R172N+N174D、G50A+R172E+L173F+N174Q、G50A+R172N+N174E、R172K+L173V+N174S+A204T+L429F、R172D+L173V、R172D+L173I+N174S、A51V+R172Q+L173T、G50A+A51T+R172Q+L173V+A204V、R172N+L173I、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T,G50A+A113L+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R118D+R172N+L173V、R118D+W167F+R172Q+N174D、R118D+R172Q+N174D、W167F+R172Q+N174D、A204T+G304Q+E345D+E346T+D476G+G477S、R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、A113L+W167F+R172Q+Y363L、T40K+G50A+R172Q+I430E、T40K+K72R+W167F、W167F+R172Q+E346T+Y363L、K72R+A113L+W167F+R172Q+N215G+Y363L、S255I+R320A+H321N+S323N+E345D+G477Q、G50A+A113L+W167F+R172Q、G50A+W167F+R172Q、G50A+A113L+R118D+R172Q,G50A+A113L+W167F+R172Q、G50A+R172D+L173F+E471K、G50A+A51T+R172D+S255I+E345D+G477Q、G50A+R172D+N174Q+S255I+E345D+G477Q、R171E+D192E+S255I+E345D+G477Q、G50A+R172D+N174D+S255I+E345D+G477Q、G50A+R172D+N174T+S255I+E345D+G477Q、G50A+A51T+W140Y+R172D、G50A+A51V+W140Y+R172E+L173F+N174T+A204V、G50A+W140Y+R172D+N174Q、G50A+A51T+W140Y+R172N+L173V、W140Y+R172D+N174T、A113L+R118D+W167F+S255I+E345D+G477Q、K72R+A113L+S255I+E345D+G477Q、K72R+A113L+W167F+S255I+E345D+G477Q、R118D+W167F+S255I+E345D+G477Q、Q98N+M208Y+V213T+V214T+L217M+R320A+S323M、R172E+N174D+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、R172E+N174D+A204T+G304Q+E345D+E346T+E391L、R172E+N174D+A204T+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51V+L173F+N174D+R320A+H321N+S323N、W167F+E345D+D476K+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+G149A+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V+R320A+S323N、G50A+A51T+W167F+R172N+L173V+M208Y+V213S+V214T+L217M、V165G、G50A+A51I+R172D+L173V、R172D+L173T+N174D+A204T、G50A+R172E+N174S、R172D+L173T+N174D、G50A+A51T+R172N+A204T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+D476K+G477A、T40K+K72R+Q98N+R320A+S323M、T40K+K72R+A113L+W167F、T40K+G50A+W167F+R172N+N174S+A204T、K72R+W167F+E346T+D476K+G477A+Y482F、G50A+A51V+K72R+W167F+R172E+L173F+N174T+A204V、T40K+G50A+A51V+K72R+W167F+R172E+L173F+N174T+A204V、T40K+G50A+A51V+R172N+N174T+A204T、T40K+G50A+A51V+W167F+R172N+N174T+A204T、T40K+G50A+A51V+K72R+R172N+N174T+A204T、T40K+K72R+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S,T40K+K72R+W167F+R172N+L173、+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+N174T+E346T+D476K+G477A,A51V+R172D+N174S+G305N+G465L+D467G、G50A+A51V+R172D+L173F+A204V+K302Q+D476G+G477S、G50A+A51V+L173Q+R172*+N174T+G305S+E346P+G477T、R172D+L173F+N174D+E345D+E346P+W469L、T40K+K72R+W167F+N174D+A204T、W140Y+W167F+N174D、G50A+W140Y+W167F+N174D+A204T、T40K+K72R+W167F+R172K+A204V、T40K+W167F+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、T40K+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、W140Y+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、A51T+W140Y+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172N+A204T、T40K+G50A+R172N+A204T、G50A+W140Y+R172N+A204T、G50A+W140Y+W167F+R172N+A204T、W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、W140Y+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、T40K+G50A+K72R+W167F+R172D+N174T+E345D+G477Q、G50A+W140Y+R172D+N174T+E345D+E346P+D476G、G50A+W140Y+W167F+R172D+L173F+N174T+G304Q+E345D+E346P+D476G、T40K+K72R+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、T40K+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、T40K+K72R+Q98N+W167F+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+V474I、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+R415K、Q98N+W140Y+W167F+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D、G50A+A51V+W140Y+P146S+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W140Y+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51T+R172N+L173V+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、G50A+A51V+R172N+N174T+A204T+E345D+D476K+G477S、G50A+R172D+N174Q+E345D+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、R172N+N174Q+E345D+D406A+I411M+N446K、G50S+R172N+N174Q+E345D、G50A+N174D+A204T+S255I+E345D+G477Q、G50A+N174D+A204T+G304S+E345D+D476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q,R172K+A204V+E345D+D476K、G50A+R172N+A204T+E346T+D476K+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+K302Q+E346P+D476K、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、R172K+A204V+M208Y+V213T+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320V、G50A+A51T+R172E+A204T+E346T+G477A、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、R172D+N174Q+A204V+E346T+G477A、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+W167F+S255I+E345D+G477Q、G50A+A51T+R172E+A204T+E346T+D476K+G477A、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+S255I+E345D+G477Q、G50A+R172D+N174Q+A204V+R320A+S323N、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、L173T+G184S+A204T、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、R172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172N+L173V+K302Q+E346P+D476K+G477S、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+R320A+H321N+S323N、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+R172D+N174D+E346T+D476K、G50A+R172N+N174T+E346T+D476K、R118P+W140Y、G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)A洗滌劑中在15℃的溫度下測定時，所述變體具有至少1.5的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：V291A、V56T、R171E、R172S、R172T、R172V、G50A+R172E+L173F、L173V+N174T、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、G50A+A51I+A204V、R172Q+N174D、G50A+R172E+L173V+N174T、G50A+A51T+L173F、G304Q+E345D+E346T+D476G+G477S、E346T、R118P+G182A、N128Q+K179L+A186S、R118D、G50A+A51Q+R172Q、R172E+N174D+A204T、A51T+R172D+N174Q、G7L+R320A+S323M、G7K+R320A+S323N+P364S、G7H+Q98S+R320A+S323M+H324L、R320A+H321N+S323N、R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、R172D+L173V+N174D、R172Q+N174E、R172E+L173T+N174S+A204T、G50A+R172E+L173F+N174Q、G50A+A51T+R172Q+L173V+A204V、R118D+W167F+R172Q+N174D、R118D+R172Q+N174D、R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、A113L+W167F+R172Q+Y363L、T40K+G50A+R172Q+I430E、W167F+R172Q+E346T+Y363L、G50A+A113L+W167F+R172Q、G50A+W167F+R172Q、G50A+A51T+W140Y+R172D、R172E+N174D+A204T+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、T40K+G50A+A51V+K72R+R172N+N174T+A204T、W140Y+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172N+A204T、G50A+W140Y+R172N+A204T、T40K+G50A+K72R+W167F+R172D+N174T+E345D+G477Q、T40K+G50A+A51V+W167F+R172D+N174E、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、Y243D、V165G、R118S+E134D、G50A+A51T+W167F+R172N+L173V、A113L+R118D+W167F+S255I+E345D+G477Q、G50A+A51I+R172D+L173V、W140Y+W167F+N174D、T40K+W167F+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、A51T+W140Y+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+W140Y+W167F+R172N+A204T、W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、G50A+W140Y+W167F+R172D+L173F+N174T+G304Q+E345D+E346P+D476G、T40K+K72R+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、G50A+A51V+W140Y+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、R172D+N174T+K302Q+E346P+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、L173T+A204T+E346T+G477A、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G7Q+T40K+K72R+W167F、R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、R172E+L173F+N174D+R320A+S323N、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)A洗滌劑中在40℃的溫度下測定時，所述變體具有至少1.1的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G7K+T40K+K72R+W167F、W140Y+W167F+A204V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、G50A+L173T+A204T+K302Q+E346P+D476K+G477S、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G,R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+N174S+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、R172N+L173V+E346T+D476K+G477A,R172N+L173V+E345D+E346P+D476G、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+E346T、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、G50A+R172N+N174T+E346T+D476K，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)A洗滌劑中在40℃的溫度下測定時，所述變體具有至少1.3的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：T40K、V56T、R171E、A113Y、K269L、K269M、E391A、E391L、H1L、H324L、G149A、K269Q+A274S、L173F、T136N+R172Q+N174D+A204T、G50A+R172E、E345D+E346T+D476Q+G477A、G50A+R172D+N174T+E345D+E346P+D476G、G50A+N174T+E345D+E346P+D476G、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D476K+G477A、G50A+R172N+A204T+E346T+D432A+D476K+G477A、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51T+R172E+A204T+E346T+D476K+G477A、R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174D+R320A+S323M+A442V+D476Y，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)J洗滌劑中在15℃的溫度下測定時，所述變體具有至少1.1的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，a)該變體包括對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：Y363L、Y160H、Y160L、W167L、W167F、Q169K、K72S、K72R、T40K、T40M、H1*+H2*+G7S、Q361S、Q361A、E345S、W268F、V291A、V56A、V56T、R171E、R171S、K302A、L351A、L429A、A354V、K347M、K347A、K483R、T282G、N270Y+Y295N、A113Y+R171E、T40K+K179S、R171E+E391L、R171E+Y363L、H1L+R171E+D192E、T40K+R171E、R171E+H324L+Q361A+Y363L、R171E+Q361A+Y363L、R171E+D192E+Y363L、A113Y+R171E+Y363L+E391L+K423P、K423N、I430M、R158A、W140Y、R320A、W140Y+R320A、R172Y、R142K、R172L、R172L、R172S、A113Y、A113L、R172T、R172V、R172A、L173V、Y243E、Y243F、Y243S、Y243G、Y243D、V165G、Y243T、N299K、P211D、K269L、K269N、K269I、K269V、K269M、R118G、R118P、K179M、E391A、E391M、K179S、E391L、E391K、E391H、K179T、H1G、H1W、H1R、H1K、H1S、H1L、K423L、K423H、K423P、K423T、K302R、H1N、N197A、V165M、D192A、D192E、V165A、V165G、V165L、M208A、A186M、H321V、Q98V、H324R、H324W、S323K、H324L、H324Q、H1*+H2E、H1*+H2V、Q280S、H1*+H2A、G304V、V410R、G304A、I430E、G149Q、Q169M、R181G、K461R、N311S、N311L、L351C、N215G、N311E、L351Q、N215G、N311D、D416L、A274W、H210S、H210S+P408Q、H210Y、P211T、P211T+V213T、H210S+V214T、P211T、V213T+V214S、K269Q+A274Y、K269Q+A274G、K269N+A274M、R172Q+N174Q、G50A+R172Q+L173F、R172Q+N174S、R172Q+L173F+N174Y、G50A+A51T+N174E、R172Q+N174T+A204T、N174S、R172Q+L173T+N174D、G50A+R172Q、R172K+L173I+N174S、R172Q+L173F+A204T、G50A+R172Q+N174T、R172Q+N174T、G50A+R172Q+N174D、N174D+A204V、G50A+R172N+N174S、G50A+R172N+N174T、G73V+R172Q+N174E、R172N+L173T+N174Q+S303R、G50S+R172K+N174D、N174T、G50A+A51T+K72H+R172Q+N174Q+A204V、A204V、R172Q、L173T+N174Q+A204V、R172K+L173F、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+A51T+R172Q+L173V、R172Q+L173I+N174S、L173V+N174S、G50A+R172D+N174D、G50A+R172D+N174Q、R172D+N174T、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、E345D+E346P+D476K+G477S、G304Q+D476G+G477K、E346P+D476K+G477S、E345D+D476K+G477S、E346T+D476K+G477A、E345D+E346P+D476G、K302Q+E346P+D476K+G477S、E346T+D476G+G477T、K302N+E345D+D476Q+G477Q、E345D+E346P+G477Q、L173F+N174Q、R172Q+L173F、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、R172D+L173F、R172D、A51V+R172Q+A204V、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172Q+A204V、L173I+N174D、W48L+A51T+R172Q+N174S+A204T、G50A+A51V+R172E+L173F+N174T+A204V、G50A+R172Q+L444P、R172Q+L173T+N174S、L173F+A204T、A51I+R172D、G50A+R172Q+N174S+A204T、R172Q+L173F+N174D、G50A+A51V+R172Q、R172Q+N174*、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、R172N+N174S、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、A51I+R172E+N174T、G50A+A51I+A204V、R172Q+N174D、G50A+R172E+L173V+N174T、A274E+G304Q+G305S+E345D+D476K+G477Q、E346P+D476Q+G477S、E345D+E346P+D476G+G477T、G304Q+E345D+E346T+D476G+G477S、E345D+E346T+D476G+G477A、E346P+D476Q、G304Q+E346T+D476K+G477Q、K302N+G304Q+E346P+D476K、G304A+E346K+G477K、G273V+G304S+E346P+D476G+G477T、K302Q+E345D+E346P+D476K+G477Q、E346P+G477S、G305S+E346P+D476Q+G477T、E345D+E346P+D476Q+G477A、E346T+D476K+G477S、E345D+D476Q+G477S、G304S+E346P+D476K+G477S、E346P+D476K+G477T、G304A+E345D+E346T+D476Q+G477Q、E346T+D476Q+G477A、R118L,R118S+G182A+T193K、R118P+G182A、R118P+G182S、R118S+E134D、E134D+K179L+G182N、R118S、R118S+G182A、R118S+N128L+G182S、E134D、G182S+A186V、R118D+K179L+G182A、R118P+G182N、K179L、R118D+G182N、R118S+E134D+G182S、E134D+A186E、R118S+N128Q+K179L、G182A+P432H、N128F+K179L、K179L+G182A、N128Q+A442V、K179L+A186S、N128Q+K179L+A186S、R118D、E346T+D476Q+G477K、E345D+D476G+G477S、K302Q+G304S+E345D+D476G+G477Q、E345D+E346P+G477S、R172E+L173T+N174T、G50A+R172D+L173T+N174S、G50A+N174D+A204T、R172Q+L173V、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、R172Q+L173F+N174D+A204T、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、A51T+L173F+N174Q+A204V、G50A+A51V+L173F+N174E+E471K、R172E+L173F+N174D、A51V+N174T+A204V、R172K+A204V、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、A51T+R172N+A204V、G50A+A51T+R172E+L173I、N174Q+A204V、G50A+A51V+L173F+N174*、R172E+N174D+A204T、A51T+R172N+L173*、R172N+L173F+N174Q+V489G,R172E+L173F、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、A51T+R172Q、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、A51I+N174D、G50A+N174E+A204T、R172Q+L173V+A204T、A51V+R172Q+L173F+N174S、A51T+R172D+N174Q、G50A+A51T+R172E+N174S、R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、A51V+L173V+A204V、E391L+K423P、T40K+V56T+R171E、G149Q+R171E、A113Y+G149Q+R171E+D192E+Q280S、H1L+A113Y+R171E+D192E、R171E+D192E+Q280S+Q361A+Y363L+E391L+K423P、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、R172Q+N174D+G304Q+E345D+E346T+D476G+G477S、K302Q+D476G+G477A、G304A+E346P+D476G+G477S、S255I+E345D+G477Q、E346T+G477A、G304A+E345D、K302Q+E346P+D476K+G477A、K302Q+E346P+G477A、G304S+E345D+D476K+G477Q、K302N+E345D+D476G、A113T+G304S+E345D+E346P+D476G+G477Q、R320S+S323M、G7E+R320M+S323M、D112H+R320A+S323N、K108E+G110D+A111T+D112H+R320S+S323M、R320A+S323N、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、Q98A+R320A+S323N、Q98T+R320A+H324L、G7E+Q98T+R320A、G7E+Q98A+R320M、G7N+R320S、R320A+S323N、G7L+P211Q+S303G+R320A、Q98A+A265S+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、Q98N+R320A+S323N、R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、R320A+H324L、G7S+R320A+S323N+H324Q、Q98S+R320A+S323N、G7K+R320M+H321Q、R320S+S323N、G7N+R320A+S323N、R320M+S323N、G7Q+R320S+H321N+S323M、R320A+H324Q、K302Q+E346P+D476K、K302Q+E346P+G477Q、K302Q+D476G+G477Q、E345D+E346P+D476Q+G477S、G304Q+E345D+E346T、E345D+E346T+D476G+G477S、D112N+R320M+S323M+E449G、V75I+R320A+S323N、G7X+Q98T+R320A、R320T、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、A87D+R320S+S323M、Q98K+K269N+R320A+S323M+H324Q、G7K+R320A+P408Q、G7K+R320A+H324L、Q98N+R320S+S323N、R320A+H321W+S323M+H324Q、R320S+S323M+H324Q、G7L+R320M+S323N、N28S+R320M+S323N、Q98S+R320A、G7E+R320A、T5*+G4*+N3*+R320A、G7E+R142I+R320A+E391K+A392P+R393*+Q394S、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323MR320V+D476Y、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、R320A+H321N+S323N、G7E+R320M、Q98A+R320A+S323M、G7Q+Q98T+R320A+S323M、R320M+S323M+H324Q、G7K+R320A、G7K+T246M+R320A+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、A51T+R172D+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+R172D+N174S、A51V+R172D、L173T+N174T+A204T、G50A+R172E+L173V+N174S、R172E+N174T、N28D+G109S+A119P+R172D+L173V+N174S、R172E+N174D、A51I+R172E+L173F、R172Q+A204V、G50A+A51T+R172E+N174T、R172N+N174T+A204V、R172K+N174S、R172D+N174S、R172D+L173V+N174D、G50A+A51T+R172Q+L173I、R172Q+N174E、G50A+R172E+L173T+N174S、G50A+A51T+R172E+A204V、R172D+N174D、L173V+N174D、R172D+L173F+N174D、G50A+R172E+N174T、L173F+N174Q+A204V、L173T+N174S+A204V+T255K、G50A+R172N+A204T、R172E+L173I+A204T、G50A+R172Q+L173V、A51T+R172D+N174D、R172K+L173V+N174S+A204T、R172E+L173T+N174S+A204T、G50A+A51V+R172D+N174T、R172D+L173I+N174S、L173T+N174T+A204V、R172N+N174D、G50A+L173I+L173I+N174T+N174T+N219K+W220F、G50A+R172E+L173F+N174Q、R172Q+N174T、G50A+R172N+N174E、R172N+N174T+H324N、G50A+R172Q+L173T+N174Q,R172K+L173V+N174S+A204T+L429F、G50A+R172E+L173F+N174T、R172D+L173V、R172E+L173T+N174S、R172D+L173I+N174S、A51V+R172Q+L173T、G50A+A51T+R172Q+L173V+A204V、G50A+A51T+R172D+L173F+N174T+K423P、N174E、T40I+A51L+R172D+L173F、G50A+R172E+L173F+N174Q+A204T、R172K+L173F+N174Q+A204V、R172N+L173I、G50A+R118D+W167F+R172D+N174Q、G50A+A51V+A113L+W167F+R172N+N174T+A204T、G50A+A51V+R118D+W167F+R172N+N174T+A204T、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+R118D+R172D+L173F、G50A+A51V+A113L+R118D+W167F+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+R118D+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R11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6Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+P146S+N174D+A204T、W140Y+W167F+R172K+A204V、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、Q98N+W167F+R320A+S323M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+W167F+R172N+A204V+G304Q+E345D+E346T、A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+A113L+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、G50A+A51V+A113L+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+R172N+N174T+A204T+R320A+S323N、G50A+A51V+N174S+R320A+S323N、G50A+R172D+N174D+R320V、G50A+A51T+R172E+A204T+E346T+D476K+G477A、L173T+A204T+K302Q+E346P+D476K+G477S、R172D+N174Q+E346T+D476K+G477A、L173T+A204T+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+E345D+D476K+G477S、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+A51T+N174S+A204T+S255I+E345D+G477Q、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+A51V+R172D+N174E+M208Y+V213S+V214T+L217M、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477AR172E+L173F+N174D+G304S+E345D+D476K+G477Q、R172E+L173F+N174D+E345D+E346P+D476G、R172E+L173F+N174D+R320A+S323N、R172E+L173F+N174D+E346T+A354V+G477A、R172E+L173F+N174D+E346T+G477A、R172E+L173F+N174D+R320V+D476Y、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、R172N+L173V+E345D+E346P+D476G、R172N+L173V+R320A+S323N、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、T5K+R172E+L173F+R320A+S323N、T5K+R172E+L173F+R320V+D476Y、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213T+V214T+L217M+R320A+H324Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)J洗滌劑中在15℃的溫度下測定時，所述變體具有至少1.3的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：W167F、K72S、K72R、T40K、T40M、Q361S、V291A、V56T、R171E、R171S、H1L+R171E+D192E、T40K+R171E、R171E+H324L+Q361A+Y363L、A113Y+R171E+Y363L+E391L+K423P、W140Y、R172S、A113Y、A113L、R172T、Y243G、Y243D、K269M、R118P、E391A、E391M、K179S、E391L、E391H、K179T、H1G、K423P、H324R、I430E、N215G、H210Y、P211T、H210S+V214T、G50A+R172Q、G73V+R172Q+N174E、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、R172Q、L173T+N174Q+A204V、G50A+A51T+R172Q+L173V、G50A+R172D+N174D、G50A+R172D+N174Q、R172D+N174T、G50A+A51V+R172N+N174T+A204T、E346P+D476K+G477S、E345D+E346P+G477Q、R172Q+L173F、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+A51V+R172D+L173F、R172D+L173F、R172D、G50A+R172K、G50A+A51V+R172D+L173F+N174Q+A204T、G50A+R172Q+L173I+N174T+A204T、G50A+A51V+R172E+L173F+N174T+A204V、R172Q+L173F+N174D、G50A+A51V+R172Q、R172Q+N174*、G50A+A51T+R172D、G50A+R172E+L173V+N174T、A274E+G304Q+G305S+E345D+D476K+G477Q、K302N+G304Q+E346P+D476K、K302Q+E345D+E346P+D476K+G477Q、E346T+D476Q+G477A、R118L、R118S+G182A+T193K、R118P+G182A、R118P+G182S、R118S+E134D、E134D+K179L+G182N、R118S+G182A、G182S+A186V、R118D+K179L+G182A、R118P+G182N、R118S+E134D+G182S、E134D+A186E、N128Q+K179L+A186S、R118D、R172Q+L173V、R172E+L173F+N174D、G50A+A51T+R172E+L173I、R172E+N174D+A204T、A51T+R172N+L173*、R172E+L173F、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172D+N174T、G50A+R172D、R172Q+L173V+A204T、A51T+R172D+N174Q、G50A+A51T+R172E+N174S、G149Q+R171E、A113Y+G149Q+R171E+D192E+Q280S、H1L+A113Y+R171E+D192E、R171E+D192E+Q280S+Q361A+Y363L+E391L+K423P、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、R172Q+N174D+G304Q+E345D+E346T+D476G+G477S、S255I+E345D+G477Q、E346T+G477A、G304S+E345D+D476K+G477Q、A113T+G304S+E345D+E346P+D476G+G477Q、G7Q+Q98S+R320S+H324Q、Q98A+R320A+S323N、G7N+R320S,R320A+S323N、G7L+P211Q+S303G+R320A、Q98A+A265S+R320A、R320M、G7P+R320S+S323K、G7Q+R320A+S323N、R320A+H324Q、G7X+Q98T+R320A、G7E+Q98A+K302R+R320A+S323N、G7K+R320A+P408Q、G7L+R320M+S323N、G7L+R320A+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、R320V+D476Y、G7H+Q98S+R320A+S323M+H324L,G7Q+R320S+H321N、R320A+H321N+S323N、Q98A+R320A+S323M、G7Q+Q98T+R320A+S323M、R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、A51T+R172D+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、R172Q+A204V、R172N+N174T+A204V、R172D+N174S、R172D+L173V+N174D、G50A+A51T+R172E+A204V、R172D+L173F+N174D、G50A+R172E+N174T、L173F+N174Q+A204V、G50A+R172N+A204T、R172E+L173I+A204T、A51T+R172D+N174D、R172K+L173V+N174S+A204T、R172E+L173T+N174S+A204T、G50A+A51V+R172D+N174T、R172D+L173I+N174S、L173T+N174T+A204V、R172N+N174D、G50A+A51T+R172Q+L173V+A204V、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+A113L+R172N+L173V、R118D+W167F+R172Q+N174D、W167F+R172Q+N174D、A204T+G304Q+E345D+E346T+D476G+G477S、R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、A113L+W167F+R172Q+Y363L、T40K+G50A+R172Q+I430E、T40K+K72R+W167F、W167F+R172Q+E346T+Y363L、K72R+A113L+W167F+R172Q+N215G+Y363L、G50A+R172D+L173F+E471K、G50A+A51T+R172D+S255I+E345D+G477Q、G50A+R172D+N174T+S255I+E345D+G477Q、R172K+A204V+S255I+E345D+G477Q、R172K+A204V+S255I+E345D+K423P+G477Q、G50A+A51T+W140Y+R172D、G50A+A51V+W140Y+R172E+L173F+N174T+A204V、G50A+W140Y+R172D+N174Q、G50A+W140Y+R172N+N174T、G50A+A51V+W140Y+P146S+L173F+N174D、A113L+R118D+W167F+S255I+E345D+G477Q、K72R+A113L+W167F+S255I+E345D+G477Q、Q98N+M208Y+V213T+V214T+L217M+R320A+S323M、R172E+N174D+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、R172E+N174D+A204T+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、A51T+R172N+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172N+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51V+R172N+N174T+A204T+R320A+H321N+S323N、G50A+R172N+N174T+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+A113L+R172E+N174S+G304Q+E345D+E346T+V474T、G50A+A51T+Q169M+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+G149A+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V+R320A+S323N、G50A+A51T+W167F+R172N+L173V+M208Y+V213S+V214T+L217M、G50A+A51T+W167F+R172N+L173V+M208Y+V213T+V214T+L217M、R172N+L173F+N174Q+G304Q+R320A+S323N+E345D+E346T+D476G+G477S、T40K+K72R+W167F+R320A+S323N、R172D+L173I+N174S、G50A+A51I+R172D+L173V、G50A+A51L+R172N+L173V+A204T、R172D+L173T+N174D+A204T、R172N+L173V、G50A+R172K+N174Q、T5K+R172E+L173F、R172D+L173T+N174D、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+D476K+G477A、G4S+Y16D+T40K+G50A+R172N+N174S+A204T、T40K+G50A+K72R+W167F+R172N+N174S+A204T、G4S+T40K+K72R+Q98N+W167F+R218K+N226T+R320A+S323M、T40K+K72R+Q98N+R320A+S323M、T40K+K72R+R118D+W167F、T40K+A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172N+N174S+A204T、K72R+W167F+E346T+D476K+G477A+Y482F、G50A+A51V+K72R+W167F+R172E+L173F+N174T+A204V、K72R+Q98N+W167F+R320A+S323M、T40K+K72R+Q98N+W167F+R320A+S323M、T40K+G50A+A51V+R172N+N174T+A204T、T40K+G50A+A51V+W167F+R172N+N174T+A204T、T40K+G50A+A51V+K72R+R172N+N174T+A204T、T40K+K72R+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、L173F+N174D+A354V、L173F+N174E+G477S、G50A+A51V+R172D+L173F+A204V+K302Q+D476G+G477S、G50A+A51V+L173Q+R172*+N174T+G305S+E346P+G477T、R172D+L173F+N174D+E345D+E346P+W469L、T40K+K72R+W167F+N174D+A204T、W140Y+W167F+N174D、G50A+W140Y+W167F+N174D+A204T、T40K+K72R+W167F+R172K+A204V、T40K+W167F+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、T40K+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、W140Y+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、A51T+W140Y+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172N+A204T、T40K+G50A+R172N+A204T、G50A+W140Y+R172N+A204T、G50A+W140Y+W167F+R172N+A204T、W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、W140Y+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、T40K+G50A+K72R+W167F+R172D+N174T+E345D+G477Q、G50A+W140Y+R172D+N174T+E345D+E346P+D476G、G50A+W140Y+W167F+R172D+L173F+N174T+G304Q+E345D+E346P+D476G、T40K+K72R+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、T40K+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、W140Y+W167F+R172D+N174T+A204V+S255I+E345D+E346P+G477Q、W167F+R172D+N174T+A204V+S255I+E345D+G477Q、W140Y+W167F+R172D+N174T+A204V+S255I+E345D+E346P+G477Q、T40K+K72R+Q98N+W167F+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+V474I、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+R415K、Q98N+W140Y+W167F+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D、G50A+A51V+W140Y+P146S+W167F+R172E+L173F+N174T+A204V+R320A+S323N、T40K+G50A+A51V+K72R+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51V+W140Y+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51T+R172N+L173V+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+K302Q+E346P+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、G50A+A51V+R172N+N174T+A204T+E345D+D476K+G477S、G50A+R172D+N174Q+E345D+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、R172N+N174Q+E345D+D406A+I411M+N446K、G50S+R172N+N174Q+E345D、G50A+N174D+A204T+E345D+D476K+G477S、G50A+N174D+A204T+S255I+E345D+G477Q、G50A+N174D+A204T+G304S+E345D+D476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172K+A204V+G304S+E345D+D476K+G477Q、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+S255I+E345D+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M+R320A+S323N、G50A+A51V+R172N+N174T+A204T+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+A51T+R172D+R320A+S323N、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+R320A+S323N、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320A+S323M+D476Y、G50A+R172D+N174Q+R320V+D476Y、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、T40K+K72R+W167Y、T40K+K72R+W167H、W140Y+W167F+A204V、R172K+M208Y+V213T+V214T+L217M、R172K+M208Y+V213S+V214T+L217M、W140Y+W167F+S255I+E345D+G477Q、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、G7K+T40K+W167F+R320M+H321Q、G7K+T40K+K72R+W167F+R320M+H321Q、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+K72R+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+L85F+R172N+L173V+Q319K+R320A+S323N、R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+S255I+E345D+G477Q、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51V+R172D+N174E+R320A+S323N、G50A+A51V+R172D+N174E+G315E+R320A+S323N、G50A+A51T+R172E+A204T+E345D+D476K+G477S、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E,T40K+G50A+A51V+W167F+R172D+N174E、T40K+W167F+L173T+A204T、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、T40K+G50A+R172D+N174D+E346T+D476K+G477A、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、R172E+L173F+N174D+E346T+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、T5K+R172E+L173F+K302Q+E346P、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+L173F+N174D+M208Y+V213S+V214T+L217M、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、G50A+R172N+N174T+E346T+D476K、R118P+W140Y，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)J洗滌劑中在15℃的溫度下測定時，所述變體具有至少1.5的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：Y363L、W167F、R171E、W140Y、R118P、E391A、E391L、E391H、K179T、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+A51V+R172D+L173F、R118S+G182A+T193K、R118P+G182A、R118P+G182S、N128Q+K179L+A186S、R118D、R171E+D192E+Q280S+Q361A+Y363L+E391L+K423P、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、G7L+P211Q+S303G+R320A、G7L+R320A+S323M、G7K+R320A+S323N+P364S、R320A+H321N+S323N、R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、A51T+R172D+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+L173V+A204V、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51T+W167F+R172N+L173V、W167F+R172Q+E346T+Y363L、G50A+A51T+W140Y+R172D、G50A+W140Y+R172N+N174T、R172E+N174D+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+R172D+N174D+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+R320A+H321N+S323N+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+G149A+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V+R320A+S323N、T40K+K72R+W167F+R320A+S323N、G50A+A51I+R172D+L173V、R172D+L173T+N174D+A204T、R172N+L173V、T40K+G50A+K72R+W167F+R172N+N174S+A204T、G4S+T40K+K72R+Q98N+W167F+R218K+N226T+R320A+S323M、T40K+K72R+Q98N+R320A+S323M、T40K+G50A+A51V+K72R+R172N+N174T+A204T、T40K+K72R+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+A204V+K302Q+D476G+G477S、T40K+K72R+W167F+R172K+A204V、W140Y+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、A51T+W140Y+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172N+A204T、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、T40K+G50A+K72R+W167F+R172D+N174T+E345D+G477Q、G50A+A51V+W140Y+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、R172D+N174T+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、T40K+K72R+W167F+E346T+G477A、L173T+A204T+E346T+G477A、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476YG50A+A51V+W167F+R172E+L173F+N174T+A204V+G304、+E345D+E346T+D476G+G477T、G7Q+T40K+K72R+W167F、W167F+Q169M+R172E+N174S、W140Y+W167F+A204V、G7K+W167F+R320M+H321Q、G7K+K72R+W167F+R320M+H321Q、R172D+N174Q+E346T+D476K+G477A、G50A+A51V+R172D+N174E+E346T+D476K+G477A、R172E+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+R172E+N174S+G184S、G50A+A51T+R118P+R172E+G184S+A204T、R118P+L173T+G184S+A204T、G50A+A51V+R118P+R172D+N174E+G184S、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、G50A+R118P+R172D+N174D+G184S+E346T+D476K+G477A、R172N+L173V+E345D+D476K+G477S、R172N+L173V+S255I+E345D+G477Q、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+R320A+S323N+Y482F、G50A+R172D+N174Q+E346T、G50A+R172D+N174Q+R320V、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+R118P+W167F+G184S+M208Y+V213S+V214T+L217M、G50A+R172D+N174D+E346T+D476K，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)J洗滌劑中在30℃的溫度下測定時，所述變體具有至少1.1的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：T40K、Q361S、Q361A、E345S、E276S、W268F、V291A、V56A、V56T、R171E、K302A、L429A、A354V、K347M、A113Y+R171E、T40K+K179S、R171E+E391L、H1L+R171E+D192E、T40K+R171E、E471N、W140Y、R320A、A113Q、R172Y、A113N、R142K、R172L、R172L、R172S、A113Y、A113L、R142T、R172T、R172V、R172A、N174L、I241F、N174Y、N174G、Y243E、Y243I、Y243S、Y243G、Y243D、V165G、Y243T、N299K、Y160Q、P211D、K269L、K269N、K269R、F155Y、K269I、K269V、K269M、R118G、R118P、K179P、K179R、E391A、E391M、E391L、E391H、K179T、H1G、H1R、H1K、H1S、H1L、L217M、K423L、K423H、K423P、K423T、L217F、K302R、N296Q、H1N、D192E、N281Q、V165A、V165G、A186V、N281L、N281V、A186T、H321L、H324R、H324L、G7L、N128H、G182N、T193G、H1*+H2E、H1*+H2V、Q280S、G304R、V410R、G304A、G305S、I430E、G149Q、G149A、D476G、Q169M、R171H、N311S、N215G、N311E、G182A+V213T+V214S、H210S、H210Y、P211T+V213T、G182N+V213S、H210S+V214T、K269Q+A274W、K269H+A274C、K269N+A274M、G50A+R172Q+L173F、R172Q+L173F+N174Y、N174S、G50A+R172Q、R172K+L173I+N174S、G50A+A51T+R172Q、G50A+R172Q+L173T、G50A+R172Q+L173V、G50A+R172Q+N174D、G50A+R172N+N174S、G50A+R172N+N174T、R172Q、L173T+N174Q+A204V、G50A+R172Q+L173T+N174D、G50A+A51V+R172N+N174T+A204T、K302Q+E346P+D476K+G477S、G304Q+E346P+D476G、G304A+E346P+D476K+G477A、E346T+D476G+G477T、K302N+E345D+D476Q+G477Q、E345D+E346P+G477Q、R172Q+L173F、G50A+N174S、N174D、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、R172D+L173F、A51V+R172Q+A204V、G50A+R172K、G50A+R172Q+N174S、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172N+A204T、L173I+N174D、W48L+A51T+R172Q+N174S+A204T、G50A+A51V+R172E+L173F+N174T+A204V、G50A+R172Q+L444P、L173F+A204T、R172Q+L173F+N174D、G50A+A51V+R172Q、R172Q+N174*、G50A+A51T+R172D、G50A+R172E+L173F、L173V+N174T、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、A51I+R172E+N174T、G50A+A51I+A204V、R172Q+N174D、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51T+L173F、A274E+G304Q+G305S+E345D+D476K+G477Q、E345D+D476Q+G477K、G304A+E345D+D476Q+G477A、G304Q+E345D+E346T+D476G+G477S、E346T、K302N+E345D+D476G+G477K、K302N+G304Q+E346P+D476K、G304Q+E345D+E346T+D476G+G477T、K302N+E346P+D476Q+G477K,E345D+D476Q、G304S+E345D+E346T+D476Q+G477A、E346P+D476K+G477T、G304A+E345D+E346T+D476Q+G477Q、G304S+E346P+D476K+G477K、K302Q+E346P+D476K+G477T、E346T+D476Q+G477A、G304A+E345D+E346P+D476K+G477Q、R118S+G182A+T193K、R118P+G182A、E134D+K179L+G182N、G4V+E134D+K179L、E134D+A186E、N128F+K179L、N128Q+A442V、N128Q+K179L+A186S、R118D、E345D+D476Q+G477A、G304Q+E346P+D476G+G477S、E346T+D476K+G477Q+V489G、E346T+D476Q+G477K、E345D+D476G+G477S、D476K+G477Q、K302Q+G304S+E345D+D476G+G477Q、E345D+D476Q+G477Q、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、A51V+R172Q+N174S+A204V、G50A+N174D+A204T、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、R172K+A204V、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、A51T+R172N+A204V、G50A+A51T+R172E+L173I、N174Q+A204V、G50A+A51V+L173F+N174*、R172E+N174D+A204T、A51T+R172N+L173*、R172N+L173F+N174Q+V489G、G50A+R172S+N174H、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、R172Q+L173V+A204T、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、A51V+L173V+A204V、A113Y+G149Q+R171E+D192E+Q280S、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、R172Q+N174D+G304Q+E345D+E346T+D476G+G477S、K302Q+G304A+E345D+E346T+D476Q+G477Q、G305A+E345D、K302Q+E345D+D476K+G477Q、S255I+E345D+G477Q、E346T+G477A、G304A+E345D、K302Q+E346P+D476K+G477A、G305S+E345D+D476K+G477Q、K302N+E345D+E346P+D476Q+G477S、G304A+E346T+D476K+G477T、G304S+E345D+D476K+G477Q、R320S+S323M、K108E+G110D+A111T+D112H+R320S+S323M、Q98S+R320S、R320A+S323N、G7K+R320M+H321Q、R320S+S323N、R320A+H324Q、G304A+E346P+D476Q+G477T、K302Q+G304Q+D476K+G477K、G305S+E346P+D476K+G477Q、G304Q+E345D+E346T、R320A+H321W+S323M+H324Q、R320S+S323M+H324Q、Q98S+R320A、T5*+G4*+N3*+R320A、G7L+R320A+S323M、G7K+R320A+S323N+P364S、R320V+D476Y、G7H+Q98S+R320A+S323M+H324L、R320A+H321N+S323N、G7Q+Q98T+R320A+S323M、R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+A51T+L173V+A204V、G50A+R172N+L173V、R172E+N174T、R172Q+A204V、G50A+A51T+R172E+N174T、R172Q+L173F+N174T、R172K+N174S、R172Q+N174E、G50A+A51T+R172E+A204V、L173F+N174Q+A204V、L173T+N174S+A204V+T255K、G50A+R172N+A204T、R172E+L173I+A204T、G50A+R172Q+L173V、A51T+R172D+N174D、R172N+N174D、G50A+A51V+R172Q+N174Q、G50A+R172Q+L173T+N174Q、R172K+L173V+N174S+A204T+L429F、R172K+L173T、G50A+A51T+R172Q+L173V+A204V、R172Q+L173T、R172K+L173F+N174Q+A204V、R158G+N174E、A51T+N174D+A204V、G50A+R118D+W167F+R172D+N174Q、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+A113L+R172N+L173V、W167F+R172Q+N174D、A204T+G304Q+E345D+E346T+D476G+G477S、R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、A113L+W167F+R172Q+N215G、G50A+A113L+W167F+R172Q、G50A+W167F+R172Q、G50A+A113L+W167F+R172Q、G50A+A51T+R172D+E345D+E346P+D476G、G50A+R172D+N174Q+E345D+E346P+D476G、R171E+D192E+E345D+E346P+D476G、G50A+R172D+N174D+E345D+E346P+D476G、G50A+R172D+N174T+E345D+E346P+D476G、G50A+R172N+N174T+E345D+E346P+D476G、G50A+A51V+R172N+N174T+A204T+S255I+E345D、R172K+A204V+S255I+E345D+G477Q、R172K+A204V+S255I+E345D+K423P+G477Q、G50A+A51T+W140Y+R172D、G50A+W140Y+R172D+N174Q、G50A+A51V+W140Y+R172N+N174T+A204T、G50A+W140Y+R172N+N174T、G50A+A51V+W140Y+P146S+L173F+N174D、A113L+S255I+E345D+G477Q+V489G、K72R+A113L+W167F+S255I+E345D+G477Q、W167F+S255I+E345D+G477Q、Q98N+M208Y+V213S+V214T+L217M+R320A+S323M、Q98N+M208Y+V213T+V214T+L217M+R320A+S323M、R172E+N174D+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+A87S+Q169M+R172N+L173T+N174D+G304Q+E345D+E346T+A427V+D476G+G477S、G50A+R172D+N174Q+R320A+H321N+S323N、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213T+V214T+L217M、G50A+A51T+W167F+R172N+L173V+M208Y+V213T+V214T+L217M、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、L173F、Y160L、V165G、G50A+R172Q+L173V、G50A+R172N+A204T、G50A+A51I+R172D+L173V、R172D+L173T+N174D+A204T、R172N+L173V、T5K+R172E+L173F、A47S+G50A+R172K+L173F+N174D、R172D+L173T+N174D,G50A+A51T+R172N+L173V+E345D+E346P+D476G、N174D+A204T+E346T+D476K+G477A、T40K+G50A+K72R+W167F+R172N+N174S+A204T、G4S+T40K+K72R+Q98N+W167F+R218K+N226T+R320A+S323M、T40K+K72R+Q98N+R320A+S323M、T40K+K72R+A113L+W167F、T40K+G50A+W167F+R172N+N174S+A204T、T40K+K72R+E345D+E346P+D476G、K72R+W167F+E346T+D476K+G477A+Y482F、T40K+K72R+Q98N+W167F+R320A+S323M、T40K+G50A+A51V+R172N+N174T+A204T、T40K+G50A+A51V+K72R+R172N+N174T+A204T、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+N174T+E346T+D476K+G477A、G50A+L173T+N174E+A204T+E345D+S424Q、L173F+N174D+A354V、L173F+N174E+G477S、G50A+A51V+R172D+L173F+A204V+K302Q+D476G+G477S、G50A+A51V+L173Q+R172*+N174T+G305S+E346P+G477T、W140Y+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172N+A204T、G50A+W140Y+R172N+A204T、W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、W140Y+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、T40K+G50A+K72R+W167F+R172D+N174T+E345D+G477Q、G50A+W140Y+R172D+N174T+E345D+E346P+D476G、G50A+W140Y+W167F+R172D+L173F+N174T+G304Q+E345D+E346P+D476G、T40K+K72R+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、T40K+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、W140Y+W167F+R172D+N174T+A204V+S255N+E345D+G477Q、W167F+R172D+N174T+A204V+S255I+E345D+G477Q、W140Y+W167F+R172D+N174T+A204V+S255I+E345D+E346P+G477Q、T40K+Q98N+W167F+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+T431P、T40K+K72R+Q98N+W167F+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+V474I、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+R415K、Q98N+W140Y+W167F+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D、G50A+A51V+W140Y+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51T+R172N+L173V+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+K302Q+E346P+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、G50A+A51V+R172N+N174T+A204T+K302Q+E346P+D476K+G477S、G50A+A51V+R172N+N174T+A204T+E345D+D476K+G477S、N174D+A204T+K302Q+E346P+D476K+G477S、G50A+R172D+N174Q+K302Q+E346P+D476K+G477S、G50A+R172D+N174Q+E345D+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、G50S+R172N+N174Q+E345D+E346P+D476G、R172N+N174Q+E345D+D406A+I411M+N446K、G50S+R172N+N174Q+E345D、G50A+N174D+A204T+E345D+D476K+G477S、G50A+N174D+A204T+S255I+E345D+G477Q、G50A+N174D+A204T+G304S+E345D+D476K+G477Q、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、R172K+A204V+E345D+D476K+G477S、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D476K+G477A、G50A+R172N+A204T+E346T+D432A+D476K+G477A、G50A+R172N+A204T+E345D+D476K+G477S、G50A+R172N+A204T+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E345D+E346P+D476G、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+D476K+G477S、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M,G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、N174D+A204V+M208Y+V213T+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、R172E+N174D+A204T+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+E346T+G477A、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y,G50A+R172Q+L173T+E346T+G477A、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、R172E+L173F+N174T+A204V+E345D+E346T+G477A、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E346T+G477A、T40K+K72R+W167F+E346T+G477A、T40K+K72R+W167F+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、L173T+A204T+E346T+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+A51V+R172D+N174E+R320S+S323N+D476Y、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G7Q+T40K+K72R+W167F、G7E+T40K+K72R+W167F、T40K+K72R+W167Y、A51T+K72R+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、T40K+A51T+W167F+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174D+R320V、R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174Q+A204V+E345D+D476K+G477S、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+A204V+E345D+E346P+D476G、G50A+A51T+L85F+R172E+A204T+E345D+E346P+D476G、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+E346T+D476K+G477A、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51T+R172E+A204T+E345D+D476K+G477S、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、T40K+G50A+A51V+W167F+N174S、T40K+G50A+A51V+K72R+W167F+R172E+N174S、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+W167F+L173T+A204T、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172D+N174Q+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+R172S+N174S+E346T+D476K+G477A、G50A+R172T+N174S+E346T、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174D+R320A+S323M+A442V+D476Y、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+G304S+E345D+D476K+G477Q、G50A+R172D+N174Q+E346T、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172N+L173F+N174Q+V213S+V214T+L217M+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A113T+R172D+N174Q+E346T+D476K、G50A+R172D+N174D+E346T+D476K、N174D+E345D+E346P+D476K、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、K72R+W167F+E346T+D476K、R118P+W140Y、G7K+T40K+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)J洗滌劑中在30℃的溫度下測定時，所述變體具有至少1.3的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：Y363L、Q361S、Q361A、E345S、E276S、V291A、V56A、V56T、R171E、T40K+R171E、G149Q+R171E+Q361A+Y363L+K423P、W140Y、R172Y、A113N、R142K、R172L、R172L、R172S、A113Y、A113L、R172T、R172V、Y243S、Y243G、Y243D、V165G、Y243T、K269V、K269M、E391M、E391L、H1K、H1S、H1L、L217M、K423T、L217F、N296Q、H1N、V165A、G304R、V410R、G305S、I430E、G149Q、N215G、N174S、G50A+R172Q、G50A+R172Q+L173T、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、R172D+L173F、G50A+R172K、G50A+R172Q+N174S、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E+L173F、L173V+N174T、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、A51I+R172E+N174T、G50A+A51I+A204V、R172Q+N174D、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51T+L173F、E345D+D476Q+G477K、G304Q+E345D+E346T+D476G+G477S、E346T、E345D+D476Q、G304A+E345D+E346T+D476Q+G477Q、R118S+G182A+T193K、E345D+D476G+G477S、G50A+N174E+A204T、G50A+A51T+R172E+N174S、K302Q+G304A+E345D+E346T+D476Q+G477Q、S255I+E345D+G477Q、G304S+E345D+D476K+G477Q、R320V+D476Y、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、R172K+L173F+N174Q+A204V、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+W167F、K72R+A113L+W167F+S255I+E345D+G477Q、Q98N+M208Y+V213T+V214T+L217M+R320A+S323M、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+A51V+K72R+R172N+N174T+A204T、G50A+A51V+L173Q+R172*+N174T+G305S+E346P+G477T、W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、G50A+W140Y+W167F+R172D+L173F+N174T+G304Q+E345D+E346P+D476G、T40K+K72R+W167F+R172K+A204V+M208Y+V213S+V214T+L217M+S255I+R320A+H324Q+E345D+G477Q、W167F+R172D+N174T+A204V+S255I+E345D+G477Q、T40K+Q98N+W167F+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+T431P、T40K+K72R+Q98N+W167F+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+V474I、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+R415K、Q98N+W140Y+W167F+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51T+R172N+L173V+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+K302Q+E346P+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、G50A+A51V+R172N+N174T+A204T+K302Q+E346P+D476K+G477S、G50A+A51V+R172N+N174T+A204T+E345D+D476K+G477S、G50S+R172N+N174Q+E345D、R172K+A204V+K302Q+E346P+D476K+G477S、R172K+A204V+E345D+D476K、G50A+R172N+A204T+E345D+D476K+G477S、T40K+K72R+W167F+S255I+E345D+G477Q、T40K+K72R+W167F+G304S+E345D+D476K+G477Q、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、L173T+A204T+R320V+D476Y、G50A+A51V+R172D+N174E+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+G304Q+E345D+E346T+D476G+G477T、G50A+A51T+R172N+L173V+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+K302Q+E346P+D476K+G477S、G50A+A51V+R172D+N174E+G304S+E345D+D476K+G477Q、G50A+A51V+R172D+N174E+E345D+E346P+D476G、G50A+A51T+R172E+A204T+E345D+D476K+G477S、G50A+R172D+N174D+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+N174S+M208Y+V213S+V214T+L217M、G50A+A51V+R172E+N174S+M208Y+V213S+V214T+L217M、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、T40K+G50A+A51V+K72R+W167F+R172D+N174E、T40K+G50A+K72R+W167F+L173T+A204V、G50A+R172S+N174S+E346T+D476K+G477A、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+E345D+D476K+G477S、R172E+L173F+N174D+S255I+E345D+G477Q、T5K+R172E+L173F+K302Q+E346P+D476K+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+Q169M+R172E+N174S+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、T40K+K72R+W167F+R172N+L173F+N174Q+G304Q+E345D+E346T+G465K+D476G、K72R+W167F+E346T+D476K，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個具體的實(shí)施例中，當(dāng)在標(biāo)準(zhǔn)J洗滌劑中在30℃的溫度下測定時，所述變體具有至少1.5的改進(jìn)因子(IF)。在一個優(yōu)選的實(shí)施例中，該變體包括a)對應(yīng)于R181+G182、R181+H183、R181+G184、G182+H183、G182+G184、H183+G184，優(yōu)選G182+H183的氨基酸的成對缺失，以及b)以下改變的組合中的一種：E345S、V56T、R171E、R172Y、A113N、R142K、R172L、R172L、A113Y、A113L、Y243G、E391M、H1K、H1L、I430E、G50A+R172E+L173F、L173V+N174T、G50A+R172Q+L173F+N174Q、R172E+L173F+N174Q、G50A+A51I+A204V、R172Q+N174D、G50A+R172E+L173V+N174T、G50A+A51T+L173F、E345D+D476Q+G477K、G304Q+E345D+E346T+D476G+G477S、E346T、R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、L173F、Y160L、V165G、G50A+A51I+R172D+L173V、R172D+L173T+N174D+A204T、R172N+L173V、T5K+R172E+L173F、R172D+L173T+N174D、G50A+A51T+R172N+L173V+E345D+E346P+D476G、N174D+A204T+E346T+D476K+G477A、T40K+G50A+K72R+W167F+R172N+N174S+A204T、G4S+T40K+K72R+Q98N+W167F+R218K+N226T+R320A+S323M、T40K+K72R+Q98N+R320A+S323M、T40K+K72R+A113L+W167F、T40K+G50A+W167F+R172N+N174S+A204T、T40K+K72R+E345D+E346P+D476G、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G+G477S、G50A+L173T+N174E+A204T+E345D+S424Q、L173F+N174D+A354V、G50A+A51V+R172D+L173F+A204V+K302Q+D476G+G477S、W140Y+R172E+N174D+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+W140Y+R172N+A204T、T40K+G50A+W167F+R172D+N174T+E345D+E346P+D476G、W167F+R172D+N174T+A204V+S255I+E345D+G477Q、T40K+K72R+Q98N+W167F+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M、Q98N+W140Y+R172K+A204V+M208Y+V213T+V214T+L217M+S255I+R320A+S323M+E345D+V474I、G50A+A51T+R172D+K302Q+E346P+D476K+G477S、G50A+A51T+R172D+E345D+D476K+G477S、G50A+A51T+R172N+L173V+E345D+D476K+G477S、G50A+A51V+A113L+R172E+L173F+N174T+A204V+E345D+L405V+T414K、N174D+A204T+K302Q+E346P+D476K+G477S、R172D+N174T+K302Q+E346P+D476K+G477S、R172N+N174Q+E345D+D406A+I411M+N446K、G50A+N174D+A204T+E345D+D476K+G477S、N174D+A204T+G304S+E345D+D476K+G477Q、R172K+A204V+G304S+E345D+D476K+G477Q、G50A+R172N+A204T+E346T+D432A+D476K+G477A、G50A+R172N+A204T+E345D+E346P+D476G、G50A+A51V+W167F+R172E+L173F+N174T+M208Y+V213S+V214T+L217M+E346T+D476K+G477A、G50A+A51V+R172N+N174T+A204T+M208Y+V213T+V214T+L217M、G50A+A51V+R172N+N174T+A204T+M208Y+V213S+V214T+L217M、R172E+N174D+A204T+M208Y+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、A51T+R172N+A204V+M208Y+V213S+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、G50A+R172N+A204T+M208Y+V213T+V214T+L217M、G50A+R172N+A204T+M208Y+V213S+V214T+L217M、G50A+A51V+W167F+R172E+L173F+N174T+A204V+M208Y+V213T+V214T+L217M、R172N+L173V+E346T+G477A、G50A+A51T+R172N+L173V+R320A+S323M+D476Y、G50A+R172Q+L173T+E346T+G477A、R172K+A204V+R320A+S323N、G50A+A51V+W167F+R172E+L173F+N174T+A204V+E346T+G477A、G50A+A51V+W167F+R172E+L173F+N174T+A204V+R320V+D476Y、G50A+A51V+R172E+N174S+E346T+G477A、G50A+A51T+R172E+A204T+R320V+N457T+D476Y、G50A+A51V+R172D+N174E+R320V+D476Y、G50A+R172D+N174Q+E346T+G477A、G50A+R172D+N174Q+R320V+D476Y、G50A+R172N+A204T+K302Q+E346P+D476K+G477S、G7K+T40K+K72R+W167F、G50A+A51V+R172N+N174T+A204T+G304Q+E345D+E346T+D476G+G477T、G50A+R172Q+L173T+G304Q+E345D+E346T+D476G+G477T、G50A+R172D+N174D+R320V、L173T+A204T+G304S+E345D+D476K+G477Q、G50A+R118P+R172D+N174Q+G184S+E346T+D476K+G477A、G50A+A51V+R118P+N174S+G184S、G50A+R118P+R172E+G184S+A204T、T40K+G50A+A51V+W167F+N174S、T40K+W167F+L173T+A204T、G50A+R172S+N174S+E346T+D476K+G477A、G50A+R118P+R172D+N174Q+E346T+D476K+G477A、G50A+R172D+N174Q+G304S+E345D+I464T+G465E+D476K+G477Q、G50A+R172D+N174Q+E346T、R172E+L173F+N174D+K302Q+E346P+D476K+G477S、G57R+R172E+L173F+N174D+K302Q+E346P、R172E+L173F+N174D+E346T+D476K+G477A、R172E+L173F+N174D+T246M+S255I+E345D+G477Q、G50A+A51T+K72R+W167F+Q169M+R172E+N174S+G304Q+E345D+E346T、R172E+L173F+N174D+V213T+V214T+L217M、G50A+R118P+R172D+N174T+E345D+E346P+D476G、R118P+R172E+N174D+G184S+A204T+G304Q+E345D+E346T+E391L+D476G+G477S、G50A+A51T+R118P+R172E+N174S+G184S+V213T+V214T+L217M+G304Q+E345D+E346T+D476G+G477S、N174D+E345D+E346P+D476K、T40K+K72R+R172N+L173F+N174Q+G304Q+E345D+E346T+D476G、G50A+R172N+N174T+E346T+D476K、R118P+W140Y、G7K+T40K+W167F+R320A+S323N+P364S，當(dāng)使用SEQIDNO:1進(jìn)行編號時。在一個實(shí)施例中，該親本α-淀粉酶具有SEQIDNO:1、SEQIDNO:2、SEQIDNO:4、SEQIDNO:7、SEQIDNO:8、SEQIDNO:9、SEQIDNO:10、SEQIDNO:11、SEQIDNO:12、SEQIDNO:13、SEQIDNO:14、SEQIDNO:15、或SEQIDNO:16中所示的氨基酸序列。在一個實(shí)施例中，本發(fā)明的α-淀粉酶變體是分離的變體。在一個優(yōu)選的實(shí)施例中，a)包括對應(yīng)于H183+G184的氨基酸的成對缺失。在另一個實(shí)施例中，a)包括對應(yīng)于R181+G182的氨基酸的成對缺失。在另一個實(shí)施例中，a)包括對應(yīng)于R181+H183的氨基酸的成對缺失。在另一個實(shí)施例中，a)包括對應(yīng)于R181+G184的氨基酸的成對缺失。在另一個實(shí)施例中，a)包括對應(yīng)于G182+H183的氨基酸的成對缺失。在另一個實(shí)施例中，a)包括對應(yīng)于G182+G184的氨基酸的成對缺失。在另一個實(shí)施例中，a)進(jìn)一步包括在R181、G182、H183和G184的非缺失的位置中的一個或兩個處的取代。在一個實(shí)施例中，本發(fā)明的變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在一個實(shí)施例中，本發(fā)明的變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:4的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:7的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:8的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:9的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:10的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:11的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:12的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:13的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:14的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:15的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少90％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少91％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少92％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少93％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少94％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少96％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少97％序列一致性但小于100％序列一致性。在又另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少98％序列一致性但小于100％序列一致性。在另一個實(shí)施例中，該變體與具有SEQIDNO:16的氨基酸序列的多肽具有至少99％序列一致性但小于100％序列一致性。與親本α-淀粉酶(例如，SEQIDNO:2的α-淀粉酶)相比或與相對于如本發(fā)明的變體的a)而言具有相應(yīng)改變的SEQIDNO:1的α-淀粉酶相比，由此獲得的變體具有改進(jìn)的洗滌性能。即，本發(fā)明的變體的洗滌性能可優(yōu)選地與相對于a)的改變具有與變體相同的改變的親本α-淀粉酶進(jìn)行比較。因此，如果本發(fā)明的變體是SEQIDNO:1的α-淀粉酶的變體，所述變體包含a)181*+182*的缺失，和b)本發(fā)明的取代中的一個或多個，則該洗滌性能優(yōu)選地可以與具有181*+182*氨基酸缺失的SEQIDNO:1進(jìn)行比較并得以改進(jìn)。這些變體還具有以下優(yōu)點(diǎn)，即它們在低溫下具有超過本領(lǐng)域已知的α-淀粉酶(如SP707α-淀粉酶(本文的SEQIDNO:4)，其比本發(fā)明的變體相對于a)具有對應(yīng)的改變)的改進(jìn)的洗滌性能。如果在實(shí)例1的一種或多種條件下改進(jìn)洗滌性能，即如果改進(jìn)因子(IF)在以下任一種中高于1.0，則洗滌性能被認(rèn)為是改進(jìn)的：a)在15℃下的標(biāo)準(zhǔn)洗滌劑A中，其中該α-淀粉酶變體濃度為0.2mg/L洗滌溶液，b)在40℃下的標(biāo)準(zhǔn)洗滌劑A中，其中該α-淀粉酶變體濃度為0.05mg/L洗滌溶液，c)在15℃下的標(biāo)準(zhǔn)洗滌劑J中，其中該α-淀粉酶變體濃度為0.2mg/L洗滌溶液，或在d)在30℃下的標(biāo)準(zhǔn)洗滌劑J中，其中該α-淀粉酶變體濃度為0.05mg/L洗滌溶液。實(shí)例1中描述了這些洗滌條件。優(yōu)選地，該改進(jìn)因子(IF)是1.05以上。在另一個實(shí)施例中，該變體是親本α-淀粉酶的變體，該變體由以下多核苷酸編碼，該多核苷酸在中嚴(yán)格條件、中-高格條件、高嚴(yán)格條件或非常高嚴(yán)格條件下與(i)SEQIDNO:3的成熟多肽編碼序列、或(ii)(i)的全長互補(bǔ)體雜交。在一個優(yōu)選實(shí)施例中，本發(fā)明涉及以下多核苷酸，該多核苷酸在高嚴(yán)格條件下與(i)SEQIDNO:3的成熟多肽編碼序列，或(ii)(i)的全長互補(bǔ)體雜交。在另一個優(yōu)選實(shí)施例中，本發(fā)明涉及以下多核苷酸，該多核苷酸在非常高嚴(yán)格條件下與(i)SEQIDNO:3的成熟多肽編碼序列，或(ii)(i)的全長互補(bǔ)體雜交。SEQIDNO:3的多核苷酸或其子序列，連同SEQIDNO:1和2的多肽或其片段可根據(jù)本領(lǐng)域熟知的方法用于設(shè)計(jì)核酸探針以鑒定和克隆來自不同屬或種的株系的、編碼具有α-淀粉酶活性的多肽的DNA。具體地，可以遵循標(biāo)準(zhǔn)DNA印跡程序，使用此類探針與感興趣的細(xì)胞的基因組DNA或cDNA雜交，以便鑒定和分離其中的對應(yīng)基因。這類探針可以明顯短于完整序列，但是長度應(yīng)為至少15，例如至少25、至少35、或至少70個核苷酸。優(yōu)選地，核酸探針的長度為至少100個核苷酸，例如長度為至少200個核苷酸、至少300個核苷酸、至少400個核苷酸、至少500個核苷酸、至少600個核苷酸、至少700個核苷酸、至少800個核苷酸、或至少900個核苷酸。DNA和RNA探針二者均可使用。通常將探針標(biāo)記以探測相應(yīng)的基因(例如，用32P、3H、35S、生物素或抗生物素蛋白標(biāo)記)。這類探針涵蓋于本發(fā)明中?？梢葬槍εc以上描述的探針雜交并且編碼出具有α-淀粉酶活性的多肽的DNA對從這類其他菌株制備的基因組DNA或cDNA庫進(jìn)行篩選?？梢酝ㄟ^瓊脂糖或聚丙烯酰胺凝膠電泳，或通過其它分離技術(shù)分離來自這些其它菌株的基因組或其它DNA。來自文庫的DNA或分離的DNA可轉(zhuǎn)移到并固定在硝酸纖維素或其他適合的載體材料上。為了鑒定與SEQIDNO:3或其子序列雜交的克隆或DNA，將載體材料用于DNA印跡中。出于本發(fā)明的目的，雜交表明多核苷酸在非常低到非常高嚴(yán)格條件下與一種被標(biāo)記的核酸探針雜交，該探針對應(yīng)于(i)SEQIDNO:3；(ii)SEQIDNO:3的成熟多肽編碼序列；(iii)其全長互補(bǔ)體；或(iv)其子序列?？梢允褂美鏧-射線膠片或本領(lǐng)域已知的任何其他檢測手段來檢測在這些條件下核酸探針雜交的分子。在另一個實(shí)施例中，本發(fā)明涉及具有α-淀粉酶活性的α-淀粉酶變體，該α-淀粉酶變體由以下多核苷酸編碼，該多核苷酸與SEQIDNO:3的成熟多肽編碼序列具有至少70％如至少80％，或至少90％如至少95％、至少96％、至少97％、至少98％、至少99％、或100％的序列一致性。在另外的實(shí)施例中，本發(fā)明涉及α-淀粉酶變體，該α-淀粉酶變體具有α-淀粉酶活性并且與SEQIDNO:1具有至少95％序列一致性，該多肽由以下多核苷酸編碼，該多核苷酸與SEQIDNO:3的成熟多肽編碼序列具有至少70％如至少80％、或至少85％或至少90％的序列一致性。本發(fā)明還提供了改進(jìn)具有SEQIDNO:1的氨基酸序列或與其具有至少90％序列一致性的親本α-淀粉酶的洗滌性能的方法，所述方法包括以下步驟：a)在對應(yīng)于SEQIDNO:1的成熟多肽位置R181、G182、H183和G184的親本α-淀粉酶中的位置，取代和/或缺失兩個或更多個氨基酸，以及b)將在以下位置：1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483中的一個或多個處的取代，和/或?qū)?yīng)于SEQIDNO:1的成熟多肽的1、2、3、4、5、172、173、或174的一個或多個位置處的缺失引入親本α-淀粉酶，其中該所得的變體與SEQIDNO:1的成熟多肽具有至少95％如至少97％但小于100％序列一致性，并且其中該所得的變體具有α-淀粉酶活性和與親本α-淀粉酶相比的改進(jìn)的洗滌性能。在一個實(shí)施例中，步驟a)包括缺失在位置R181、G182、H183和G184處的所述氨基酸中的兩個，如這些氨基酸對應(yīng)于SEQIDNO:1的R181+G182、R181+H183、R181+G184、G182+H183、G182+G184或H183+G184。在一個優(yōu)選的實(shí)施例中，缺失在位置183+184處的氨基酸。在一個實(shí)施例中，b)包括選自下組的取代或缺失或由它們組成，該組由以下各項(xiàng)組成：H1*、H1L、H1G、H1W、H1R、H1K、H1S、H1L、H1N、H1V、H2*、H2E、H2V、H2A、H2C、H2Q、N3*、N3C、N3D、N3S、N3C、G4*、G4V、G4S、T5*、T5K、G7S、G7L、G7E、G7Q、G7D、G7N、G7K、G7A、G7P、G7H、M9V、Y16D、N25D、R26Q、N28D、N28S、S36D、T40K、T40M、T40I、A47G、A47S、W48L、G50A、G50S、A51T、A51V、A51I、A51L、A51Q、A51P、A51S、A51F、V56A、V56T、G67E、K72S、K72R、K72H、G73V、V75I、V75F、L85F、Q86H、A87S、A87D、Q98V、Q98S、Q98A、Q98N、Q98T、Q98L、Q98K、G109S、D112H、D112N、A113Y、A113H、A113Q、A113S、A113N、A113L、A113T、R118K、R118G、R118P、R118L、R118S、R118D、A119P、N128G、N128V、N128L、N128T、N128H、N128M、N128F、N128Q、G133Q、G133V、E134D、T136N、W140Y、T141S、R142Q、R142K、R142T、R142S、D144Q、D144T、P146S、G149Q、G149R、G149K、G149A、G149L、F155Y、R158G、R158A、Y160H、Y160L、Y160R、Y160Q、Y160G、V165G、V165M、V165A、V165L、V165Q、V165S、W167L、W167F、W167Y、W167H、Q169K、Q169R、Q169G、Q169M、R171E、R171S、R171H、R172*、R172Y、R172L、R172S、R172P、R172T、R172V、R172A、R172M、R172Q、R172K、R172N、R172D、R172E、L173V、L173T、L173F、L173I、N174L、N174Y、N174G、N174Q、N174S、N174E、N174T、N174D、N174H、K179S、K179M、K179P、K179R、K179A、K179T、K179L、R181G、G182N、G182A、G182S、G182N、G182V、G184S、G184N、G184*、A186E、A186V、A186S、A186T、A186M、A186W、A186H、D192E、D192A、D192G、T193V、T193M、T193S、T193G、T193A、T193N、E194S、E194A、N195F、N197A、M200L、M202A、A204T、A204V、A204G、I206Y、M208S、M208G、M208W、M208Y、H210M、H210Y、H210S、H210D、P211E、P211G、P211V、P211D、P211A、P211W、P211T、P211H、P211Q、E212D、V213T、V213S、V214I、V214S、V214T、N215A、N215G、N215D、L217M、L217F、R218K、N219S、N219K、N219E、N219T、N219G、N219R、W220F、N226T、I241F、Y243E、Y243L、Y243I、Y243F、Y243S、Y243G、Y243D、Y243T、Y243P、T246M、S255I、S255N、S255K、A265S、W268F、W268L、K269G、K269S、K269L、K269R、K269N、K269I、K269V、K269M、K269Q、K269H、N270A、N270P、N270G、N270Y、G273V、A274K、A274W、A274T、A274S、A274E、A274C、A274Y、A274L、A274M、A274H、A274R、A274V、A274I、E276S、E276N、Q280R、Q280S、Q280K、Q280H、T282G、N283H、N283L、N283D、N283V、N283A、N283R、N283G、V291A、H294G、Y295N、N296Q、N299K、N299G、N299T、K302A、K302R、K302Q、K302N、S303R、S303G、G304R、G304V、G304A、G304S、G304Q、G305S、G305A、G305N、G305R、G305T、N311S、N311L、N311E、N311D、G315E、Q319K、R320K、R320A、R320S、R320M、R320T、R320V、H321V、H321A、H321L、H321Q、H321N、H321W、H321K、S323K、S323E、S323W、S323M、S323N、S323R、S323Q、H324R、H324W、H324L、H324Q、H324A、H324N、D330A、D330S、D330S、D330A、*336aG、*336bH、*336cG、*336dG、E336G、F343W、E345A、E345S、E345D、E346G、E346A、E346P、E346T、E346K、K349M、K349A、L351A、L351C、L351H、L351Q、L351S、L351K、A354V、L355V、Q361S、Q361A、Y363L、P364S、T376K、P380Q、R383K、E391A、E391T、E391M、E391L、E391K、E391H、E391N、H402N、L405V、D406A、P408H、P408Q、V410R、I411M、T414K、R415K、E416K、D418L、D418N、D418E、D418H、K423N、K423W、K423L、K423H、K423P、K423T、S424Q、A427V、L429A、L429F、I430M、I430L、I430E、T431P、K438N、R439G、A442V、N446K、A447V、A447T、E449K、E449G、K463R、N457T、K463R、I464T、I464S、G465L,S466F、D467G、W469L、E471N、E471K、H473S、V474T、V474I、D476G、D476K、D476Q、D476Y、G477A、G477S、G477Q、G477K、G477T、S478A、Y482F、K483R、H1*+H2E、H1*+H2V、H1*+H2A、H1*+N3C、H1L+A113Y+R171E+D192E、H1*+H2*+G7S、H1L+R171E+D192E、H2C、T5*+G4*+N3*+R320A、G4V+E134D+K179L、G7E+R320M+S323M、G7Q+Q98S+R320S+H324Q、G7E+R320A+H324Q、G7L+Q98N+R320A+S323N、G7E+Q98T+R320A、G7L+R320S+S323M、G7D+Q98A+R320M、G7N+Q98L+R320A+S323M、G7E+Q98A+R320M、G7N+R320S、G7K+R320A+S323M+H324L、G7L+P211Q+S303G+R320A、G7N+R320A+S323M、G7Q+R320S+S323M、G7N+R320A、G7E+R320A+S323M、G7A+Q98L+R320M、G7A+R320M、G7P+R320S+S323K、G7Q+R320A+S323N、G7L+Q98A+R320A+S323M、G7Q+R320M+S323N+H324W、G7S+R320A+S323N+H324Q、G7L+R320A、G7K+R320M+H321Q、G7N+R320A+S323N、G7Q+R320S+H321N+S323M、G7Q+R320A+S323M、G7L+R320S+S323M、G7N+Q98S+R320M+S323N、G7Q+R320A+S323R、G7E+Q98A+K302R+R320A+S323N、G7A+R320S+H321W+S323M、G7K+R320A+P408Q、G7K+R320A+H324L、G7L+R320M+S323N、G7L+R320A+S323M、G7E+R320A+P320Q+S323M、G7K+R320A+S323N+P364S、G7Q+R320A+H321Q+S323M、G7N+R320M、G7H+Q98S+R320A+S323M+H324L、G7Q+R320S+H321N、G7E+R320M、G7Q+Q98T+R320A+S323M、G7K+R320A、G7K+T246M+R320A+S323M、G7N+M9V+Q98A+R320S+S323M、G7Q+Q98A+R320M+S323M、G7Q+Q86H+R320A+S323M、N28D+G109S+A119P+R172D+L173V+N174S、N28S+R320M+S323N、T40I+A51L+R172D+L173F、T40K+G50A+R172Q+I430E、T40K+E346T、T40K+K72R+W167F、T40K+K72R+W167F+R320A+S323N、T40K+K72R+W140Y+W167F、G50A+R172Q+L173F、G50A+A51T+N174E、G50A+A51T+N174E、G50A+L173F、G50A+A51T+R172Q+N174Q+E471K、G50A+R172Q、G50A+A51V+R172N+N174S、G50A+A51T+R172Q、G50A+L173F+N174Q、G50A+R172Q+N174T、G50A+R172Q+L173T、G50A+R172Q+N174D、G50A+L173F+N174T、G50A+R172N+N174S、G50A+R172N+N174T、G50S+R172K+N174D、G50A+A51T+K72H+R172Q+N174Q+A204V、G50A+L173V+N174S、G50A+R172Q+L173T+N174D、G50A+N174E、G50A+L173T、G50A+A51T+R172Q+L173V、G50A+N174T+A204V、G50A+R172D+N174D、G50A+R172D+N174Q、G50A+L173V+A204T、G50A+A51V+R172N+N174T+A204T、G50A+N174S、G50A+R172Q+L173V+N174S、G50A+R172Q+A204T、G50A+R172Q+N174Q、G50A+A51V+R172D+L173F、G50A+A51I+R172D+N174*、G50A+R172K、G50A+R172Q+N174S、G50A+A51V+R172D+L173F+N174Q+A204T、G50S+R172N+N174Q、G50A+R172Q+L173I+N174T+A204T、G50A+R172E、G50A+R172Q+A204V、G50A+A51V+R172E+L173F+N174T+A204V、G50A+L173V、G50A+R172Q+L444P、G50A+A51T+R172N+L173V、G50A+R172Q+N174S+A204T、G50A+A51V+R172Q、G50A+A51T+R172D、G50A+A51T+R172N+N174D+G182V、G50A+R172E+L173F、G50A+A51T+R172Q+N174E、G50A+R172Q+L173F+N174Q、G50A+A51I+A204V、G50A+L173F+N174S、G50A+R172E+L173V+N174T、G50A+A51L+N174S+A447V、G50A+A51T+L173F、G50A+R172Q+L173I、G50A+A51V+L173F+N174D、G50A+R172D+L173T、G50A+A51T+R172Q+L173F+N174Q、G50A+R172Q+N174Q+A204T、G50A+R172D+L173T+N174S、G50A+N174D+A204T、G50A+A51T+R172N+L173I+N174Q、G50A+L173T+N174S+A204V、G50A+A51T+R172Q+A204V、G50A+L173F+N174Q+A204V、G50A+A51V+L173F+N174E+E471K、G50A+A51V+R172Q+A204V、G50A+A51Q+R172Q、G50A+A51T+R172E+L173I、G50A+A51V+L173F+N174*、G50A+R172S+N174H、G50A+A51T+A87S+R172N+L173T+N174D、G50A+R172N+L173T+N174D、G50A+R172E+L173F+N174D、G50A+R172D+N174T、G50A+A51T+R172Q+N174T、G50A+R172D、G50A+N174E+A204T、G50A+A51T+L173F+N174S、G50A+A51T+R172E+N174S、G50A+A51T+R172Q+N174Q、G50A+A51T+R172Q+L173F+N174T、G50A+R172Q+N174T+G304Q+E345D+E346T+D476G+G477S、G50A+R172D+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172D+L173F+N174Q+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+R172Q+L173I+N174T+A204T+G304Q+E345D+E346T+D476G+G477S、G50A+A51Q+R172Q+G304Q+E345D+E346T+D476G+G477S、G50A+A51V+R172Q+A204V+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+A87S+R172N+L173T+N174D+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172E+N174S+G304Q+E345D+E346T+D476G+G477S、G50A+A51T+R172Q+N174S+A204V、G50A+A51T+L173V+A204V、G50A+R172D+N174S、G50A+R172N、G50A+R172N+L173V、G50A+R172E+L173V+N174S、G50A+A51T+R172E+N174T、G50A+A51T+R172Q+L173I、G50A+R172E+L173T+N174S、G50A+A51T+R172E+A204V、G50A+R172E+N174T、G50A+R172N+A204T、G50A+R172Q+L173V、G50A+A51T+R172E、G50A+A51V+R172D+N174T、G50A+L173I+L173I+N174T+N174T+N219K+W220F、G50A+R172E+L173F+N174Q+A762、G50A+A51V+R172Q+N174Q、G50A+R172N+N174E、G50A+R172Q+L173T+N174Q、G50A+R172E+L173F+N174T、G50A+A51T+R172Q+L173V+A204V、G50A+A51T+R172D+L173F+N174T+K423P、G50A+R172E+L173F+N174Q+A204T、G50A+A113L+R172D+N174Q、G50A+R118D+W167F+R172D+N174Q、G50A+A51S+A113L+R118D+R172D+N174Q、G50A+R118D+R172D+N174Q、G50A+A51V+A113L+W167F+R172N+N174T+A204T、G50A+A51V+R118D+W167F+R172N+N174T+A204T、G50A+A51V+W167F+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R172N+N174T+A204T、G50A+A51V+R118D+R172N+N174T+A204T、G50A+A51V+A113L+R118D+R172D+L173F、G50A+A51V+R118D+R172D+L173F、G50A+A51V+A113L+R118D+W167F+R172D+L173F、G50A+A113L+W167F+R172Q+L173I+N174T+A204T、G50A+W167F+R172Q+L173I+N174T+A204T、G50A+R118D+W167F+R172Q+L173I+N174T+A204T、G50A+A113L+R118D+R172Q+L173I+N174T+A204T、G50A+A113L+R172Q+L173I+N174T+A204T、G50A+R118D+R172Q+L173I+N174T+A204T、G50A+A51V+R118D+W167F+R172E+L173F+N174T+A204V、G50A+A51V+W167F+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R172E+L173F+N174T+A204V、G50A+A51V+A113L+R118D+R172E+L173F+N174T+A204V、G50A+A51V+R118D+R172E+L173F+N174T+A204V、G50A+A51T+A113L+W167F+R172N+L173V、G50A+A51T+W167F+R172N+L173V、G50A+A51T+R118D+W167F+R172N+L173V、G50A+A51T+A113L+R118D+R172N+L173V、G50A+A51T+A113L+R172N+L173V、G50A+A51T+R118D+R172N+L173V、G50A+A113L+W167F+R172Q+A10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4T+E346T+D476K、K72R+W167F+E346T、K72R+W167F+E346T+D476K、R118P+W140Y、G50A+A51V+R118P+R172N+N174T+G184S+A204T、R172N+N174T+G184S+A204T、R118P+E346T+G477A、G7K+T40K+W167F+R320A+S323N+P364S、或G7K+T40K+K72R+W167F+R320A+S323N+P364S，當(dāng)SEQIDNO:1用于編號時。在一個優(yōu)選的實(shí)施例中，該變體相對于該親本α-淀粉酶具有改進(jìn)的特性，其中該改進(jìn)的特性選自下組，該組由以下各項(xiàng)組成：催化效率、催化速率、化學(xué)穩(wěn)定性、氧化穩(wěn)定性、pH活性、pH穩(wěn)定性、比活性、存儲條件下穩(wěn)定性、底物結(jié)合、底物切割、底物特異性、底物穩(wěn)定性、表面特性、熱活性、熱穩(wěn)定性，優(yōu)選地低溫下的改進(jìn)的洗滌性能、洗滌劑穩(wěn)定性和螯合劑穩(wěn)定性。在另一個實(shí)施例中，該變體相對于SEQIDNO:2的α-淀粉酶在液體洗滌劑中具有相等的或改進(jìn)的穩(wěn)定性。在另一個實(shí)施例中，該變體相對于SEQIDNO:1的α-淀粉酶在液體洗滌劑中具有相等的或改進(jìn)的穩(wěn)定性，該變體比本發(fā)明的變體相對于a)具有對應(yīng)的改變。即，本發(fā)明的變體的洗滌劑穩(wěn)定性可優(yōu)選與SEQIDNO:1的α-淀粉酶相比，其與對應(yīng)于SEQIDNO:1的α-淀粉酶的181、182、183和184的位置的相對于改變的變體具有相同的改變。在一個實(shí)施例中，引入SEQIDNO:1的多肽中的氨基酸取代和/或缺失的數(shù)目高達(dá)30，例如1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、或30個。在一個實(shí)施例中，引入SEQIDNO:1的多肽中的氨基酸取代和/或缺失的數(shù)目多達(dá)10個，例如1、2、3、4、5、6、7、8、9或10個。氨基酸改變可以具有次要性質(zhì)，即不顯著影響蛋白質(zhì)的折疊和/或活性的保守氨基酸取代或插入；典型地1-30個氨基酸的小缺失；小的氨基-或羧基末端延伸，如氨基末端蛋氨酸殘基；至多20-25個殘基的小接頭肽；或通過改變凈電荷或另一功能來促進(jìn)純化的小延伸，如多組氨酸序列、抗原性表位或結(jié)合結(jié)構(gòu)域。保守取代的實(shí)例在下組之內(nèi)：堿性氨基酸(精氨酸、賴氨酸和組氨酸)、酸性氨基酸(谷氨酸和天冬氨酸)、極性氨基酸(谷氨酰胺和天冬酰胺)、疏水氨基酸(亮氨酸、異亮氨酸和纈氨酸)、芳族氨基酸(苯丙氨酸、色氨酸和酪氨酸)、以及小氨基酸(甘氨酸、丙氨酸、絲氨酸、蘇氨酸以及甲硫氨酸)。一般不會改變比活性的氨基酸取代是本領(lǐng)域已知的并且例如由H.諾伊拉特(Neurath)和R.L.希爾(Hill)，1979，在蛋白質(zhì)(TheProteins)，學(xué)術(shù)出版社(AcademicPress)，紐約中描述。常見取代是Ala/Ser、Val/Ile、Asp/Glu、Thr/Ser、Ala/Gly、Ala/Thr、Ser/Asn、Ala/Val、Ser/Gly、Tyr/Phe、Ala/Pro、Lys/Arg、Asp/Asn、Leu/Ile、Leu/Val、Ala/Glu、以及Asp/Gly?？梢愿鶕?jù)本領(lǐng)域中已知的程序，如定點(diǎn)誘變或丙氨酸掃描誘變(坎寧漢(Cunningham)和威爾斯(Wells)，1989，科學(xué)(Science)244:1081-1085)來鑒定多肽中的必需氨基酸。在后一種技術(shù)中，在分子中的每個殘基處引入單丙氨酸突變，并測試所得的突變分子的α-淀粉酶活性以鑒定對分子活性關(guān)鍵的氨基酸殘基。還參見希爾頓(Hilton)等人,1996,生物化學(xué)雜志(J.Biol.Chem.)271:4699-4708。酶活性位點(diǎn)或其他生物學(xué)相互作用也可以通過對結(jié)構(gòu)進(jìn)行物理學(xué)分析來進(jìn)行確定，如通過以下技術(shù)例如核磁共振、結(jié)晶學(xué)、電子衍射、或光親和標(biāo)記，與假定接觸位點(diǎn)氨基酸的突變相結(jié)合來進(jìn)行確定。參見，例如，德沃斯(deVos)等人，1992，科學(xué)(Science)255:306-312；史密斯(Smith)等人，1992，分子生物學(xué)雜志(J.Mol.Biol.)224:899-904；Wlodaver等人，1992，歐洲生化學(xué)會聯(lián)合會快報(FEBSLett.)309:59-64。還可以從與相關(guān)多肽的比對推斷鑒別必需氨基酸。SEQIDNO:2的氨基酸序列中的必需氨基酸位于為催化殘基的位置D236、E266和D333處。此外，該Y58、H107、R234、H240、H332對于形成該活性位點(diǎn)而言是關(guān)鍵的。因此，氨基酸D236、E266、D333、Y58、H107、R234、H240、H332優(yōu)選不應(yīng)被突變。可以做出單個或多個氨基酸取代、缺失和/或插入并且使用誘變、重組和/或改組的已知方法進(jìn)行測試，隨后進(jìn)行相關(guān)篩選程序，如由里德哈爾-奧爾森(Reidhaar-Olson)和薩奧爾(Sauer)，1988，科學(xué)(Science)241:53-57；博維(Bowie)和薩奧爾，1989，美國國家科學(xué)院院刊(Proc.Natl.Acad.Sci.USA)86:2152-2156；WO95/17413；或WO95/22625披露的那些?？梢允褂玫钠渌椒òㄒ族ePCR、噬菌體展示(例如，羅曼(Lowman)等人，1991，生物化學(xué)(Biochemistry)30:10832-10837；美國專利號5,223,409；WO92/06204)和區(qū)域定向誘變(德比舍爾(Derbyshire)等人，1986，基因(Gene)46:145；Ner等人，1988，DNA7:127)。誘變/改組方法可以與高通量、自動化的篩選方法組合以檢測由宿主細(xì)胞表達(dá)的克隆的、誘變的多肽的活性(內(nèi)斯(Ness)等人，1999，自然生物技術(shù)(NatureBiotechnology)17:893-896)。編碼活性多肽的誘變的DNA分子可以回收自宿主細(xì)胞，并且使用本領(lǐng)域的標(biāo)準(zhǔn)方法對其進(jìn)行迅速測序。這些方法允許迅速確定多肽中單個氨基酸殘基的重要性。親本α-淀粉酶在一個優(yōu)選的實(shí)施例中，該變體是一種親本α-淀粉酶的變體，該親本α-淀粉酶選自下組，該組由以下各項(xiàng)組成：a.與SEQIDNO:1的成熟多肽具有至少90％序列一致性的多肽；b.與SEQIDNO:4的成熟多肽具有至少90％序列一致性的多肽；c.SEQIDNO:1的成熟多肽的片段，該片段具有α-淀粉酶活性；d.SEQIDNO:4的成熟多肽的片段，該片段具有α-淀粉酶活性；e.與針對SEQIDNO:1或4的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽；在其他實(shí)施例中，該親本α-淀粉酶與SEQIDNO:1具有至少91％，或至少92％、或至少93％、或至少94％、或至少95％、或至少96％，例如至少97％、至少98％、或至少99％的序列一致性。在其他實(shí)施例中，該親本α-淀粉酶與SEQIDNO:4具有至少91％，或至少92％、或至少93％、或至少94％、或至少95％、或至少96％，例如至少97％、至少98％、或至少99％的序列一致性。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:2的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:2的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:2的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:7的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:7的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:7的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:8的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:8的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:8的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:9的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:9的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:9的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:10的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:10的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:10的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:11的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:11的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:11的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:12的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:12的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:12的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:13的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:13的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:13的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:14的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:14的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:14的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:15的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:15的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:15的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在另一方面，該親本α-淀粉酶可以是(a)一種與SEQIDNO:16的成熟多肽具有至少90％序列一致性的多肽；(b)SEQIDNO:16的成熟多肽的一個片段，該片段具有α-淀粉酶活性或(c)一種與針對SEQIDNO:16的成熟多肽產(chǎn)生的抗體具有免疫交叉反應(yīng)性的多肽。在一個實(shí)施例中，該親本α-淀粉酶包括使用SEQIDNO:1進(jìn)行編號的N195F+I206Y取代。即，該親本α-淀粉酶可以是具有使用SEQIDNO:1進(jìn)行編號的N195F+I206Y的取代的SEQIDNO:4、7、8、9、10、11、12、13、14、15或16中的任何一個。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:1的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:2的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:4的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:7的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:8的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:9的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:10的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:11的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:12的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:13的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:14的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:15的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在一方面，該親本α-淀粉酶的氨基酸序列與SEQIDNO:16的成熟多肽相差不多于10個氨基酸，例如1、2、3、4、5、6、7、8或9個氨基酸。在另一方面，該親本α-淀粉酶包含SEQIDNO:1的氨基酸序列或由其組成。在另一方面，該親本α-淀粉酶包含SEQIDNO:2的氨基酸序列或由其組成。在又另一個實(shí)施例中，該親本α-淀粉酶是SEQIDNO:1的成熟多肽的一個等位基因變體。該親本α-淀粉酶可以是融合多肽或可切割融合多肽，其中另一種多肽在本發(fā)明多肽的N-末端或C-末端處融合。通過將編碼另一多肽的多核苷酸融合到本發(fā)明的多核苷酸而產(chǎn)生融合多肽。用于產(chǎn)生融合多肽的技術(shù)在本領(lǐng)域是已知的，并且包括連接編碼多肽的編碼序列，這樣使得它們在框內(nèi)并且使得融合多肽的表達(dá)處于相同的一個或多個啟動子和終止子的控制下。還可以使用內(nèi)含肽技術(shù)構(gòu)建融合多肽，其中在翻譯后產(chǎn)生融合多肽(庫珀(Cooper)等人，1993，歐洲分子生物學(xué)學(xué)會雜志12:2575-2583；道森(Dawson)，1994，科學(xué)(Science)266:776-779)。融合多肽可以在兩種多肽之間進(jìn)一步包括切割位點(diǎn)。在融合蛋白分泌之時，該位點(diǎn)被切割，從而釋放出這兩種多肽。切割位點(diǎn)的實(shí)例包括但不限于以下各項(xiàng)中披露的位點(diǎn)：馬丁(Martin)等人，2003，工業(yè)微生物學(xué)與生物技術(shù)雜志(J.Ind.Microbiol.Biotechnol.)3:568-576；斯韋蒂納(Svetina)等人，2000，生物技術(shù)雜志(J.Biotechnol.)76:245-251；拉斯馬森(Rasmussen)-威爾遜(Wilson)等人，1997，應(yīng)用環(huán)境微生物學(xué)(Appl.Environ.Microbiol.)63:3488-3493；華德(Ward)等人，1995，生物技術(shù)(Biotechnology)13:498-503；以及孔特拉斯(Contreras)等人，1991，生物技術(shù)9:378-381；伊頓(Eaton)等人，1986，生物化學(xué)(Biochemistry)25:505-512；柯林斯(Collins)-萊斯(Racie)等人，1995，生物技術(shù)13:982-987；卡特(Carter)等人，1989，蛋白：結(jié)構(gòu)、功能和遺傳學(xué)(Proteins：Structure，F(xiàn)unction，andGenetics)6:240-248；以及史蒂文斯(Stevens)，2003，世界藥物發(fā)現(xiàn)(DrugDiscoveryWorld)4:35-48。該親本α-淀粉酶可以從任何屬類的微生物中獲得。出于本發(fā)明的目的，如在此結(jié)合一種給定的來源使用的術(shù)語“從……中獲得”應(yīng)意指由多核苷酸編碼的親本是由該來源或由其中已經(jīng)插入來自該來源的多核苷酸的菌株產(chǎn)生的。在一方面，該親本是胞外分泌的。該親本α-淀粉酶可以是細(xì)菌α-淀粉酶。例如，該親本α-淀粉酶可以是一種革蘭氏陽性細(xì)菌多肽，如芽孢桿菌屬α-淀粉酶。還可以通過本領(lǐng)域已知的方法人工制造SEQIDNO1和2的α-淀粉酶連同其變體。變體的制備本發(fā)明還涉及用于獲得具有α-淀粉酶活性的變體的方法，這些方法包括將以下各項(xiàng)引入與SEQIDNO:1具有至少95％序列一致性的親本α-淀粉酶中：a)在親本α-淀粉酶所述的對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的位置中的兩個或多個位置處的取代和/或缺失，以及b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的成熟多肽的1、2、3、4、5、172、173、或174的一個或多個位置處的缺失，其中該所得的變體與SEQIDNO:1的成熟多肽具有至少95％如至少97％但小于100％序列一致性，其中該變體具有α-淀粉酶活性；并且回收所述變體。a)和b)的缺失和/或取代可以如以上所描述。可以使用本領(lǐng)域已知的任何誘變程序來制備這些變體，如定點(diǎn)誘變、合成基因構(gòu)建、半合成基因構(gòu)建、隨機(jī)誘變、改組等。同樣地，SEQIDNO:1、2、4、5、6、7、8、9、10、11、12、13、14、15和16的多肽可以通過本領(lǐng)域技術(shù)人員已知的方式通過合成基因構(gòu)建來產(chǎn)生。定點(diǎn)誘變是在編碼該親本的多核苷酸中的一個或多個限定位點(diǎn)處引入一個或多個(例如，若干個)突變的技術(shù)。通過使用涉及含有所希望的突變的寡核苷酸引物的PCR可以體外實(shí)現(xiàn)定點(diǎn)誘變。也可以通過盒式誘變進(jìn)行體外定點(diǎn)誘變，所述盒式誘變涉及由限制酶在包括編碼親本的多核苷酸的質(zhì)粒中的位點(diǎn)處切割并且隨后將含有突變的寡核苷酸連接在多核苷酸中。通常，消化該質(zhì)粒與該寡核苷酸的限制酶是相同的，以允許該質(zhì)粒的粘性末端以及插入片段彼此連接。參見，例如，謝勒(Scherer)和戴維斯(Davis)，1979，美國國家科學(xué)院院刊(Proc.Natl.Acad.Sci.USA)76:4949-4955；以及巴頓(Barton)等人，1990，核酸研究(NucleicAcidsRes.)18:7349-4966。還可以通過本領(lǐng)域已知的方法體內(nèi)實(shí)現(xiàn)定點(diǎn)誘變。參見例如，美國專利申請公開號2004/0171154；斯道瑞希(Storici)等人，2001，自然生物技術(shù)(NatureBiotechnol.)19:773-776；卡倫(Kren)等人，1998，自然醫(yī)學(xué)(Nat.Med.)4:285-290；以及凱利薩諾(Calissano)和馬奇諾(Macino)，1996，真菌遺傳學(xué)簡訊(FungalGenet.Newslett.)43:15-16。任何定點(diǎn)誘變方法可用于本發(fā)明。存在可用于制備變體的很多可商購的試劑盒。合成基因構(gòu)建需要體外合成設(shè)計(jì)的多核苷酸分子以編碼感興趣的多肽。基因合成可以利用多種技術(shù)來進(jìn)行，如由田(Tian)等人(2004，自然(Nature)432:1050-1054)所述的基于多路微芯片的技術(shù)、以及其中在光可編程的微流芯片上合成并組裝寡核苷酸的類似技術(shù)。可以做出單個或多個氨基酸取代、缺失和/或插入并且使用誘變、重組和/或改組的已知方法進(jìn)行測試，隨后進(jìn)行相關(guān)篩選程序，如由里德哈爾-奧爾森(Reidhaar-Olson)和薩奧爾(Sauer)，1988，科學(xué)(Science)241:53-57；博維(Bowie)和薩奧爾，1989，美國國家科學(xué)院院刊(Proc.Natl.Acad.Sci.USA)86:2152-2156；WO95/17413；或WO95/22625披露的那些?？梢允褂玫钠渌椒òㄒ族ePCR、噬菌體展示(例如，羅曼(Lowman)等人，1991，生物化學(xué)(Biochemistry)30:10832-10837；美國專利號5,223,409；WO92/06204)和區(qū)域定向誘變(德比舍爾(Derbyshire)等人，1986，基因(Gene)46:145；Ner等人，1988，DNA7:127)。誘變/改組方法可以與高通量、自動化的篩選方法組合以檢測由宿主細(xì)胞表達(dá)的克隆的、誘變的多肽的活性(內(nèi)斯(Ness)等人，1999，自然生物技術(shù)(NatureBiotechnology)17:893-896)。能夠從宿主細(xì)胞回收編碼活性多肽的誘變的DNA分子，并且使用本領(lǐng)域內(nèi)標(biāo)準(zhǔn)方法快速測序。這些方法允許迅速確定多肽中單個氨基酸殘基的重要性。通過組合合成基因構(gòu)建、和/或定點(diǎn)誘變、和/或隨機(jī)誘變、和/或改組的多個方面來實(shí)現(xiàn)半合成基因構(gòu)建。半合成構(gòu)建典型地是，利用合成的多核苷酸片段的過程結(jié)合PCR技術(shù)。因此，基因的限定的區(qū)域可以從頭合成，而其他區(qū)域可以使用位點(diǎn)特異性誘變引物來擴(kuò)增，而還有其他區(qū)域可以經(jīng)受易錯PCR或非易錯PCR擴(kuò)增。然后可以對多核苷酸子序列進(jìn)行改組。多核苷酸本發(fā)明還涉及編碼本發(fā)明的變體的多核苷酸。因此，在一方面，本發(fā)明涉及編碼一種變體的多核苷酸，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性。在一個實(shí)施例中，這些多核苷酸是分離的多核苷酸。核酸構(gòu)建體本發(fā)明還涉及核酸構(gòu)建體，這些核酸構(gòu)建體包含可操作地連接至一個或多個控制序列的本發(fā)明的多核苷酸，在與控制序列相容的條件下，這些控制序列指導(dǎo)編碼序列在適合的宿主細(xì)胞中表達(dá)。因此，在一方面，本發(fā)明涉及一種包含編碼一種變體的多核苷酸的核酸構(gòu)建體，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性，其中該多核苷酸可操作地連接至一個或多個控制序列，所述控制序列在與所述控制序列相容的條件下指導(dǎo)所述編碼序列在合適的宿主細(xì)胞中的表達(dá)?？梢杂迷S多方式操作所述多核苷酸以便于多肽的表達(dá)。取決于表達(dá)載體，在其插入載體以前操縱多核苷酸可以是希望的或必需的。用于利用重組DNA方法修飾多核苷酸的技術(shù)是本領(lǐng)域熟知的。該控制序列可以是啟動子，即，被宿主細(xì)胞識別以對編碼本發(fā)明的多肽的多核苷酸進(jìn)行表達(dá)的多核苷酸。該啟動子包含轉(zhuǎn)錄控制序列，這些序列介導(dǎo)該多肽的表達(dá)。該啟動子可以是在宿主細(xì)胞中顯示出轉(zhuǎn)錄活性的任何多核苷酸，包括變體、截短型及雜合型啟動子，并且可以由編碼與該宿主細(xì)胞同源或異源的細(xì)胞外或細(xì)胞內(nèi)多肽的基因獲得。用于在細(xì)菌宿主細(xì)胞中指導(dǎo)本發(fā)明的核酸構(gòu)建體的轉(zhuǎn)錄的適合啟動子的實(shí)例是從以下基因中獲得的啟動子：解淀粉芽孢桿菌α-淀粉酶基因(amyQ)、地衣芽孢桿菌α-淀粉酶基因(amyL)、地衣芽孢桿菌青霉素酶基因(penP)、嗜熱脂肪芽孢桿菌麥芽糖淀粉酶基因(amyM)、枯草芽孢桿菌果聚糖蔗糖酶基因(sacB)、枯草芽孢桿菌xylA和xylB基因、蘇云金芽孢桿菌cryIIIA基因(阿蓋塞(Agaisse)和勒爾克呂(Lereclus)，1994，分子微生物學(xué)(MolecularMicrobiology)13:97-107)、大腸桿菌lac操縱子、大腸桿菌trc啟動子(埃貢(Egon)等人，1988，基因(Gene)69:301-315)、天藍(lán)鏈霉菌瓊脂水解酶基因(dagA)、以及原核β-內(nèi)酰胺酶基因(維拉-卡馬洛夫(Villa-Kamaroff)等人，1978，美國國家科學(xué)院院刊(Proc.Natl.Acad.Sci.USA)75:3727-3731)以及tac啟動子(德波爾(DeBoer)等人，1983，美國國家科學(xué)院院刊80:21-25)。其他啟動子描述在吉爾伯特(Gilbert)等人，1980，科學(xué)美國人(ScientificAmerican)242:74-94的“來自重組細(xì)菌的有用蛋白質(zhì)(Usefulproteinsfromrecombinantbacteria)”；以及在薩姆布魯克(Sambrook)等人，1989，同上。串聯(lián)啟動子的實(shí)例披露在WO99/43835中?？刂菩蛄羞€可以是由宿主細(xì)胞識別以終止轉(zhuǎn)錄的轉(zhuǎn)錄終止子。該終止子可操作地連接到編碼該多肽的多核苷酸的3’-末端。在該宿主細(xì)胞中起作用的任何終止子都可以用于本發(fā)明中。用于細(xì)菌宿主細(xì)胞的優(yōu)選終止子是從克勞氏芽孢桿菌堿性蛋白酶(aprH)、地衣芽孢桿菌α-淀粉酶(amyL)以及大腸桿菌核糖體RNA(rrnB)的基因獲得?？刂菩蛄羞€可以是啟動子下游和基因的編碼序列上游的mRNA穩(wěn)定子區(qū)，它增加該基因的表達(dá)。適合的mRNA穩(wěn)定子區(qū)的實(shí)例是從以下獲得的：蘇云金芽孢桿菌cryIIIA基因(WO94/25612)和枯草芽孢桿菌SP82基因(化(Hue)等人，1995，細(xì)菌學(xué)雜志(JournalofBacteriology)177:3465-3471)。該控制序列還可以是前導(dǎo)子，一種對宿主細(xì)胞翻譯很重要的非翻譯mRNA區(qū)域。該前導(dǎo)子可操作地連接到編碼該多肽的多核苷酸的5’-末端?？梢允褂迷谒拗骷?xì)胞中起作用的任何前導(dǎo)子?？刂菩蛄羞€可以是聚腺苷酸化序列，一種可操作地連接至該多核苷酸的3’-末端并且當(dāng)轉(zhuǎn)錄時由宿主細(xì)胞識別為將聚腺苷酸殘基添加至所轉(zhuǎn)錄的mRNA的信號的序列?？梢允褂迷谒拗骷?xì)胞中起作用的任何聚腺苷酸化序列。對于酵母宿主細(xì)胞有用的聚腺苷酸化序列在郭(Guo)和謝爾曼(Sherman)，1995，分子細(xì)胞生物學(xué)(Mol.CellularBiol.)15:5983-5990中得以描述?？刂菩蛄幸部梢允蔷幋a與多肽的N-末端連接并指導(dǎo)多肽進(jìn)入細(xì)胞的分泌通路的信號肽的信號肽編碼區(qū)。多核苷酸的編碼序列的5’-端可以固有地包含在翻譯閱讀框中與編碼多肽的編碼序列的區(qū)段天然地連接的信號肽編碼序列?？商娲兀幋a序列的5’-端可以包含對于該編碼序列而言是外源的信號肽編碼序列。外源信號肽編碼序列在編碼序列不天然地包含信號肽編碼序列時可為必需的?？商娲?，外源信號肽編碼序列可以簡單地替代天然信號肽編碼序列，以便增強(qiáng)多肽的分泌。然而，可以使用指導(dǎo)所表達(dá)多肽進(jìn)入宿主細(xì)胞的分泌通路的任何信號肽編碼序列。用于細(xì)菌宿主細(xì)胞的有效信號肽編碼序列是從以下各項(xiàng)的基因獲得的信號肽編碼序列：芽孢桿菌屬NCIB11837產(chǎn)麥芽糖淀粉酶、地衣芽孢桿菌枯草桿菌蛋白酶、地衣芽孢桿菌β-內(nèi)酰胺酶、嗜熱脂肪芽孢桿菌α-淀粉酶、嗜熱脂肪芽孢桿菌中性蛋白酶(nprT、nprS、nprM)以及枯草芽孢桿菌prsA。西蒙納(Simonen)和帕爾瓦(Palva)，1993，微生物學(xué)評論(MicrobiologicalReviews)57:109-137描述了另外的信號肽。該控制序列還可以是編碼位于多肽的N-末端處的前肽的前肽編碼序列。生成的多肽被稱為前體酶(proenzyme)或多肽原(或在一些情況下被稱為酶原(zymogen))。多肽原通常是無活性的并且可以通過催化切割或自身催化切割來自多肽原的前肽而轉(zhuǎn)化為活性多肽。前肽編碼序列可以從以下各項(xiàng)的基因獲得：枯草芽孢桿菌堿性蛋白酶(aprE)、枯草芽孢桿菌中性蛋白酶(nprT)、嗜熱毀絲霉漆酶(WO95/33836)、米黑根毛霉天冬氨酸蛋白酶、以及釀酒酵母α-因子。在信號肽序列和前肽序列二者都存在的情況下，該前肽序列定位成緊鄰多肽的N-末端并且該信號肽序列定位成緊鄰該前肽序列的N-末端。還可能希望地是添加調(diào)節(jié)序列，這些調(diào)節(jié)序列相對于宿主細(xì)胞的生長來調(diào)節(jié)多肽的表達(dá)。調(diào)節(jié)序列的實(shí)例是使得基因的表達(dá)響應(yīng)于化學(xué)或物理刺激(包括調(diào)節(jié)化合物的存在)而開啟或關(guān)閉的那些。原核系統(tǒng)中的調(diào)節(jié)序列包括lac、tac以及trp操縱子系統(tǒng)。在酵母中，可以使用ADH2系統(tǒng)或GAL1系統(tǒng)。在絲狀真菌中，可以使用黑曲霉葡糖淀粉酶啟動子、米曲霉TAKAα-淀粉酶啟動子和米曲霉葡糖淀粉酶啟動子、里氏木霉纖維二糖水解酶I啟動子以及里氏木霉纖維二糖水解酶II啟動子。調(diào)控序列的其他實(shí)例是允許基因擴(kuò)增的那些。在真核系統(tǒng)中，這些調(diào)控序列包括在甲氨蝶呤存在下被擴(kuò)增的二氫葉酸還原酶基因以及用重金屬擴(kuò)增的金屬硫蛋白基因。在這些情況中，編碼多肽的多核苷酸將與調(diào)控序列可操作地連接。表達(dá)載體本發(fā)明還涉及包含本發(fā)明的多核苷酸、啟動子、以及轉(zhuǎn)錄和翻譯終止信號的重組表達(dá)載體。因此，本發(fā)明涉及一種包含編碼一種變體的多核苷酸的重組表達(dá)載體，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性，該表達(dá)載體進(jìn)一步包含啟動子、以及轉(zhuǎn)錄和翻譯終止信號。不同的核苷酸和控制序列可以連接在一起以產(chǎn)生重組表達(dá)載體，該重組表達(dá)載體可以包括一個或多個便利的限制酶切位點(diǎn)以允許在這些位點(diǎn)處插入或取代編碼該多肽的多核苷酸?？商娲?，該多核苷酸可以通過將該多核苷酸或包括該多核苷酸的核酸構(gòu)建體插入用于表達(dá)的適當(dāng)載體中來表達(dá)。在產(chǎn)生該表達(dá)載體時，該編碼序列位于該載體中，這樣使得該編碼序列與該供表達(dá)的適當(dāng)控制序列可操作地連接。重組表達(dá)載體可以是任何載體(例如，質(zhì)粒或病毒)，其能夠方便地進(jìn)行重組DNA程序，并且能夠引起多核苷酸的表達(dá)。載體的選擇將典型地取決于該載體與有待引入該載體的宿主細(xì)胞的相容性。該載體可以是線性的或閉合的環(huán)狀質(zhì)粒。該載體可以是自主復(fù)制載體，即，作為染色體外實(shí)體存在的載體，其復(fù)制獨(dú)立于染色體復(fù)制，例如，質(zhì)粒、染色體外元件、微染色體或人工染色體。該載體可包含任何用以保證自我復(fù)制的要素。可替代地，該載體可以是這樣載體，當(dāng)它被引入該宿主細(xì)胞中時，被整合到基因組中并且與其中已整合了它的一個或多個染色體一起復(fù)制。此外，可以使用單一載體或質(zhì)?；騼蓚€或更多個載體或質(zhì)粒(這些載體或質(zhì)粒共同含有待引入到宿主細(xì)胞的基因組中的總DNA)或轉(zhuǎn)座子。該載體優(yōu)選包含一個或多個允許方便地選擇轉(zhuǎn)化細(xì)胞、轉(zhuǎn)染細(xì)胞、轉(zhuǎn)導(dǎo)細(xì)胞等細(xì)胞的選擇性標(biāo)記。選擇性標(biāo)記是基因，其產(chǎn)物提供殺生物劑或病毒抗性、對重金屬的抗性、對營養(yǎng)缺陷型的原養(yǎng)性(prototrophytoauxotrophs)等。細(xì)菌性選擇性標(biāo)記的實(shí)例是地衣芽孢桿菌或枯草芽孢桿菌dal基因，或賦予抗生素抗性(如氨比西林、氯霉素、卡那霉素、新霉素、大觀霉素或四環(huán)素抗性)的標(biāo)記。用于酵母宿主細(xì)胞的適合的標(biāo)記包括但不限于ADE2、HIS3、LEU2、LYS2、MET3、TRP1、以及URA3。用于在絲狀真菌宿主細(xì)胞中使用的選擇性標(biāo)記包括但不限于，adeA(磷酸核糖酰氨基咪唑-琥珀羧胺合酶)、adeB(磷酸核糖酰-氨基咪唑合酶)、amdS(乙酰胺酶)、argB(鳥氨酸氨甲?；D(zhuǎn)移酶)、bar(草丁膦乙酰轉(zhuǎn)移酶)、hph(潮霉素磷酸轉(zhuǎn)移酶)、niaD(硝酸還原酶)、pyrG(乳清酸核苷-5'-磷酸脫羧酶)、sC(硫酸腺苷基轉(zhuǎn)移酶)、以及trpC(鄰氨基苯甲酸合酶)、連同其等效物。優(yōu)選在曲霉屬細(xì)胞中使用的是構(gòu)巢曲霉或米曲霉amdS和pyrG基因以及吸水鏈霉菌bar基因。優(yōu)選在木霉屬細(xì)胞中使用的是adeA、adeB、amdS、hph以及pyrG基因。選擇性標(biāo)記可以是如在WO2010/039889中描述的雙選擇性標(biāo)記系統(tǒng)。在一方面中，雙選擇性標(biāo)記是hph-tk雙選擇性標(biāo)記系統(tǒng)。該載體優(yōu)選包含允許載體整合到宿主細(xì)胞的基因組中或載體在細(xì)胞中獨(dú)立于基因組自主復(fù)制的一個或多個元件。對于整合到該宿主細(xì)胞基因組中，該載體可以依靠編碼該多肽的多核苷酸序列或者用于通過同源或非同源重組整合到該基因組中的該載體的任何其他元件。可替代地，該載體可以包含額外的多核苷酸，用于指導(dǎo)通過同源重組整合入宿主細(xì)胞基因組染色體中的精確位置。為了增加在精確位置整合的可能性，這些整合的元件應(yīng)包含足夠數(shù)量的核酸，例如100至10,000個堿基對、400至10,000個堿基對、以及800至10,000個堿基對，這些堿基對與對應(yīng)的靶序列具有高度的序列一致性以提高同源重組的可能性。這些整合元件可以是與宿主細(xì)胞的基因組內(nèi)的靶序列同源的任何序列。此外，這些整合元件可以是非編碼多核苷酸或編碼多核苷酸。另一個方面，該載體可以通過非同源重組整合到宿主細(xì)胞的基因組中。對于自主復(fù)制，該載體可以進(jìn)一步包括使該載體能夠在所討論的宿主細(xì)胞中自主復(fù)制的復(fù)制起點(diǎn)。復(fù)制起點(diǎn)可以是在細(xì)胞中起作用的介導(dǎo)自主復(fù)制的任何質(zhì)粒復(fù)制子。術(shù)語“復(fù)制起點(diǎn)(originofreplication)”或“質(zhì)粒復(fù)制子(plasmidreplicator)”意指使得質(zhì)粒或載體可在體內(nèi)復(fù)制的多核苷酸。細(xì)菌復(fù)制起點(diǎn)的實(shí)例是允許在大腸桿菌中復(fù)制的質(zhì)粒pBR322、pUC19、pACYC177、以及pACYC184的復(fù)制起點(diǎn)，以及允許在芽孢桿菌屬中復(fù)制的質(zhì)粒pUB110、pE194、pTA1060、以及pAMβ1的復(fù)制起點(diǎn)?？梢詫⒈景l(fā)明的多核苷酸的多于一個拷貝插入宿主細(xì)胞中以增加多肽的產(chǎn)生。多核苷酸拷貝數(shù)的增加可通過如下方法獲得：將至少一個額外拷貝的序列整合入宿主細(xì)胞基因組，或?qū)⒖蓴U(kuò)增的選擇性標(biāo)記基因包括于多核苷酸，其中可通過在合適的選擇劑(selectableagent)存在下培養(yǎng)細(xì)胞來選擇含有選擇性標(biāo)記基因的擴(kuò)增拷貝，且由此含有多核苷酸的額外拷貝的細(xì)胞。用于連接以上所述的元件以構(gòu)建本發(fā)明的重組表達(dá)載體的程序是本領(lǐng)域的普通技術(shù)人員熟知的(參見，例如，薩姆布魯克(Sambrook)等人，1989，同上)。宿主細(xì)胞本發(fā)明還涉及重組宿主細(xì)胞，其包含本發(fā)明的多核苷酸可操作地連接于一個或多個指導(dǎo)本發(fā)明變體的產(chǎn)生的調(diào)控序列。因此，本發(fā)明涉及一種包含編碼一種變體的多核苷酸的重組宿主細(xì)胞，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性，其中該多核苷酸可操作地連接至一個或多個控制序列，所述控制序列指導(dǎo)本發(fā)明的變體的生產(chǎn)。將包括多核苷酸的構(gòu)建體或載體引入宿主細(xì)胞中，這樣使得該構(gòu)建體或載體被維持作為染色體整合體或作為自主復(fù)制的染色體外載體，如早前所述。術(shù)語“宿主細(xì)胞”涵蓋由于復(fù)制過程中發(fā)生的突變與親本細(xì)胞不同的親本細(xì)胞的任何后代。宿主細(xì)胞的選擇在很大程度上取決于編碼該多肽的基因及其來源。該宿主細(xì)胞可以是有用于重組產(chǎn)生本發(fā)明的多肽的任何細(xì)胞，例如原核細(xì)胞或真核細(xì)胞。原核宿主細(xì)胞可以是任何革蘭氏陽性或革蘭氏陰性細(xì)菌。革蘭氏陽性細(xì)菌包括但不限于芽孢桿菌屬、梭菌屬、腸球菌屬、土芽孢桿菌屬、乳桿菌屬、乳球菌屬、海洋芽孢桿菌屬、葡萄球菌屬、鏈球菌屬、以及鏈霉菌屬。革蘭氏陰性細(xì)菌包括但不限于彎曲桿菌屬、大腸桿菌、黃桿菌屬、梭桿菌屬、螺桿菌屬、泥桿菌屬、奈瑟氏菌屬、假單胞菌屬、沙門氏菌屬、以及脲原體屬。細(xì)菌宿主細(xì)胞可以是任何芽孢桿菌屬細(xì)胞，包括但不限于：嗜堿芽孢桿菌、解淀粉芽孢桿菌、短芽孢桿菌、環(huán)狀芽孢桿菌、克勞氏芽孢桿菌、凝結(jié)芽孢桿菌、堅(jiān)硬芽孢桿菌、燦爛芽孢桿菌、遲緩芽孢桿菌、地衣芽孢桿菌、巨大芽孢桿菌、短小芽孢桿菌、嗜熱脂肪芽孢桿菌、枯草芽孢桿菌以及蘇云金芽孢桿菌細(xì)胞。細(xì)菌宿主細(xì)胞還可以是任何鏈球菌屬細(xì)胞，包括但不限于：似馬鏈球菌、釀膿鏈球菌、乳房鏈球菌以及馬鏈球菌獸瘟亞種細(xì)胞。細(xì)菌宿主細(xì)胞還可以是任何鏈霉菌屬細(xì)胞，包括但不限于：不產(chǎn)色鏈霉菌、除蟲鏈霉菌、天藍(lán)鏈霉菌、灰色鏈霉菌、以及淺青紫鏈霉菌細(xì)胞。將DNA引入芽孢桿菌屬細(xì)胞中可通過以下來實(shí)現(xiàn)：原生質(zhì)體轉(zhuǎn)化(參見例如，張(Chang)和科恩(Cohen)，1979，分子遺傳學(xué)與基因組學(xué)(Mol.Gen.Genet.)168:111-115)、感受態(tài)細(xì)胞轉(zhuǎn)化(參見例如，楊格(Young)和斯皮宰曾(Spizizen)，1961，細(xì)菌學(xué)雜志(J.Bacteriol.)81:823-829；或杜拜努(Dubnau)以及大衛(wèi)杜夫-阿貝爾森(Davidoff-Abelson)，1971，分子生物學(xué)雜志(J.Mol.Biol.)56:209-221)、電穿孔(參見例如，茂川(Shigekawa)和道爾(Dower)，1988，生物技術(shù)(Biotechniques)6:742-751)、或者接合(參見例如，克勒(Koehler)和索恩(Thorne)，1987，細(xì)菌學(xué)雜志169:5271-5278)。將DNA引入大腸桿菌細(xì)胞中可通過以下來實(shí)現(xiàn)：原生質(zhì)體轉(zhuǎn)化(參見例如，哈納汗(Hanahan)，1983，分子生物學(xué)雜志(J.Mol.Biol.)166:557-580)或電穿孔(參見例如，道爾(Dower)等人，1988，核酸研究(NucleicAcidsRes.)16:6127-6145)。將DNA引入鏈霉菌屬細(xì)胞中可通過以下來實(shí)現(xiàn)：原生質(zhì)體轉(zhuǎn)化、電穿孔(參見例如，貢(Gong)等人，2004，葉線形微生物學(xué)(FoliaMicrobiol.)(Praha(布拉格))49:399-405)、接合(參見例如，馬佐迪耶(Mazodier)等人，1989，細(xì)菌學(xué)雜志(J.Bacteriol.)171:3583-3585)、或轉(zhuǎn)導(dǎo)(參見例如，伯克(Burke)等人，2001，美國國家科學(xué)院院刊(Proc.Natl.Acad.Sci.USA)98:6289-6294)。將DNA引入假單孢菌屬細(xì)胞中可通過以下來實(shí)現(xiàn)：電穿孔(參見例如，蔡(Choi)等人，2006，微生物學(xué)方法雜志(J.Microbiol.Methods)64:391-397)或接合(參見例如，皮內(nèi)多(Pinedo)和斯梅茨(Smets)，2005，應(yīng)用與環(huán)境微生物學(xué)(Appl.Environ.Microbiol.)71:51-57)。將DNA引入鏈球菌屬細(xì)胞中可通過以下來實(shí)現(xiàn)：天然感受態(tài)(參見，例如，佩里(Perry)和藏滿(Kuramitsu)，1981，感染與免疫(Infect.Immun.)32:1295-1297)、原生質(zhì)體轉(zhuǎn)化(參見，例如，凱特(Catt)和喬力克(Jollick)，1991，微生物學(xué)(Microbios)68:189-207)、電穿孔(參見，例如，巴克利(Buckley)等人，1999，應(yīng)用與環(huán)境微生物學(xué)(Appl.Environ.Microbiol.)65:3800-3804)、或者接合(參見，例如，克萊威爾(Clewell)，1981，微生物學(xué)評論(Microbiol.Rev.)45:409-436)。然而，可以使用本領(lǐng)域已知的用于將DNA引入宿主細(xì)胞中的任何方法。宿主細(xì)胞還可以是真核細(xì)胞，如哺乳動物、昆蟲、植物、或真菌細(xì)胞。該宿主細(xì)胞可以是真菌細(xì)胞。如在此使用的“真菌”包括子囊菌門(Ascomycota)、擔(dān)子菌門(Basidiomycota)、壺菌門(Chytridiomycota)、以及接合菌門(Zygomycota)、連同卵菌門(Oomycota)和全部有絲分裂孢子真菌(如由霍克斯沃思(Hawksworth)等人在安斯沃思和拜斯比真菌詞典(AinsworthandBisby’sDictionaryofTheFungi)，第8版，1995，國際應(yīng)用生物科學(xué)中心(CABInternational)，大學(xué)出版社(UniversityPress)，英國劍橋(Cambridge，UK)中進(jìn)行定義的)。該真菌宿主細(xì)胞可以是酵母細(xì)胞。如在此使用的“酵母”包括產(chǎn)子嚢酵母(內(nèi)孢霉目)、產(chǎn)擔(dān)子酵母和屬于半知菌類(芽孢綱)的酵母。由于酵母的分類在將來可能有變化，出于本發(fā)明的目的，酵母應(yīng)如酵母生物學(xué)和活動性(BiologyandActivitiesofYeast)(斯金納(Skinner)、帕斯莫爾(Passmore)、以及達(dá)文波特(Davenport)編輯，應(yīng)用細(xì)菌學(xué)學(xué)會討論會(Soc.App.Bacteriol.Symposium)系列第9期，1980)所述地進(jìn)行定義。酵母宿主細(xì)胞可以是假絲酵母屬、漢遜酵母屬、克魯弗酵母屬、畢赤酵母屬、酵母屬、裂殖酵母屬、或耶氏酵母屬細(xì)胞，如乳酸克魯弗酵母(Kluyveromyceslactis)、卡爾酵母、釀酒酵母、糖化酵母、道格拉氏酵母、克魯弗酵母、諾地酵母、卵形酵母、或解脂耶氏酵母(Yarrowialipolytica)細(xì)胞。生產(chǎn)方法本發(fā)明還涉及產(chǎn)生本發(fā)明的多肽的方法，這些方法包括(a)在有益于產(chǎn)生該多肽的條件下培養(yǎng)一種本發(fā)明的重組宿主細(xì)胞；并且可任選地(b)回收該多肽。因此，本發(fā)明涉及生產(chǎn)一種變體的方法，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性，其中該方法包括以下步驟：(i)在有利于產(chǎn)生該變體的條件下培養(yǎng)包含表達(dá)載體、編碼該變體的多核苷酸或核酸構(gòu)建體的重組宿主細(xì)胞；并且可任選地(b)回收該變體。這些宿主細(xì)胞是在適合于使用本領(lǐng)域中已知的方法產(chǎn)生該多肽的一種營養(yǎng)培養(yǎng)基中培養(yǎng)的。例如，可以通過在適合的培養(yǎng)基中和在允許表達(dá)和/或分離該多肽的條件下，進(jìn)行搖瓶培養(yǎng)，或者在實(shí)驗(yàn)室或工業(yè)發(fā)酵罐中進(jìn)行小規(guī)模或大規(guī)模發(fā)酵(包括連續(xù)、分批、分批補(bǔ)料、或固態(tài)發(fā)酵)來培養(yǎng)細(xì)胞。該培養(yǎng)是使用本領(lǐng)域中已知的程序，在一種適合營養(yǎng)培養(yǎng)基中發(fā)生，該培養(yǎng)基包括碳和氮來源及無機(jī)鹽。適合的培養(yǎng)基可從商業(yè)供應(yīng)商獲得或可以根據(jù)公開的組成(例如，在美國典型培養(yǎng)物保藏中心的目錄中)制備。如果多肽分泌到該營養(yǎng)培養(yǎng)基中，那么可直接從培養(yǎng)基中回收多肽。如果多肽不被分泌，那么其可從細(xì)胞裂解液中進(jìn)行回收?？梢允褂锰禺愋葬槍哂笑?淀粉酶活性的多肽的本領(lǐng)域已知的方法來檢測該多肽。這些檢測方法包括但不限于，特異性抗體的使用、酶產(chǎn)物的形成或酶底物的消失。例如，可以使用酶測定來確定該多肽的活性。可以使用本領(lǐng)域已知的方法來回收多肽。例如，該多肽可以通過常規(guī)程序，包括但不限于，收集、離心、過濾、提取、噴霧干燥、蒸發(fā)或沉淀，從該營養(yǎng)培養(yǎng)基回收。在一方面，回收包含該多肽的發(fā)酵液?？梢酝ㄟ^本領(lǐng)域中已知的多種程序來純化該多肽以獲得基本上純的多肽，這些程序包括但不限于：色譜法(例如，離子交換色譜、親和色譜、疏水作用色譜、色譜聚焦、以及尺寸排阻色譜)、電泳程序(例如，制備型等電點(diǎn)聚焦)、差別溶解度(例如，硫酸銨沉淀)、SDS-PAGE、或提取(參見例如，蛋白質(zhì)純化(ProteinPurification)，詹森(Janson)和賴登(Ryden)編輯，VCH出版社(VCHPublishers)，紐約，1989)。在替代性方面中，沒有回收該多肽，而是將表達(dá)該多肽的本發(fā)明的宿主細(xì)胞用作該多肽的來源。發(fā)酵液配制品或細(xì)胞組合物本發(fā)明還涉及包含本發(fā)明的多肽的發(fā)酵液配制品或細(xì)胞組合物。因此，本發(fā)明涉及包含一種變體的發(fā)酵液配制品或細(xì)胞組合物，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性。該發(fā)酵液產(chǎn)物進(jìn)一步包括用于發(fā)酵過程的另外的成分，如例如細(xì)胞(包括，含有用來產(chǎn)生感興趣的多肽的編碼本發(fā)明的多肽的基因的宿主細(xì)胞)、細(xì)胞碎片、生物質(zhì)、發(fā)酵介質(zhì)和/或發(fā)酵產(chǎn)物。在一些實(shí)施例中，該組合物是含有一種或多種有機(jī)酸、殺滅的細(xì)胞和/或細(xì)胞碎片以及培養(yǎng)基的細(xì)胞殺滅的全培養(yǎng)液。如在此使用的術(shù)語“發(fā)酵液”是指由細(xì)胞發(fā)酵產(chǎn)生、不經(jīng)歷或經(jīng)歷最低限的回收和/或純化的制劑。例如，當(dāng)微生物培養(yǎng)物生長至飽和，在碳限制條件下孵育以允許蛋白質(zhì)合成(例如，由宿主細(xì)胞進(jìn)行酶的表達(dá))并且分泌到細(xì)胞培養(yǎng)基中時，產(chǎn)生發(fā)酵液。所述發(fā)酵液可以包含在發(fā)酵終止時得到的發(fā)酵材料的未分級或分級的內(nèi)含物。典型地，發(fā)酵液是未分級的并且包括在例如通過離心除去微生物細(xì)胞(例如，絲狀真菌細(xì)胞)后存在的耗盡的培養(yǎng)基和細(xì)胞碎片。在一些實(shí)施例中，該發(fā)酵液包含耗盡的細(xì)胞培養(yǎng)基、胞外酶、以及有活力的和/或無活力的微生物細(xì)胞。在一個實(shí)施例中，該發(fā)酵液配制品和細(xì)胞組合物包括第一有機(jī)酸組分(包括至少一種1-5碳的有機(jī)酸和/或其鹽)以及第二有機(jī)酸組分(包括至少一種6碳或更多碳的有機(jī)酸和/或其鹽)。在具體實(shí)施例中，該第一有機(jī)酸組分是乙酸、甲酸、丙酸、其鹽，或前述兩種或更多種的混合物；并且該第二有機(jī)酸組分是苯甲酸、環(huán)己烷羧酸、4-甲基戊酸、苯乙酸、其鹽，或前述兩種或更多種的混合物。在一個方面，該組合物包含一種或多種有機(jī)酸，并且任選地進(jìn)一步包含殺滅的細(xì)胞和/或細(xì)胞碎片。在一個實(shí)施例中，從細(xì)胞殺滅的全培養(yǎng)液中去除這些殺滅的細(xì)胞和/或細(xì)胞碎片，以提供不含這些組分的組合物。這些發(fā)酵液配制品或細(xì)胞組合物可以進(jìn)一步包括防腐劑和/或抗微生物(例如，抑菌)劑，包括但不限于山梨醇、氯化鈉、山梨酸鉀、以及本領(lǐng)域中已知的其他試劑。該細(xì)胞殺滅的全培養(yǎng)液或組合物可以包含在發(fā)酵結(jié)束時得到的發(fā)酵材料的未分級的內(nèi)容物。典型地，該細(xì)胞殺滅的全培養(yǎng)液或組合物包含用過的培養(yǎng)基以及在微生物細(xì)胞(例如，絲狀真菌細(xì)胞)生長至飽和、在碳限制條件下孵育以允許蛋白合成之后存在的細(xì)胞碎片。在一些實(shí)施例中，細(xì)胞殺滅的全培養(yǎng)液或組合物含有用過的細(xì)胞培養(yǎng)基、胞外酶和殺滅的絲狀真菌細(xì)胞。在一些實(shí)施例中，可以使用本領(lǐng)域已知的方法來使細(xì)胞殺滅的全培養(yǎng)液或組合物中存在的微生物細(xì)胞透性化和/或裂解。如在此描述的全培養(yǎng)液或細(xì)胞組合物典型地是液體，但是可以含有不溶性組分，例如殺滅的細(xì)胞、細(xì)胞碎片、培養(yǎng)基組分和/或一種或多種不溶性酶。在一些實(shí)施例中，可以除去不溶性組分，以提供一種澄清的液體組合物。可以通過描述于WO90/15861或WO2010/096673中的方法生產(chǎn)本發(fā)明的全發(fā)酵液配制品和細(xì)胞組合物。酶組合物本發(fā)明還涉及包括本發(fā)明的α-淀粉酶變體的組合物。因此，本發(fā)明涉及包含一種變體的組合物，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體具有α-淀粉酶活性。優(yōu)選地，所述組合物富含這種多肽。術(shù)語“富含”指示該組合物的α-淀粉酶活性已經(jīng)增加，例如，以至少1.1的富集因子。這些組合物可以包含本發(fā)明的多肽作為主要酶組分，例如單組分組合物?？商娲?，這些組合物可以包含多種酶活性，如一種或多種(例如，若干種)選自下組的酶，該組由以下各項(xiàng)組成：水解酶、異構(gòu)酶、連接酶、裂解酶、氧化還原酶、或轉(zhuǎn)移酶，例如，α-半乳糖苷酶、α-葡糖苷酶、氨肽酶、淀粉酶、β-半乳糖苷酶、β-葡糖苷酶、β-木糖苷酶、糖酶、羧肽酶、過氧化氫酶、纖維二糖水解酶、纖維素酶、殼多糖酶、角質(zhì)酶、環(huán)糊精葡萄糖基轉(zhuǎn)移酶、脫氧核糖核酸酶、內(nèi)切葡聚糖酶、酯酶、葡糖淀粉酶、轉(zhuǎn)化酶、漆酶、脂肪酶、甘露糖苷酶、變聚糖酶、氧化酶、果膠分解酶、過氧化物酶、植酸酶、多酚氧化酶、蛋白水解酶、核糖核酸酶、轉(zhuǎn)谷氨酰胺酶、或木聚糖酶。這些組合物可根據(jù)本領(lǐng)域已知的方法制備并且可以是液體或干燥組合物的形式?？梢愿鶕?jù)本領(lǐng)域中已知的方法穩(wěn)定這些組合物。洗滌劑組合物在一個實(shí)施例中，本發(fā)明針對以下洗滌劑組合物，這些洗滌劑組合物包括與一種或多種另外的清潔組合物組分組合的本發(fā)明的α-淀粉酶變體。因此，本發(fā)明涉及包含一種變體的洗滌劑組合物，該變體包括(a)在對應(yīng)于SEQIDNO:1的成熟多肽的位置R181、G182、H183和G184的兩個或多個位置處的缺失和/或取代，以及(b)在一個或多個位置處的取代，所述取代對應(yīng)于位置1、2、3、4、5、7、9、16、25、26、28、36、40、47、48、50、51、56、67、72、73、75、85、86、87、98、109、112、113、118、119、125、128、133、134、136、140、141、142、144、146、149、155、158、160、165、167、169、171、172、173、174、179、181、182、184、186、192、193、194、195、197、200、202、204、206、208、210、211、112、213、214、215、217、218、219、220、226、241、243、246、255、265、268、269、270、273、274、276、280、282、283、291、294、295、296、299、302、303、304、305、311、315、319、320、321、323、324、330、336、343、345、346、349、351、354、355、361、363、364、376、380、383、391、402、405、406、408、410、411、414、415、416、418、421、423、424、427、429、430、431、438、439、442、444、446、447、449、457、463、464、465、466、467、469、471、473、474、476、477、478、482、或483，和/或在對應(yīng)于SEQIDNO:1的1、2、3、4、5、172、173或174的一個或多個位置處的缺失，其中該α-淀粉酶變體與具有SEQIDNO:1的氨基酸序列的多肽具有至少95％序列一致性但小于100％序列一致性，并且其中該變體組合一種或多種另外的清潔組合物組分具有α-淀粉酶活性。在一個實(shí)施例中，該洗滌劑是液體洗滌劑組合物。在另一個實(shí)施例中，該洗滌劑組合物是粉末狀洗滌劑組合物。該洗滌劑組合物可以是衣物洗滌劑組合物或餐具洗滌洗滌劑組合物。另外的組分的選擇在普通技術(shù)人員技術(shù)內(nèi)并且包括常規(guī)成分，包括以下列出的示例性、非限制性組分。對于織物護(hù)理，組分的選擇可以包括以下考慮：有待清潔的織物的類型、污漬的類型和/或程度、進(jìn)行清潔時的溫度、以及洗滌劑產(chǎn)品的配制。盡管根據(jù)具體的功能性對以下提及的組分由通用標(biāo)題進(jìn)行分類，但是這并不被解釋為限制，因?yàn)槿鐚⒈黄胀夹g(shù)人員所理解，一種組分可以包括另外的功能性。在本發(fā)明的一個實(shí)施例中，可以將本發(fā)明的變體以對應(yīng)于以下各項(xiàng)的量添加至一種洗滌劑組合物中：每升洗滌液體0.001-100mg的蛋白質(zhì)，如0.01-100mg的蛋白質(zhì)，優(yōu)選是0.005-50mg的蛋白質(zhì)，更優(yōu)選是0.01-25mg的蛋白質(zhì)，甚至更優(yōu)選是0.05-10mg的蛋白質(zhì)，最優(yōu)選是0.05-5mg的蛋白質(zhì)，并且甚至最優(yōu)選是0.01-1mg的蛋白質(zhì)。用于在自動洗碗機(jī)(ADW)中使用的組合物例如可以包括按該組合物的重量計(jì)0.0001％-50％，例如0.001％-20％，例如0.01％-10％，例如0.05％-5％的酶蛋白。用于在洗衣造粒(laundrygranulation)中使用的組合物例如可以包含按該組合物的重量計(jì)0.0001％-50％，例如0.001％-20％，例如0.01％-10％，例如0.05％-5％的酶蛋白。用于在洗衣液中使用的組合物例如可以包括按該組合物的重量計(jì)0.0001％-10％，例如0.001％-7％，例如0.1％-5％的酶蛋白?？梢允褂贸Ｒ?guī)穩(wěn)定劑穩(wěn)定本發(fā)明的一種或多種酶，這些常規(guī)穩(wěn)定劑例如是多元醇，例如丙二醇或甘油、糖或糖醇、乳酸、硼酸或硼酸衍生物，例如芳香族硼酸酯，或苯基硼酸衍生物，例如4-甲酰苯基硼酸，并且可以如在例如WO92/19709和WO92/19708中所述配制該組合物。在某些市場中，不同洗滌條件并且就其本身而言，使用不同類型的洗滌劑。這披露于例如EP1025240中。例如，在亞洲(日本)使用低的洗滌劑濃度體系，而美國使用中等洗滌劑濃度體系，并且歐洲使用高的洗滌劑濃度體系。低的洗滌劑濃度體系包含以下洗滌劑，其中在洗滌水中存在少于約800ppm的洗滌劑組分。日本洗滌劑典型地被認(rèn)為是低的洗滌劑濃度體系，因?yàn)樗鼈兙哂写嬖谟谙礈焖械拇蠹s667ppm的洗滌劑組分。中等洗滌劑濃度體系包含以下洗滌劑，其中在洗滌水中存在約800ppm與約2000ppm之間的洗滌劑組分。北美洗滌劑通常被認(rèn)為是中等洗滌劑濃度體系，因?yàn)樗鼈兙哂写嬖谟谙礈焖械拇蠹s975ppm的洗滌劑組分。高的洗滌劑濃度體系包含以下洗滌劑，其中在洗滌水中存在多于約2000ppm的洗滌劑組分。歐洲洗滌劑通常被認(rèn)為是高的洗滌劑濃度體系，因?yàn)樵谙礈焖兴鼈兙哂写蠹s4500-5000ppm的洗滌劑組分。拉丁美洲洗滌劑通常是高泡沫磷酸鹽助洗劑洗滌劑并且在拉丁美洲使用的洗滌劑的范圍可以落入中等和高的洗滌劑濃度兩者中，因?yàn)樵谙礈焖兴鼈兊南礈靹┙M分的范圍從1500ppm至6000ppm。此類洗滌劑組合物都是本發(fā)明的實(shí)施例。本發(fā)明的多肽還可以結(jié)合到WO97/07202中所披露的洗滌劑配制品中，通過引用將其結(jié)合在此。下文中給出本發(fā)明的組合物的優(yōu)選用途的實(shí)例。可以基于本領(lǐng)域已知的方法來確定組合物的劑量和使用該組合物的其他條件。表面活性劑洗滌劑組合物可以包括一種或多種表面活性劑，它們可以是陰離子的和/或陽離子的和/或非離子的和/或半極性的和/或兼性離子的或其混合物。在一個具體實(shí)施例中，洗滌劑組合物包括一種或多種非離子型表面活性劑和一種或多種陰離子表面活性劑的混合物。這種或這些表面活性劑典型地以按重量計(jì)從約0.1％至60％的水平存在，例如約1％至約40％、或約3％至約20％、或約3％至約10％?；谒Ｍ那鍧崙?yīng)用來選擇這種或這些表面活性劑，并且這種或這些表面活性劑包括本領(lǐng)域中已知的任何一種或多種常規(guī)表面活性劑?？梢岳帽绢I(lǐng)域中已知的用于在洗滌劑中使用的任何表面活性劑。當(dāng)包含在其中時，所述去污劑通常將會含有按重量計(jì)約1％至約40％，例如約5％至約30％，包括約5％至約15％，或約20％至約25％的陰離子型表面活性劑。陰離子表面活性劑的非限制性實(shí)例包括硫酸鹽和磺酸鹽，具體地說是直鏈烷基苯磺酸鹽(LAS)、LAS的異構(gòu)體、支鏈烷基苯磺酸鹽(BABS)、苯基鏈烷磺酸鹽、α-烯烴磺酸鹽(AOS)、烯烴磺酸鹽、鏈烯烴磺酸鹽、鏈烷-2,3-二基雙(硫酸鹽)、羥基鏈烷磺酸鹽以及二磺酸鹽、烷基硫酸鹽(AS)(如十二烷基硫酸鈉(SDS))、脂肪醇硫酸鹽(FAS)、伯醇硫酸鹽(PAS)、醇醚硫酸鹽(AES或AEOS或FES，也被稱為醇乙氧基硫酸鹽或脂肪醇醚硫酸鹽)、仲鏈烷磺酸鹽(SAS)、石蠟烴磺酸鹽(PS)、酯磺酸鹽、磺化的脂肪酸甘油酯、α-磺酸基脂肪酸甲酯(α-SFMe或SES)(包括甲酯磺酸鹽(MES))、烷基琥珀酸或烯基琥珀酸、十二烯基/十四烯基琥珀酸(DTSA)、氨基酸的脂肪酸衍生物、磺酸基琥珀酸或皂的二酯和單酯、及其組合。當(dāng)被包括在其中時，洗滌劑將通常包含按重量計(jì)從約0％至約40％的陽離子表面活性劑。陽離子表面活性劑的非限制性實(shí)例包括烷基二甲基乙醇季胺(ADMEAQ)、十六烷基三甲基溴化銨(CTAB)、二甲基二硬脂酰氯化銨(DSDMAC)、以及烷基芐基二甲基銨、烷基季銨化合物、烷氧基化季銨(AQA)化合物及其組合。當(dāng)包括在其中時，去污劑通常會含有按重量計(jì)約0.2％-約40％，例如約0.5％-約30％，特別是約1％-約20％、約3％-約10％，例如約3％-約5％、或約8％-約12％的非離子型表面活性劑。非離子型表面活性劑的非限制性實(shí)例包括醇乙氧基化物(AE或AEO)、醇丙氧基化物、丙氧基化的脂肪醇(PFA)、烷氧基化的脂肪酸烷基酯(例如乙氧基化的和/或丙氧基化的脂肪酸烷基酯)、烷基酚乙氧基化物(APE)、壬基酚乙氧基化物(NPE)、烷基多糖苷(APG)、烷氧基化胺、脂肪酸單乙醇酰胺(FAM)、脂肪酸二乙醇酰胺(FADA)、乙氧基化的脂肪酸單乙醇酰胺(EFAM)、丙氧基化的脂肪酸單乙醇酰胺(PFAM)、多羥基烷基脂肪酸酰胺、或葡萄糖胺的N-?；鵑-烷基衍生物(葡糖酰胺(GA)、或脂肪酸葡糖酰胺(FAGA))、連同在SPAN和TWEEN商品名下可獲得的產(chǎn)品及其組合。當(dāng)被包括在其中時，洗滌劑將通常包含按重量計(jì)從約0％至約40％的半極性表面活性劑。半極性表面活性劑的非限制性實(shí)例包括氧化胺(AO)，例如烷基二甲基氧化胺、N-(椰油基烷基)-N,N-二甲基氧化胺和N-(牛油-烷基)-N,N-雙(2-羥乙基)氧化胺、脂肪酸鏈烷醇酰胺和乙氧基化的脂肪酸鏈烷醇酰胺及其組合。當(dāng)被包括在其中時，洗滌劑將通常包含按重量計(jì)從約0％至約40％的兼性離子表面活性劑。兼性離子表面活性劑的非限制性實(shí)例包括甜菜堿、烷基二甲基甜菜堿、磺基甜菜堿及其組合。本發(fā)明的洗滌劑組合物還包括如在US20130072416或US20130072415中所披露的類異戊二烯表面活性劑中的一個或多個。助水溶劑助水溶劑是如下化合物，該化合物在水性溶液中溶解疏水化合物(或相反地，在非極性環(huán)境中的極性物質(zhì))。一般地，助水溶物具有親水和疏水兩種特征(所謂的兩親性質(zhì)，如由表面活性劑已知的)；然而，助水溶劑的分子結(jié)構(gòu)一般不利于自發(fā)性自聚集，參見例如通過霍奇登(Hodgdon)和卡勒(Kaler)(2007)，膠體&界面科學(xué)新見(CurrentOpinioninColloid&InterfaceScience)12:121-128的綜述。助水溶劑并不顯示臨界濃度，高于該濃度就會發(fā)生如對表面活性劑而言所發(fā)現(xiàn)的自聚集以及脂質(zhì)形成膠束、薄層或其他很好地定義的中間相。相反，許多助水溶物顯示連續(xù)類型的聚集過程，其中聚集物的大小隨著濃度增加而增長。然而，很多助水溶劑改變了包括極性和非極性特征的物質(zhì)的系統(tǒng)(包括水、油、表面活性劑、和聚合物的混合物)的相行為、穩(wěn)定性、和膠體特性。助水溶劑常規(guī)地在從藥學(xué)(pharma)、個人護(hù)理、食品到技術(shù)應(yīng)用的各個產(chǎn)業(yè)中應(yīng)用。助水溶劑在洗滌劑組合物中的使用允許例如更濃的表面活性劑配制品(如在通過去除水而壓縮液體洗滌劑的過程中)而不引起不希望的現(xiàn)象，例如相分離或高粘度。去污劑可以含有按重量計(jì)0-5％、例如0.5％-約5％或約3％-約5％的助水溶劑?？梢岳帽绢I(lǐng)域中已知的用于在洗滌劑中使用的任何助水溶劑。助水溶劑的非限制性實(shí)例包括苯磺酸鈉、對甲苯磺酸鈉(STS)、二甲苯磺酸鈉(SXS)、枯烯磺酸鈉(SCS)、傘花烴磺酸鈉、氧化胺、醇和聚乙二醇醚、羥基萘甲酸鈉、羥基萘磺酸鈉、乙基己基磺酸鈉及其組合。助洗劑和共助洗劑該洗滌劑組合物可以包含按重量計(jì)約0-65％，例如約10％至約40％的洗滌劑助洗劑或共助洗劑、或其混合物。在洗滌餐具洗滌劑中，助洗劑的水平典型地是40％-65％，特別是50％-65％。助洗劑和/或共助洗劑可以具體是形成具有Ca和Mg的水溶性復(fù)合物的螯合劑(chelatingagent)(即螯合劑(chelator))?？梢岳帽绢I(lǐng)域中已知的用于在衣物洗滌劑中使用的任何助洗劑和/或共-助洗劑。助洗劑的非限制性實(shí)例包括沸石、二磷酸鹽(焦磷酸鹽)、三磷酸鹽例如三磷酸鈉(STP或STPP)、碳酸鹽例如碳酸鈉、可溶性硅酸鹽例如硅酸鈉、層狀硅酸鹽(例如來自赫斯特公司(Hoechst)的SKS-6)、乙醇胺例如2-氨基乙-1-醇(MEA)、二乙醇胺(DEA，也稱為亞氨基二乙醇)、三乙醇胺(TEA，也稱為2,2’,2”-次氨基三乙醇)、以及羧甲基菊粉(CMI)及其組合。洗滌劑組合物還可以包含按重量計(jì)0-50％，例如約10％至約40％的洗滌劑共助洗劑、或其混合物。洗滌劑組合物可以單獨(dú)地包括一種共助洗劑，或與一種助洗劑，例如沸石助洗劑組合。共助洗劑的非限制性實(shí)例包括聚丙烯酸酯的均聚物或其共聚物，例如聚(丙烯酸)(PAA)或共聚(丙烯酸/馬來酸)(PAA/PMA)。另外的非限制性實(shí)例包括檸檬酸鹽，螯合劑，例如氨基羧酸鹽、氨基多羧酸鹽和膦酸鹽，以及烷基-或烯基琥珀酸。另外的具體實(shí)例包括2,2’,2”-次氨基三乙酸(NTA)、乙二胺四乙酸(EDTA)、二亞乙基三胺五乙酸(DTPA)、亞氨基二丁二酸(iminodisuccinicacid)(IDS)、乙二胺-N,N’-二丁二酸(EDDS)、甲基甘氨酸二乙酸(MGDA)、谷氨酸-N,N-二乙酸(GLDA)、1-羥基乙烷-1,1-二膦酸(HEDP)、乙二胺四-(亞甲基膦酸)(EDTMPA)、二亞乙基三胺五(亞甲基膦酸)(DTMPA或DTPMPA)、N-(2-羥乙基)亞氨基二乙酸(EDG)、天冬氨酸-N-單乙酸(ASMA)、天冬氨酸-N,N-二乙酸(ASDA)、天冬氨酸-N-單丙酸(ASMP)、亞氨基二丁二酸(iminodisuccinicacid)(IDA)、N-(2-磺甲基)-天冬氨酸(SMAS)、N-(2-磺乙基)-天冬氨酸(SEAS)、N-(2-磺甲基)-谷氨酸(SMGL)、N-(2-磺乙基)-谷氨酸(SEGL)、N-甲基亞氨基二乙酸(MIDA)、α-丙氨酸-N,N-二乙酸(α-ALDA)、絲氨酸-N,N-二乙酸(SEDA)、異絲氨酸-N,N-二乙酸(ISDA)、苯丙氨酸-N,N-二乙酸(PHDA)、鄰氨基苯甲酸-N,N-二乙酸(ANDA)、磺胺酸-N,N-二乙酸(SLDA)、牛磺酸-N,N-二乙酸(TUDA)以及磺甲基-N,N-二乙酸(SMDA)、N-(2-羥乙基)-亞乙基二胺-N,N’,N’-三乙酸鹽(HEDTA)、二乙醇甘氨酸(DEG)、二亞乙基三胺五(亞甲基膦酸)(DTPMP)、氨基三(亞甲基膦酸)(ATMP)及其組合和鹽。其他示例性助洗劑和/或共助洗劑描述于例如WO09/102854、US5977053中。螯合劑(Chelatingagent)或螯合劑(chelator)是可與特定的金屬離子形成分子的化學(xué)物，從而使這些離子失活使其不能與其他元素進(jìn)行反應(yīng)，由此是通過形成螯合物而抑制化學(xué)活性的一種結(jié)合劑。螯合是在配體與單一中心原子之間形成或存在的兩種或更多種單獨(dú)的結(jié)合。配體可以是任何有機(jī)化合物、硅酸鹽或磷酸鹽。在本文上下文中，術(shù)語“螯合劑(chelatingagent)”包括螯合劑(chelant)、螯合劑(chelatingagent)、螯合劑(chelatingagent)、絡(luò)合劑(complexingagent)、或可與如鈣和鎂等金屬離子形成水溶性復(fù)合物的螯合劑(sequesteringagent)。螯合作用描述螯合配體對金屬離子的親和力相對于類似的一組非螯合配體對相同金屬的親和力的增強(qiáng)。螯合劑具有與金屬離子特別是鈣(Ca2+)離子的結(jié)合能力，并廣泛應(yīng)用于洗滌劑，和一般用于洗滌如洗衣或洗碟的組合物。然而，螯合劑自身呈現(xiàn)出抑制酶活性。在本申請中，術(shù)語螯合劑(chelatingagent)與“絡(luò)合劑(complexingagent)”或“螯合劑(chelatingagent)”或“螯合劑(chelant)”互換使用。由于大多數(shù)α-淀粉酶具有鈣敏感性，螯合劑的存在可影響酶活性。α-淀粉酶的鈣敏感性可通過將給定α-淀粉酶在強(qiáng)螯合劑的存在下溫育，并分析該溫育對所述α-淀粉酶的活性的影響來確定。鈣敏感性α-淀粉酶會在溫育過程中喪失其活性的主要部分或全部。該螯合劑可以按一個量值存在于該組合物中，該量值為從0.0001wt％至20wt％、優(yōu)選地從0.01wt％至10wt％、更優(yōu)選地從0.1wt％至5wt％。強(qiáng)螯合劑可以是但不限于以下各項(xiàng)：乙二胺四乙酸(EDTA)、二亞乙基三胺五亞甲基膦酸(DTMPA、DTPMP)、羥基乙烷二膦酸(HEDP)、乙二胺N,N'-二丁二酸(EDDS)、甲基甘氨酸二乙酸(MGDA)、二亞乙基三胺五乙酸(DTPA)、丙烯二胺四乙酸(PDTA)、2-羥基吡啶-N-氧化物(HPNO)、甲基甘氨酸二乙酸(MGDA)、谷氨酸N,N-二乙酸(N,N-二羧基甲基谷氨酸四鈉鹽(GLDA)和次氨基三乙酸(NTA)或其混合物。螯合劑可以按它們的酸形式或鹽存在，優(yōu)選地，螯合劑可以作為鈉鹽、銨鹽或鉀鹽存在。表征螯合劑：如所提及的，螯合效應(yīng)(chelateeffect或chelatingeffect)描述了與相似的非螯合配體對于金屬離子的親和力相比，螯合配體對于相同的金屬離子具有增強(qiáng)的親和力。然而，該螯合作用的強(qiáng)度可通過多種類型的測定或測量方法決定，由此根據(jù)其螯合作用(或強(qiáng)度)對螯合劑進(jìn)行區(qū)分和排位。在一個測定中，螯合劑可以通過它們在pH8.0下將游離鈣離子(Ca2+)的濃度從2.0mM降低至0.10mM或更少的能力來表征，例如通過使用基于由M.K.納卡拉占(Nagarajan)等人，JAOCS，第61卷，第9期(1984年9月)，第1475-1478頁描述的方法的測試。供參考，一種螯合劑與以該螯合劑相等濃度的EDTA在pH下具有將游離鈣離子(Ca2+)濃度從2.0mM降低至0.10mM相同能力，則該螯合劑被稱為強(qiáng)螯合劑。漂白系統(tǒng)：所述洗滌劑可以包含按重量計(jì)0-20％，如約0％至約10％的漂白系統(tǒng)?？梢岳帽绢I(lǐng)域中已知的用于在衣物+餐具洗滌+I&I洗滌劑中使用的任何漂白系統(tǒng)。適合的漂白系統(tǒng)組分包括漂白催化劑、光漂白劑、漂白活化劑、過氧化氫源如過碳酸鈉和過硼酸鈉、預(yù)制的過酸和其混合物。適合的預(yù)成型過酸包括但不限于：過氧羧酸及鹽、過碳酸及鹽、過亞氨酸(perimidicacid)及鹽、過氧單硫酸及鹽(例如過硫酸氫鉀(Oxone(R))、及其混合物。漂白系統(tǒng)的非限制性實(shí)例包括基于過氧化物的漂白系統(tǒng)，該系統(tǒng)可以包括例如一種與過酸形成漂白活化劑組合的無機(jī)鹽，包括堿金屬鹽，例如過硼酸鹽(通常是單水合物或四水合物)、過碳酸鹽、過硫酸鹽、過磷酸鹽、過硅酸鹽的鈉鹽。術(shù)語漂白活化劑在此意指一種與過氧化物漂白劑(像過氧化氫)反應(yīng)以形成過酸的化合物。因此形成的過酸構(gòu)成活化的漂白劑。有待在此使用的適合漂白活化劑包括屬于酯酰胺、酰亞胺或酸酐類別的那些。適合的實(shí)例是四乙?；叶?TAED)、4-[(3,5,5-三甲基己酰)氧基]苯磺酸鈉(ISONOBS)、二過氧月桂酸、4-(十二?；趸?苯磺酸鹽(LOBS)、4-(癸?；趸?苯磺酸鹽、4-(癸酰基氧基)苯甲酸鹽(DOBS)、4-(壬?；趸?-苯磺酸鹽(NOBS)、和/或披露于WO98/17767中的那些。感興趣的漂白活化劑的具體家族披露于EP624154中并且在那個家族中特別優(yōu)選的是乙酰檸檬酸三乙酯(ATC)。ATC或短鏈甘油三酸酯(像三醋汀)具有以下優(yōu)點(diǎn)，它是環(huán)境友好的，因?yàn)樗罱K降解為檸檬酸和醇。此外，乙酰檸檬酸三乙酯和三醋汀在儲存時在產(chǎn)品中具有良好的水解穩(wěn)定性，并且它是一種有效的漂白活化劑。最后，ATC為洗衣添加劑提供一種良好的助洗能力?？商娲?，漂白系統(tǒng)可以包括例如酰胺、酰亞胺、或砜型的過氧酸。該漂白系統(tǒng)還可以包括過酸，例如6-(苯二甲酰亞氨基)過己酸(PAP)。該漂白系統(tǒng)還可以包括漂白催化劑。在一些實(shí)施例中，漂白組分可以是選自下組的有機(jī)催化劑，該組由以下各項(xiàng)組成：具有下式的有機(jī)催化劑：(iii)及其混合物；其中每個R1獨(dú)立地是包含從9至24個碳的支鏈烷基基團(tuán)或包含從11至24個碳的直鏈烷基基團(tuán)，優(yōu)選地，每個R1獨(dú)立地是包含從9至18個碳的支鏈烷基基團(tuán)或包含從11至18個碳的直鏈烷基基團(tuán)，更優(yōu)選地，每個R1獨(dú)立地選自下組，該組由以下各項(xiàng)組成：2-丙基庚基、2-丁基辛基、2-戊基壬基、2-己基癸基、正-十二烷基、正-十四烷基、正-十六烷基、正-十八烷基、異-壬基、異-癸基、異-十三基和異-十五烷基。其他示例性漂白系統(tǒng)描述于例如WO2007/087258、WO2007/087244、WO2007/087259以及WO2007/087242中。適合的光漂白劑可以例如是磺化的酞菁鋅。聚合物：所述洗滌劑可以包含按重量計(jì)0-10％，例如0.5％-5％、2％-5％、0.5％-2％或0.2％-1％的聚合物?？梢岳帽绢I(lǐng)域中已知的用于在洗滌劑中使用的任何聚合物。該聚合物可以作為如以上提到的共助洗劑起作用，或可以提供抗再沉積、纖維保護(hù)、污垢釋放、染料轉(zhuǎn)移抑制、油污清潔和/或防沫特性。一些聚合物可以具有多于一種的以上提到的特性和/或多于一種的以下提到的基序(motif)。示例性聚合物包括(羧甲基)纖維素(CMC)、聚(乙烯醇)(PVA)、聚(乙烯吡咯烷酮)(PVP)、聚(乙二醇)或聚(環(huán)氧乙烷)(PEG)、乙氧基化的聚(亞乙基亞胺)、羧甲基菊粉(CMI)、和聚羧化物，例如PAA、PAA/PMA、聚-天冬氨酸、和甲基丙烯酸月桂酯/丙烯酸共聚物、疏水修飾CMC(HM-CMC)和硅酮、對苯二甲酸和低聚乙二醇的共聚物、聚(對苯二甲酸乙二酯)和聚(氧乙烯對苯二甲酸乙二酯)的共聚物(PET-POET)、PVP、聚(乙烯基咪唑)(PVI)、聚(乙烯吡啶-N-氧化物)(PVPO或PVPNO)以及聚乙烯吡咯烷酮-乙烯基咪唑(PVPVI)。另外的示例性聚合物包括磺化的聚羧酸酯、聚環(huán)氧乙烷和聚環(huán)氧丙烷(PEO-PPO)以及乙氧基硫酸二季銨鹽。其他示例性聚合物披露于例如WO2006/130575中。也考慮了以上提到的聚合物的鹽?？椢镎{(diào)色劑：本發(fā)明的洗滌劑組合物還可以包括織物調(diào)色劑，例如當(dāng)配制在洗滌劑組合物中時，可以在織物與包括所述洗滌劑組合物的洗滌液體接觸時沉積在所述織物上并從而通過可見光吸收/反射來改變所述織物色彩的染料或色素。熒光增白劑發(fā)射至少一些可見光。相比之下，因?yàn)樗鼈兾罩辽僖徊糠挚梢姽夤庾V，所以織物調(diào)色劑改變表面的色彩。適合的織物調(diào)色劑包括染料和染料-粘土軛合物，并且還可以包括色素。適合的染料包括小分子染料和聚合物染料。適合的小分子染料包括選自下組的小分子染料，該組由落入顏色索引(ColourIndex)(C.I.)分類的以下染料組成：直接藍(lán)、直接紅、直接紫、酸性藍(lán)、酸性紅、酸性紫、堿性藍(lán)、堿性紫和堿性紅、或其混合物，例如描述于WO2005/03274、WO2005/03275、WO2005/03276和EP1876226中(將其通過引用而特此結(jié)合)。洗滌劑組合物優(yōu)選包括從約0.00003wt％至約0.2wt％、從約0.00008wt％至約0.05wt％、或甚至從約0.0001wt％至約0.04wt％的織物調(diào)色劑。該組合物可以包括從0.0001wt％至0.2wt％的織物調(diào)色劑，當(dāng)該組合物處于單位劑量袋的形式時，這可以是特別優(yōu)選的。適合的調(diào)色劑還披露于例如WO2007/087257和WO2007/087243中。另外的酶洗滌劑添加劑連同洗滌劑組合物可以包括一種或多種另外的酶，例如蛋白酶、脂肪酶、角質(zhì)酶、淀粉酶、糖酶、纖維素酶、果膠酶、甘露聚糖酶、阿拉伯糖酶、半乳聚糖酶、木聚糖酶、氧化酶，例如漆酶、和/或過氧化物酶。一般而言，一種或多種所選酶的特性應(yīng)與選定的洗滌劑相容(即，最適pH，與其他酶和非酶成分的相容性，等等)，并且該一種或多種酶應(yīng)以有效量存在。纖維素酶適合的纖維素酶包括細(xì)菌或真菌來源的那些。包括化學(xué)修飾的或蛋白質(zhì)工程化的突變體。適合的纖維素酶包括來自芽孢桿菌屬、假單胞菌屬、腐質(zhì)霉屬、鐮孢屬、梭孢殼菌屬、支頂孢屬的纖維素酶，例如披露于US4,435,307、US5,648,263、US5,691,178、US5,776,757以及WO89/09259中的由特異腐質(zhì)霉、嗜熱毀絲霉和尖孢鐮孢菌產(chǎn)生的真菌纖維素酶。特別適合的纖維素酶是具有顏色護(hù)理益處的堿性或中性纖維素酶。此類纖維素酶的實(shí)例是描述于EP0495257、EP0531372、WO96/11262、WO96/29397、WO98/08940中的纖維素酶。其他實(shí)例是例如描述于WO94/07998、EP0531315、US5,457,046、US5,686,593、US5,763,254、WO95/24471、WO98/12307以及WO99/001544中的那些纖維素酶變體。其他纖維素酶是具有以下序列的內(nèi)切-β-1,4-葡聚糖酶，該序列與WO2002/099091的SEQIDNO:2的位置1至位置773的氨基酸序列具有至少97％一致性，或家族44木葡聚糖酶，該木葡聚糖酶具有以下序列，該序列與WO2001/062903的SEQIDNO:2的位置40-559具有至少60％一致性?？缮藤彽睦w維素酶包括CelluzymeTM和CarezymeTM(諾維信公司(NovozymesA/S))、CarezymePremiumTM(諾維信公司)、CellucleanTM(諾維信公司)、CellucleanClassicTM(諾維信公司)、CellusoftTM(諾維信公司)、WhitezymeTM(諾維信公司)、ClazinaseTM和PuradaxHATM(杰能科國際公司(GenencorInternationalInc.))以及KAC-500(B)TM(花王株式會社(KaoCorporation))。甘露聚糖酶：適合的甘露聚糖酶包括細(xì)菌或真菌來源的那些。包括化學(xué)或基因修飾的突變體。甘露聚糖酶可以是家族5或26的堿性甘露聚糖酶。它可以是一種來自芽孢桿菌屬或腐質(zhì)霉屬的野生型，特別是粘瓊脂芽孢桿菌、地衣芽孢桿菌、耐鹽嗜堿芽孢桿菌(B.halodurans)、克勞氏芽孢桿菌(B.clausii)或特異腐質(zhì)霉。適合的甘露聚糖酶描述于WO1999/064619中。一種可商購的甘露聚糖酶是Mannaway(諾維信公司)。過氧化物酶/氧化酶：適合的過氧化物酶/氧化酶包括植物、細(xì)菌或真菌來源的那些。包括化學(xué)修飾的或蛋白質(zhì)工程化的突變體。有用的過氧化物酶的實(shí)例包括來自鬼傘屬，例如來自灰蓋鬼傘的過氧化物酶，及其變體，如在WO93/24618、WO95/10602、以及WO98/15257中描述的那些。可商購的過氧化物酶包括GuardzymeTM(諾維信公司)。蛋白酶：適合的蛋白酶包括細(xì)菌、真菌、植物、病毒或動物來源的那些，例如植物或微生物來源。優(yōu)選微生物來源。包括化學(xué)修飾的或蛋白質(zhì)工程化的突變體。它可以是一種堿性蛋白酶，例如絲氨酸蛋白酶或金屬蛋白酶。絲氨酸蛋白酶可以例如是S1家族(如胰蛋白酶)或S8家族(如枯草桿菌蛋白酶)。金屬蛋白酶可以例如是來自例如家族M4的嗜熱菌蛋白酶或其他金屬蛋白酶，例如來自M5、M7或M8家族的那些。術(shù)語“枯草桿菌酶”是指根據(jù)斯艾森(Siezen)等人，蛋白質(zhì)工程學(xué)(ProteinEngng.)4(1991)719-737和斯艾森等人，蛋白質(zhì)科學(xué)(ProteinScience)6(1997)501-523的絲氨酸蛋白酶亞組。絲氨酸蛋白酶是特征為在活性位點(diǎn)具有與底物形成共價加合物的絲氨酸的蛋白酶的一個亞組?？莶輻U菌酶可以劃分為6個亞部，即，枯草桿菌蛋白酶家族、嗜熱蛋白酶家族、蛋白酶K家族、羊毛硫抗生素肽酶家族、Kexin家族和Pyrolysin家族?？莶輻U菌酶的實(shí)例是來源于芽孢桿菌屬的那些，例如描述于US7262042和WO09/021867中的遲緩芽孢桿菌、嗜堿芽孢桿菌、枯草芽孢桿菌、解淀粉芽孢桿菌、短小芽孢桿菌和吉氏芽孢桿菌；和描述于WO89/06279中的枯草桿菌蛋白酶遲緩(lentus)、枯草桿菌蛋白酶諾和(Novo)、枯草桿菌蛋白酶嘉士伯(Carlsberg)、地衣芽孢桿菌、枯草桿菌蛋白酶BPN’、枯草桿菌蛋白酶309、枯草桿菌蛋白酶147和枯草桿菌蛋白酶168以及描述于(WO93/18140)中的蛋白酶PD138。其他有用的蛋白酶可以是描述于WO92/175177、WO01/016285、WO02/026024以及WO02/016547中的那些。胰蛋白酶樣蛋白酶的實(shí)例是胰蛋白酶(例如豬或牛來源的)和鐮孢菌蛋白酶(描述于WO89/06270、WO94/25583和WO05/040372中)，以及衍生自纖維單胞菌(Cellumonas)的胰凝乳蛋白酶(描述于WO05/052161和WO05/052146中)。進(jìn)一步優(yōu)選的蛋白酶是來自遲緩芽孢桿菌DSM5483的堿性蛋白酶(如在例如WO95/23221中所述)、及其變體(在WO92/21760、WO95/23221、EP1921147以及EP1921148中描述的)。金屬蛋白酶的實(shí)例是如描述于WO07/044993(杰能科國際公司(GenencorInt.))中的中性金屬蛋白酶，例如來源于解淀粉芽孢桿菌的那些。有用的蛋白酶的實(shí)例是于以下各項(xiàng)中的變體：WO92/19729、WO96/034946、WO98/20115、WO98/20116、WO99/011768、WO01/44452、WO03/006602、WO04/03186、WO04/041979、WO07/006305、WO11/036263、WO11/036264，尤其是在以下位置的一個或多個中具有取代的變體：3、4、9、15、27、36、57、68、76、87、95、96、97、98、99、100、101、102、103、104、106、118、120、123、128、129、130、160、167、170、194、195、199、205、206、217、218、222、224、232、235、236、245、248、252以及274，使用BPN’編號。更優(yōu)選地，這些枯草桿菌酶變體可以包含以下突變：S3T、V4I、S9R、A15T、K27R、*36D、V68A、N76D、N87S,R、*97E、A98S、S99G,D,A、S99AD、S101G,M,R、S103A、V104I,Y,N、S106A、G118V,R、H120D,N、N123S、S128L、P129Q、S130A、G160D、Y167A、R170S、A194P、G195E、V199M、V205I、L217D、N218D、M222S、A232V、K235L、Q236H、Q245R、N252K、T274A(使用BPN’編號)。適合的可商購蛋白酶包括以下列商品名出售的那些：DuralaseTm、DurazymTm、Ultra、Ultra、Ultra、Ultra、以及(諾維信公司)，以下列商品名出售的那些：PurafectPreferenzTm、PurafectPurafectPurafectEffectenzTm、以及(丹尼斯克/杜邦公司(Danisco/DuPont))、AxapemTM(吉斯特布羅卡德斯公司(Gist-BrocasesN.V.))、BLAP(序列示于US5352604的圖29中)及其變體(漢高股份(HenkelAG))以及來自花王株式會社(Kao)的KAP(嗜堿芽孢桿菌枯草桿菌蛋白酶)。脂肪酶和角質(zhì)酶：適合的脂肪酶和角質(zhì)酶包括細(xì)菌或真菌來源的那些。包括化學(xué)修飾的或蛋白質(zhì)工程化的突變體酶。實(shí)例包括來自嗜熱真菌屬的脂肪酶，例如如描述于EP258068和EP305216中的來自疏綿狀嗜熱絲孢菌(早先命名為疏棉狀腐質(zhì)霉)；來自腐質(zhì)霉屬的角質(zhì)酶，例如特異腐質(zhì)霉(WO96/13580)；來自假單胞菌屬的菌株的脂肪酶(這些中的一些現(xiàn)在改名為伯克霍爾氏菌屬)，例如產(chǎn)堿假單胞菌或類產(chǎn)堿假單胞菌(EP218272)、洋蔥假單胞菌(EP331376)、假單胞菌屬菌株SD705(WO95/06720&WO96/27002)、威斯康星假單胞菌(P.wisconsinensis)(WO96/12012)；GDSL-型鏈霉菌屬脂肪酶(WO10/065455)；來自稻瘟病菌的角質(zhì)酶(WO10/107560)；來自門多薩假單胞菌的角質(zhì)酶(US5,389,536)；來自褐色嗜熱裂孢菌(Thermobifidafusca)的脂肪酶(WO11/084412)；嗜熱脂肪土芽孢桿菌脂肪酶(WO11/084417)；來自枯草芽孢桿菌的脂肪酶(WO11/084599)；以及來自灰色鏈霉菌(WO11/150157)和始旋鏈霉菌(S.pristinaespiralis)的脂肪酶(WO12/137147)。其他實(shí)例是脂肪酶變體，例如描述于EP407225、WO92/05249、WO94/01541、WO94/25578、WO95/14783、WO95/30744、WO95/35381、WO95/22615、WO96/00292、WO97/04079、WO97/07202、WO00/34450、WO00/60063、WO01/92502、WO07/87508以及WO09/109500中的那些。優(yōu)選的商業(yè)化脂肪酶產(chǎn)品包括LipolaseTM、LipexTM；LipolexTM和LipocleanTM(諾維信公司)、Lumafast(來自杰能科公司(Genencor))以及Lipomax(來自吉斯特布羅卡德斯公司(Gist-Brocades))。再其他實(shí)例是有時稱為酰基轉(zhuǎn)移酶或過水解酶的脂肪酶，例如與南極假絲酵母(Candidaantarctica)脂肪酶A具有同源性的酰基轉(zhuǎn)移酶(WO10/111143)、來自恥垢分枝桿菌(Mycobacteriumsmegmatis)的酰基轉(zhuǎn)移酶(WO05/56782)、來自CE7家族的過水解酶(WO09/67279)以及恥垢分枝桿菌過水解酶的變體(特別是來自亨斯邁紡織品染化有限公司(HuntsmanTextileEffectsPteLtd)的商業(yè)產(chǎn)品GentlePowerBleach中所用的S54V變體)(WO10/100028)。淀粉酶：可以與本發(fā)明的酶一起使用的適合的淀粉酶可以是α-淀粉酶或葡糖淀粉酶并且可以具有細(xì)菌或真菌起源。包括化學(xué)修飾的或蛋白質(zhì)工程化的突變體。淀粉酶包括例如獲得自芽孢桿菌屬的α-淀粉酶，例如GB1,296,839中更詳細(xì)描述的地衣芽孢桿菌具體株系的α-淀粉酶。適合的淀粉酶包括具有WO95/10603中的SEQIDNO:2的淀粉酶或其與SEQIDNO:3具有90％序列一致性的變體。優(yōu)選的變體描述于WO94/02597、WO94/18314、WO97/43424以及WO99/019467的SEQIDNO:4中，例如在一個或多個以下位置中具有取代的變體：15、23、105、106、124、128、133、154、156、178、179、181、188、190、197、201、202、207、208、209、211、243、264、304、305、391、408以及444。不同的適合的淀粉酶包括具有WO02/010355中的SEQIDNO:6的淀粉酶或其與SEQIDNO:6具有90％序列一致性的變體。SEQIDNO:6的優(yōu)選變體是在位置181和182中具有缺失并且在位置193中具有取代的那些。其他適合的淀粉酶是包括示于WO2006/066594的SEQIDNO:6中的來源于解淀粉芽孢桿菌的α-淀粉酶的殘基1-33和示于WO2006/066594的SEQIDNO:4中的地衣芽孢桿菌α-淀粉酶的殘基36-483的雜合α-淀粉酶或其具有90％序列一致性的變體。這一雜合α-淀粉酶的優(yōu)選變體是在以下位置中的一個或多個中具有取代、缺失或插入的那些：G48、T49、G107、H156、A181、N190、M197、I201、A209以及Q264。包括示于WO2006/066594的SEQIDNO：6中的來源于解淀粉芽孢桿菌的α-淀粉酶的殘基1-33和SEQIDNO：4的殘基36-483的雜合α-淀粉酶的最優(yōu)選變體是具有以下取代的那些：M197T；H156Y+A181T+N190F+A209V+Q264S；或G48A+T49I+G107A+H156Y+A181T+N190F+I201F+A209V+Q264S。適合的另外的淀粉酶是具有WO99/019467中的SEQIDNO:6的淀粉酶或其與SEQIDNO:6具有90％序列一致性的變體。SEQIDNO:6的優(yōu)選變體是在以下位置中的一個或多個中具有取代、缺失或插入的那些：R181、G182、H183、G184、N195、I206、E212、E216以及K269。特別優(yōu)選的淀粉酶是在位置R181和G182或位置H183和G184中具有缺失的那些?？梢允褂玫牧硗獾牡矸勖甘蔷哂蠾O96/023873的SEQIDNO:1、SEQIDNO:3、SEQIDNO:2或SEQIDNO:7的那些或其與SEQIDNO:1、SEQIDNO:2、SEQIDNO:3或SEQIDNO:7具有90％序列一致性的變體。使用WO96/023873的SEQID2用于編號，SEQIDNO:1、SEQIDNO:2、SEQIDNO:3或SEQIDNO:7的優(yōu)選變體是在以下位置中的一個或多個中具有取代、缺失或插入的那些：140、181、182、183、184、195、206、212、243、260、269、304以及476。更優(yōu)選的變體是在選自181、182、183和184的兩個位置，例如181和182、182和183、或位置183和184具有缺失的那些。SEQIDNO:1、SEQIDNO:2或SEQIDNO:7的最優(yōu)選的淀粉酶變體是在位置183和184中具有缺失并且在位置140、195、206、243、260、304以及476的一個或多個中具有取代的那些?？梢允褂玫钠渌矸勖甘蔷哂蠾O08/153815中的SEQIDNO:2、WO01/66712中的SEQIDNO:10的淀粉酶或其與WO08/153815的SEQIDNO:2具有90％序列一致性或與WO01/66712中的SEQIDNO:10具有90％序列一致性的變體。WO01/66712中的SEQIDNO:10的優(yōu)選變體是在以下位置中的一個或多個中具有取代、缺失或插入的那些：176、177、178、179、190、201、207、211以及264。另外的適合的淀粉酶是具有WO09/061380中的SEQIDNO:2的淀粉酶或其與SEQIDNO:2具有90％序列一致性的變體。SEQIDNO:2的優(yōu)選變體是在以下位置中的一個或多個中具有C-末端的截短和/或取代、缺失或插入的那些：Q87、Q98、S125、N128、T131、T165、K178、R180、S181、T182、G183、M201、F202、N225、S243、N272、N282、Y305、R309、D319、Q320、Q359、K444以及G475。SEQIDNO:2的更優(yōu)選變體是在一個或多個以下位置中具有取代的那些：Q87E,R、Q98R、S125A、N128C、T131I、T165I、K178L、T182G、M201L、F202Y、N225E,R、N272E,R、S243Q,A,E,D、Y305R、R309A、Q320R、Q359E、K444E以及G475K和/或位置R180和/或S181或T182和/或G183的缺失。SEQIDNO:2的最優(yōu)選的淀粉酶變體是具有以下取代的那些：N128C+K178L+T182G+Y305R+G475K；N128C+K178L+T182G+F202Y+Y305R+D319T+G475K；S125A+N128C+K178L+T182G+Y305R+G475K；或S125A+N128C+T131I+T165I+K178L+T182G+Y305R+G475K，其中這些變體是C-末端截短的并且任選地進(jìn)一步在位置243處包括取代和/或在位置180和/或位置181處包括缺失。另外的適合的淀粉酶是具有WO13184577中的SEQIDNO:1的淀粉酶或其與SEQIDNO:1具有90％序列一致性的變體。SEQIDNO:1的優(yōu)選變體是在以下位置中的一個或多個中具有取代、缺失或插入的那些：K176、R178、G179、T180、G181、E187、N192、M199、I203、S241、R458、T459、D460、G476和G477。SEQIDNO:1的更優(yōu)選變體是以下位置：K176L、E187P、N192FYH、M199L、I203YF、S241QADN、R458N、T459S、D460T、G476K和G477K中的一個或多個中具有取代和/或在位置R179和/或S180或I181和/或G182中具有缺失的那些。SEQIDNO:1的最優(yōu)選的淀粉酶變體是具有以下取代的那些：E187P+I203Y+G476K，E187P+I203Y+R458N+T459S+D460T+G476K，其中這些變體任選地進(jìn)一步在位置241處包括取代和/或在位置178和/或位置179處包括缺失。另外的適合的淀粉酶是具有WO10104675中的SEQIDNO:1的淀粉酶或其與SEQIDNO:1具有90％序列一致性的變體。SEQIDNO:1的優(yōu)選變體是在以下位置中的一個或多個中具有取代、缺失或插入的那些：N21、D97、V128、K177、R179、S180、I181、G182、M200、L204、E242、G477和G478。SEQIDNO:1的更優(yōu)選變體是以下位置：N21D、D97N、V128I、K177L、M200L、L204YF、E242QA、G477K和G478K中的一個或多個中具有取代和/或在位置R179和/或S180或I181和/或G182中具有缺失的那些。SEQIDNO:1的最優(yōu)選的淀粉酶變體是具有以下取代的那些：N21D+D97N+V128I其中這些變體任選地進(jìn)一步在位置200處包括取代和/或在位置180和/或位置181處包括缺失。其他適合的淀粉酶是具有WO01/66712中的SEQIDNO:12的α-淀粉酶或與SEQIDNO:12具有至少90％序列一致性的變體。優(yōu)選的淀粉酶變體是在WO01/66712中的SEQIDNO:12的以下位置的一個或多個中具有取代、缺失或插入的那些：R28、R118、N174；R181、G182、D183、G184、G186、W189、N195、M202、Y298、N299、K302、S303、N306、R310、N314；R320、H324、E345、Y396、R400、W439、R444、N445、K446、Q449、R458、N471、N484。特別優(yōu)選的淀粉酶包括具有D183和G184的缺失并且具有R118K、N195F、R320K及R458K的取代的變體，以及另外在選自下組的一個或多個位置中具有取代的變體：M9、G149、G182、G186、M202、T257、Y295、N299、M323、E345以及A339，最優(yōu)選的是另外在所有這些位置中具有取代的變體。其他實(shí)例是例如描述于WO2011/098531、WO2013/001078及WO2013/001087中的那些淀粉酶變體?？缮藤彽牡矸勖甘荄uramylTM、特妙淀粉酶TM、FungamylTM、StainzymeTM、StainzymePlusTM、NatalaseTM、LiquozymeX及BANTM(來自諾維信公司)，以及RapidaseTM、PurastarTM/EffectenzTM、Powerase、PreferenzS1000、PreferenzS100及PreferenzS110(來自杰能科國際有限公司/杜邦公司(GenencorInternationalInc./DuPont))。該一種或多種洗滌劑酶可以通過添加包含一種或多種酶的單獨(dú)的添加劑，或通過添加包括所有這些酶的組合添加劑而被包括于洗滌劑組合物中。本發(fā)明的洗滌劑添加劑，即單獨(dú)的或組合的添加劑，可以配制成例如顆粒、液體、漿液等，優(yōu)選的洗滌劑添加劑劑型為顆粒，特別是無粉塵顆粒；液體，特別是穩(wěn)定化液體；或者漿液。非塵顆粒可以例如如在US4,106,991和4,661,452中所披露而產(chǎn)生，并且可以任選地通過本領(lǐng)域已知的方法進(jìn)行包衣。蠟狀包衣材料的實(shí)例為具有1000至20000的平均摩爾重量的聚(環(huán)氧乙烷)產(chǎn)物(聚乙二醇，PEG)；具有從16至50個環(huán)氧乙烷單元的乙氧化壬基苯酚；乙氧化脂肪醇，其中該醇包含從12至20個碳原子，并且其中具有15至80個環(huán)氧乙烷單元；脂肪醇；脂肪酸；以及脂肪酸的甘油單酯和甘油二酯以及甘油三酯。適用于通過流化床技術(shù)應(yīng)用的成膜包衣材料的實(shí)例在GB1483591中給出。液體酶制品可以例如通過根據(jù)已確立的方法添加多元醇(如丙二醇)、糖或糖醇、乳酸或硼酸而穩(wěn)定化。受保護(hù)的酶可以根據(jù)EP238,216中披露的方法來制備。輔料還可以利用本領(lǐng)域中已知的用于在衣物洗滌劑中使用的任何洗滌劑組分。其他任選的洗滌劑組分包括防腐劑、防縮劑、抗污垢再沉積劑、抗皺劑、殺細(xì)菌劑、粘合劑、腐蝕抑制劑、崩解劑(disintegrant)/崩解試劑(disintegrationagent)、染料、酶穩(wěn)定劑(包括硼酸、硼酸鹽、CMC和/或多元醇如丙二醇)、織物整理劑(包括粘土)、填充劑/加工助劑、熒光增白劑/光學(xué)增亮劑、增泡劑、泡沫(泡)調(diào)節(jié)劑、香料、污垢助懸劑、軟化劑、抑泡劑、晦暗抑制劑以及芯吸劑，單獨(dú)或組合使用?？梢岳帽绢I(lǐng)域中已知的用于在衣物洗滌劑中使用的任何成分。此類成分的選擇完全在普通技術(shù)人員的技術(shù)范圍內(nèi)。分散劑：本發(fā)明的洗滌劑組合物還可以包含分散劑。具體地說，粉末洗滌劑可以包括分散劑。適合的水溶性有機(jī)材料包括均聚合或共聚合的酸或其鹽，其中聚羧酸包括至少兩個羧基，這兩個羧基被不超過兩個碳原子彼此分開。適合的分散劑例如描述于粉末洗滌劑，表面活性劑科學(xué)系列(SurfactantScienceSeries)，第71卷中，馬塞爾·德克爾公司(MarcelDekker)。染料轉(zhuǎn)移抑制劑：本發(fā)明的洗滌劑組合物還可以包括一種或多種染料轉(zhuǎn)移抑制劑。適合的聚合物染料轉(zhuǎn)移抑制劑包括但不限于聚乙烯吡咯烷酮聚合物、多胺N-氧化物聚合物、N-乙烯吡咯烷酮與N-乙烯基咪唑的共聚物、聚乙烯噁唑烷酮以及聚乙烯咪唑或其混合物。當(dāng)存在于主題組合物中時，染料轉(zhuǎn)移抑制劑可以按組合物重量計(jì)的以下水平存在：從約0.0001％至約10％、從約0.01％至約5％或甚至從約0.1％至約3％。熒光增白劑：本發(fā)明的洗滌劑組合物還可以優(yōu)選地包含另外的組分，這些組分可以給正清潔的物品著色，例如熒光增白劑或光學(xué)增亮劑。其中增亮劑優(yōu)選以約0.01％至約0.5％的水平存在。在本發(fā)明的組合物中可以使用適合用于在衣物洗滌劑組合物中使用的任何熒光增白劑。最常用的熒光增白劑是屬于以下類別的那些：二氨芪-磺酸衍生物、二芳基吡唑啉衍生物和二苯基-聯(lián)苯乙烯基衍生物。熒光增白劑的二氨芪-磺酸衍生物型的實(shí)例包括以下各項(xiàng)的鈉鹽：4,4'-雙-(2-二乙醇氨基-4-苯胺基-s-三嗪-6-基氨基)芪-2,2'-二磺酸鹽；4,4'-雙-(2,4-二苯胺基-s-三嗪-6-基氨基)芪-2.2'-二磺酸鹽；4,4'-雙-(2-苯胺基-4(N-甲基-N-2-羥基-乙氨基)-s-三嗪-6-基氨基)芪-2,2'-二磺酸鹽，4,4'-雙-(4-苯基-2,1,3-三唑-2-基)芪-2,2'-二磺酸鹽；4,4'-雙-(2-苯胺基-4(1-甲基-2-羥基-乙氨基)-s-三嗪-6-基氨基)芪-2,2'-二磺酸鹽和2-(二苯乙烯基-4"-萘-1.,2':4,5)-1,2,3-三唑-2"-磺酸鹽。優(yōu)選的熒光增白劑是可從汽巴-嘉基股份有限公司(Ciba-GeigyAG)(巴塞爾，瑞士)獲得的天來寶(Tinopal)DMS和天來寶CBS。天來寶DMS是4,4'-雙-(2-嗎啉基-4苯胺基-s-三嗪-6-基氨基)芪二磺酸鹽的二鈉鹽。天來寶CBS是2,2'-雙-(苯基-苯乙烯基)二磺酸鹽的二鈉鹽。還優(yōu)選熒光增白劑，是可商購的ParawhiteKX，由派拉蒙礦物與化學(xué)(ParamountMineralsandChemicals)，孟買，印度供應(yīng)。適合用于在本發(fā)明中使用的其他熒光劑包括1-3-二芳基吡唑啉和7-烷氨基香豆素。適合的熒光增亮劑水平包括從約0.01wt％、從0.05wt％、從約0.1wt％或甚至從約0.2wt％的較低水平至0.5wt％或甚至0.75wt％的較高水平。污垢釋放聚合物：本發(fā)明的洗滌劑組合物還可以包括一種或多種污垢釋放聚合物，這些污垢釋放聚合物幫助從織物，例如棉或聚酯基織物上除去污垢，特別是從聚酯基織物上除去疏水污垢。污垢釋放聚合物可以例如是非離子型或陰離子型對苯二甲酸基聚合物、聚乙烯基己內(nèi)酰胺和相關(guān)共聚物、乙烯基接枝共聚物、聚酯聚酰胺，參見例如粉末洗滌劑，表面活性劑科學(xué)系列第71卷第7章，馬塞爾·德克爾公司(MarcelDekker，Inc.)。另一種類型的污垢釋放聚合物是包括核心結(jié)構(gòu)和連接至該核心結(jié)構(gòu)的多個烷氧基化基團(tuán)的兩親性烷氧基化油污清潔聚合物。核心結(jié)構(gòu)可以包括聚烷基亞胺結(jié)構(gòu)或聚烷醇胺結(jié)構(gòu)，如WO2009/087523中詳細(xì)描述的(將其通過引用而特此結(jié)合)。此外，任意接枝共聚物是適合的污物釋放聚合物。適合的接枝共聚物更詳細(xì)地描述于WO2007/138054、WO2006/108856以及WO2006/113314中(將其通過引用而特此結(jié)合)。其他污垢釋放聚合物是取代的多糖結(jié)構(gòu)，尤其是取代的纖維素結(jié)構(gòu)，例如改性纖維素衍生物，例如EP1867808或WO2003/040279中描述的那些(將二者都通過引用而特此結(jié)合)。適合的纖維素聚合物包括纖維素、纖維素醚、纖維素酯、纖維素酰胺及其混合物。適合的纖維素聚合物包括陰離子改性的纖維素、非離子改性的纖維素、陽離子改性的纖維素、兼性離子改性的纖維素及其混合物。適合的纖維素聚合物包括甲基纖維素、羧甲基纖維素、乙基纖維素、羥乙基纖維素、羥丙基甲基纖維素、酯羧甲基纖維素及其混合物。抗再沉積劑：本發(fā)明的洗滌劑組合物還可以包括一種或多種抗再沉積劑，例如羧甲基纖維素(CMC)、聚乙烯醇(PVA)、聚乙烯吡咯烷酮(PVP)、聚環(huán)氧乙烷和/或聚乙二醇(PEG)、丙烯酸的均聚物、丙烯酸與馬來酸的共聚物以及乙氧基化聚乙亞胺。以上在污垢釋放聚合物下描述的纖維素基聚合物還可以用作抗再沉積劑。其他適合的輔料包括但不限于防縮劑、抗皺劑、殺細(xì)菌劑、粘合劑、載體、染料、酶穩(wěn)定劑、織物柔軟劑、填充劑、泡沫調(diào)節(jié)劑、助水溶劑、香料、色素、抑泡劑、溶劑以及用于液體洗滌劑的結(jié)構(gòu)劑和/或結(jié)構(gòu)彈性劑。洗滌劑產(chǎn)品的配制本發(fā)明的洗滌劑組合物可以處于任何常規(guī)形式，例如條、均勻的片劑、具有兩個或更多個層的片劑、具有一個或多個室的袋、規(guī)則的或壓縮的粉末、顆粒、膏、凝膠、或規(guī)則的、壓縮的或濃縮的液體。存在多種洗滌劑配制品形式，例如層(相同或不同相)、袋以及用于機(jī)械給料裝置的形式?？梢詫⑿〈渲脼閱我桓羰一蚨喔羰?。它可以具有適合保存該組合物的任何形式、形狀和材料，例如在與水接觸之前，不允許該組合物從袋中釋放出來。袋由封裝內(nèi)體積的水溶性膜制成。可以將所述內(nèi)體積分為袋的室。優(yōu)選的膜是形成膜或片的聚合材料，優(yōu)選是聚合物。優(yōu)選的聚合物、共聚物或其衍生物選自聚丙烯酸酯、和水溶性丙烯酸酯共聚物、甲基纖維素、羧甲基纖維素、糊精鈉、乙基纖維素、羥乙基纖維素、羥丙基甲基纖維素、麥芽糊精、聚甲基丙烯酸酯，最優(yōu)選地是聚乙烯醇共聚物和羥丙基甲基纖維素(HPMC)。優(yōu)選地，在膜中的聚合物(例如PVA)的水平是至少約60％。優(yōu)選的平均分子量將典型地是約20,000至約150,000。膜還可以是共混物組合物，該共混物組合物包括可水解降解并且水可溶的聚合物共混物，例如聚乳酸和聚乙烯醇(已知在貿(mào)易參考M8630下，如由美國印第安納州蓋里(Gary,Ind.，US)的克里斯克拉夫特工業(yè)產(chǎn)品公司(ChrisCraftIn.Prod.)銷售)加增塑劑，像甘油、乙二醇、丙二醇、山梨醇及其混合物。這些袋可以包括固體衣物清潔組合物或部分組分和/或液體清潔組合物或由水溶性膜分開的部分組分。用于液體組分的室在組成上可以與包括固體的室不同(US2009/0011970A1)?？梢杂伤扇艿拇谢蚱瑒┑牟煌瑢又械氖襾韺⑾礈靹┏煞治锢淼乇舜朔珠_。由此可以避免組分之間的負(fù)面的存儲相互作用。在洗滌溶液中，每個室的不同溶解曲線還可以引起選擇的組分的延遲溶解。非單位劑量的液體或凝膠洗滌劑可以是水性的，典型地包含按重量計(jì)至少20％并且最高達(dá)95％的水，例如高達(dá)約70％的水、高達(dá)約65％的水、高達(dá)約55％的水、高達(dá)約45％的水、高達(dá)約35％的水。包括但不限于鏈烷醇、胺、二醇、醚以及多元醇的其他類型的液體可以被包括在水性液體或凝膠中。含水液體或凝膠洗滌劑可以包含從0-30％的有機(jī)溶劑。液體或凝膠洗滌劑可以是非水性的。洗衣皂?xiàng)l本發(fā)明的酶可以被添加至洗衣皂?xiàng)l中并且用于手洗洗衣、織物和/或紡織品。術(shù)語洗衣皂?xiàng)l包括洗衣條、皂?xiàng)l、組合條(combobar)、合成洗滌劑條以及洗滌劑條。條的類型通常區(qū)別在于它們包含的表面活性劑的類型，并且術(shù)語洗滌皂?xiàng)l包括包含來自脂肪酸的皂和/或合成皂的那些。洗滌皂?xiàng)l具有在室溫下為固體而非液體、凝膠或粉末的物理形式。術(shù)語固體被定義為不隨著時間顯著變化的物理形式，即如果將固體物體(例如洗衣皂?xiàng)l)放置于容器內(nèi)部，該固體物體不發(fā)生改變來填充它被放置于其中的容器。該條是典型地呈條形式但是可以呈其他固體形狀、如圓形或卵形的一種固體。洗衣皂?xiàng)l可以包括一種或多種另外的酶，蛋白酶抑制劑例如肽醛類(或次硫酸鹽加合物或半縮醛加合物)，硼酸，硼酸鹽，硼砂和/或苯基硼酸衍生物例如4-甲酰基苯基硼酸，一種或多種肥皂或合成表面活性劑，多元醇例如甘油，pH控制化合物例如脂肪酸、檸檬酸、乙酸和/或甲酸，和/或一價陽離子和有機(jī)陰離子的鹽，其中該一價陽離子可以是例如Na+、K+或NH4+并且該有機(jī)陰離子可以是例如甲酸鹽、乙酸鹽、檸檬酸鹽或乳酸鹽，這樣使得一價陽離子和有機(jī)陰離子的鹽可以是例如甲酸鈉。洗衣皂?xiàng)l還可以包括絡(luò)合劑像EDTA和HEDP，香料和/或不同類型的填充劑，表面活性劑例如陰離子型合成表面活性劑，助洗劑，聚合的污物釋放劑，洗滌劑螯合劑，穩(wěn)定劑，填充劑，染料，著色劑，染料轉(zhuǎn)移抑制劑，烷氧基化的聚碳酸酯，抑泡劑，結(jié)構(gòu)劑，粘合劑，浸出劑，漂白活化劑，粘土去污劑，抗再沉積劑，聚合分散劑，增白劑，織物柔軟劑，香料和/或本領(lǐng)域已知的其他化合物。洗衣皂?xiàng)l可以在常規(guī)的洗衣皂?xiàng)l制造設(shè)備中進(jìn)行加工，例如但不限制于：混合器、壓條機(jī)例如雙級真空壓條機(jī)、擠出機(jī)、切割機(jī)、標(biāo)識壓模機(jī)(logo-stamper)、冷卻隧道以及包裝機(jī)。本發(fā)明不局限于通過任何單一方法制備洗衣皂?xiàng)l?？梢栽谶^程的不同階段向肥皂中添加本發(fā)明的預(yù)混料。例如，可以制備包含肥皂、酶、任選地一種或多種另外的酶、蛋白酶抑制劑以及一價陽離子和有機(jī)陰離子的鹽的預(yù)混料并且然后將該混合物壓條。可以同時添加作為例如處于液態(tài)的蛋白酶抑制劑的酶以及任選的另外的酶。除了混合步驟和壓條步驟以外，該工藝還可以進(jìn)一步包括研磨、擠出、切割、壓模、冷卻和/或包裝的步驟。顆粒洗滌劑配制品如描述于WO09/092699、EP1705241、EP1382668、WO07/001262、US6472364、WO04/074419或WO09/102854中的，可以配制顆粒洗滌劑。其他有用的洗滌劑配制品描述于WO09/124162、WO09/124163、WO09/117340、WO09/117341、WO09/117342、WO09/072069、WO09/063355、WO09/132870、WO09/121757、WO09/112296、WO09/112298、WO09/103822、WO09/087033、WO09/050026、WO09/047125、WO09/047126、WO09/047127、WO09/047128、WO09/021784、WO09/010375、WO09/000605、WO09/122125、WO09/095645、WO09/040544、WO09/040545、WO09/024780、WO09/004295、WO09/004294、WO09/121725、WO09/115391、WO09/115392、WO09/074398、WO09/074403、WO09/068501、WO09/065770、WO09/021813、WO09/030632和WO09/015951、WO2011025615、WO2011016958、WO2011005803、WO2011005623、WO2011005730、WO2011005844、WO2011005904、WO2011005630、WO2011005830、WO2011005912、WO2011005905、WO2011005910、WO2011005813、WO2010135238、WO2010120863、WO2010108002、WO2010111365、WO2010108000、WO2010107635、WO2010090915、WO2010033976、WO2010033746、WO2010033747、WO2010033897、WO2010033979、WO2010030540、WO2010030541、WO2010030539、WO2010024467、WO2010024469、WO2010024470、WO2010025161、WO2010014395、WO2010044905、WO2010145887、WO2010142503、WO2010122051、WO2010102861、WO2010099997、WO2010084039、WO2010076292、WO2010069742、WO2010069718、WO2010069957、WO2010057784、WO2010054986、WO2010018043、WO2010003783、WO2010003792、WO2011023716、WO2010142539、WO2010118959、WO2010115813、WO2010105942、WO2010105961、WO2010105962、WO2010094356、WO2010084203、WO2010078979、WO2010072456、WO2010069905、WO2010076165、WO2010072603、WO2010066486、WO2010066631、WO2010066632、WO2010063689、WO2010060821、WO2010049187、WO2010031607、WO2010000636中。產(chǎn)生組合物的方法本發(fā)明還涉及產(chǎn)生組合物的方法。該方法可以與洗滌劑組合物的(存儲)穩(wěn)定性相關(guān)：例如，肥皂?xiàng)l預(yù)混方法WO2009155557。用途本發(fā)明針對用于使用α-淀粉酶變體或其組合物在清潔過程例如衣物洗滌或包括自動化餐具洗滌的硬表面清潔中的方法。對于清潔而言重要的污物和污漬由許多不同物質(zhì)構(gòu)成，并且已經(jīng)開發(fā)全都具有不同底物特異性的一系列不同的酶用于在涉及衣物和硬表面清潔(例如餐具洗滌)兩者中使用。這些酶被認(rèn)為提供酶洗滌益處，因?yàn)榕c不具有酶的同一過程相比，它們在其應(yīng)用的清潔過程中特異性地改進(jìn)污漬去除。本領(lǐng)域已知的去污酶包括以下酶，例如蛋白酶、淀粉酶、脂肪酶、角質(zhì)酶、纖維素酶、內(nèi)切葡聚糖酶、木葡聚糖酶、果膠酶、果膠裂解酶、黃原膠酶、過氧化物酶、鹵代過氧酶、過氧化氫酶以及甘露聚糖酶。在一個方面中，本發(fā)明涉及本發(fā)明的α-淀粉酶變體在洗滌劑組合物中用于在清潔硬表面中使用(例如餐具洗滌)，或在洗衣中或用于去污的用途。本發(fā)明的另一個方面是在洗滌劑組合物中和在洗滌劑應(yīng)用中使用包括本發(fā)明的α-淀粉酶連同一種或多種表面活性劑以及任選地一種或多種選自以下清單的洗滌劑組分的洗滌劑組合物，該清單包括助水溶劑、助洗劑和共助洗劑、漂白系統(tǒng)、聚合物、織物調(diào)色劑和輔料或其任何混合物。一個另外的方面是在洗滌劑組合物或洗滌劑應(yīng)用中使用包括本發(fā)明的α-淀粉酶連同一種或多種表面活性劑以及一種或多種選自下組的另外的酶的洗滌劑組合物，該組包括蛋白酶、脂肪酶、角質(zhì)酶、纖維素酶、內(nèi)切葡聚糖酶、木葡聚糖酶、果膠酶、果膠裂解酶、黃原膠酶、過氧化物酶、鹵代過氧酶、過氧化氫酶以及甘露聚糖酶或其任何混合物。在另一個方面，本發(fā)明涉及洗衣方法，該方法可用于家用洗衣以及工業(yè)洗衣。此外，本發(fā)明涉及用于洗滌紡織品(例如織物、服裝(garment)、衣服(cloth)等)的方法，其中該方法包括用洗滌溶液處理該紡織品，該洗滌溶液包含洗滌劑組合物以及本發(fā)明的α-淀粉酶。例如可以使用家用或工業(yè)洗衣機(jī)進(jìn)行洗衣或可以使用洗滌劑組合物手動地進(jìn)行洗衣，該洗滌劑組合物包含本發(fā)明的α-淀粉酶變體。在另一個方面，本發(fā)明涉及餐具洗滌方法，該方法可用于家用餐具洗滌以及工業(yè)餐具洗滌。此外，本發(fā)明涉及用于洗滌硬表面(例如，用餐工具，如刀、叉、匙；陶器，如盤子、玻璃杯、碗；以及平底鍋)的方法，其中該方法包括用洗滌溶液處理該硬表面，該洗滌溶液包含洗滌劑組合物和本發(fā)明的變體?？梢岳缡褂眉矣没蚬I(yè)洗碗機(jī)洗滌硬表面或使用洗滌劑組合物手動地洗滌硬表面，該洗滌劑組合物包含本發(fā)明的α-淀粉酶、任選地連同一種或多種選自下組的另外的酶，該組包括：蛋白酶、淀粉酶、脂肪酶、角質(zhì)酶、纖維素酶、內(nèi)切葡聚糖酶、木葡聚糖酶、果膠酶、果膠裂解酶、黃原膠酶、過氧化物酶、鹵代過氧酶、過氧化氫酶、甘露聚糖酶、或其任何混合物。在又一方面，本發(fā)明涉及用于從表面去除污漬的方法，該方法包括使該表面與在洗滌劑組合物中和在洗滌劑應(yīng)用中的包括本發(fā)明的α-淀粉酶連同一種或多種表面活性劑以及任選地一種或多種選自以下清單的洗滌劑組分的組合物接觸，該清單包括助水溶劑、助洗劑和共助洗劑、漂白系統(tǒng)、聚合物、織物調(diào)色劑和輔料或其任何混合物。一個另外的方面是一種用于從表面去除污漬的方法，該方法包括使該表面與在洗滌劑組合物中和在洗滌劑應(yīng)用中包括本發(fā)明的α-淀粉酶變體連同一種或多種表面活性劑、一種或多種選自下組的另外的酶的組合物接觸，該組包括蛋白酶、脂肪酶、角質(zhì)酶、纖維素酶、內(nèi)切葡聚糖酶、木葡聚糖酶、果膠酶、果膠裂解酶、黃原膠酶、過氧化物酶、鹵代過氧酶、過氧化氫酶、甘露聚糖酶或其任何混合物。實(shí)例淀粉酶表達(dá)：本發(fā)明的α-淀粉酶變體可以通過文獻(xiàn)中熟知的方法進(jìn)行表達(dá)，這些方法典型地包括將編碼淀粉酶的基因轉(zhuǎn)化到芽孢桿菌屬菌株(如枯草芽孢桿菌)中并使該生物體在搖瓶中生長。詳情描述于以下。菌株：例如，枯草芽孢桿菌或地衣芽孢桿菌，這些菌株在質(zhì)粒上的或整合在芽孢桿菌屬染色體上(例如在Pel或Amy基因座中)的表達(dá)盒中攜帶淀粉酶。淀粉酶表達(dá)：將包含本發(fā)明的α-淀粉酶變體基因的芽孢桿菌屬生物體接種在含有氯霉素(8μg/ml)的LB肉湯中并在37℃下生長過夜。針對α-淀粉酶的表達(dá)，將1％-2％的過夜培養(yǎng)物加入到1000ml帶擋板的燒瓶中的300ml的GBT-16培養(yǎng)基中，并在37℃下生長72h。培養(yǎng)基：GBT-16將pH調(diào)節(jié)至pH7并將培養(yǎng)基進(jìn)行高壓殺菌。就在接種前分開高壓殺菌并且添加實(shí)例1：變體的構(gòu)建使用由在Pel基因座處含有LASB0000(SEQIDNO:6)基因或SEQIDNO:3的基因的菌株制備的基因組DNA作為用于產(chǎn)生定點(diǎn)突變體的模板。使用誘變正向引物和PnMi4490(CAATCCAAGAGAACCCTGATACGGATG-SEQIDNO:17)反向引物產(chǎn)生約3.8kb片段。該片段與PnMi4491(CGGAACGCCTGGCTGACAACACG-SEQIDNO:18)正向引物一起用作大引物，得到6kb插入盒。為了通過轉(zhuǎn)化時的雙交換實(shí)現(xiàn)在Pel基因座中的整合，連同LASB0000(SEQIDNO:6)和cat基因，該盒在末端包含上游和下游Pel序列。為了組合在線性氨基酸序列(例如，變體1：G50A+A51T+R172D+N195F+I206Y，和變體2：N195F+I206Y+E345D+E346P+D476G)中良好分離的突變，進(jìn)行通過重疊延伸的拼接(SOE)PCR。使用內(nèi)部引物(Assemb19：TGGGGTGTTTGGTACACAAACAC正向(SEQIDNO:19)和Assemb20：CCAATCGCGCGTAAAGCTATAC反向(SEQIDNO:20))分別與PnMi4490或PnMi4491產(chǎn)生針對SOEPCR的兩個重疊的DNA片段。例如，PnMi4491和Assemb20用于變體1，而Assemb19和PnMi4490用于變體2。在含有氯霉素的LB瓊脂上進(jìn)行選擇，并且通過淀粉酶基因的DNA測序確認(rèn)突變。在三聯(lián)啟動子系統(tǒng)(如WO99/43835中所述)下表達(dá)淀粉酶基因，該三聯(lián)啟動子系統(tǒng)由來自地衣芽孢桿菌α-淀粉酶基因(amyL)、解淀粉芽孢桿菌α-淀粉酶基因(amyQ)、和蘇云金芽孢桿菌cryIIIA啟動子(包括控制淀粉酶表達(dá)的穩(wěn)定化序列)的啟動子組成；以及用以指導(dǎo)到細(xì)胞外的輸出的地衣芽孢桿菌淀粉酶信號的信號序列。淀粉酶的純化：將該發(fā)酵液在13131g下離心25分鐘，以去除細(xì)胞塊，并且然后使用0.7微米的玻璃濾器GF-F(沃特曼(Whatman))使用tarsons過濾組件進(jìn)行過濾。通過兩步方案進(jìn)行淀粉酶的純化，即疏水相互作用層析(HIC)，然后是凝膠過濾。將含有1M硫酸銨的肉湯加載到20ml含有來自伯樂公司(Biorad)的甲基HIC支持物的柱上，該柱用平衡緩沖液(含有1M硫酸銨、1mM氯化鈣的50mMHEPESpH8)進(jìn)行預(yù)平衡。加載該肉湯后，用洗滌緩沖液(含有0.85M硫酸銨、1mM氯化鈣的50mMHEPESpH8)洗滌柱子，并且用洗脫緩沖液(50mMHEPESpH8，1mM氯化鈣)進(jìn)行洗脫。合并含有淀粉酶蛋白質(zhì)的級分，并傳遞到用含有50mMHEPESpH8和1mM氯化鈣的緩沖液預(yù)平衡的SephadexG25(西格瑪(Sigma))柱(200ml柱體積)上。實(shí)例2-α-淀粉酶活性的測定PNP-G7測定可以通過使用G7-pNP底物的方法確定α-淀粉酶活性?？s寫為4,6-亞乙基(G7)-對硝基苯基(G1)-α,D-麥芽庚糖苷的G7-pNP是一種可以由內(nèi)切淀粉酶如α-淀粉酶切割的嵌段寡糖。切割之后，試劑盒中所包括的α-葡糖苷酶進(jìn)一步消化水解底物以釋放自由PNP分子，該分子具有黃顏色并且因而可通過可見分光光度法在λ＝405nm(400-420nm)處測量。含有G7-pNP底物和α-葡糖苷酶的試劑盒由羅氏/日立公司(Roche/Hitachi)制造(目錄號11876473)。試劑：來自這個試劑盒的G7-pNP底物含有22mM4,6-亞乙基-G7-pNP和52.4mMHEPES(2-[4-(2-羥乙基)-1-哌嗪基]-乙磺酸)，pH7.0。α-葡糖苷酶試劑含有52.4mMHEPES、87mMNaCl、12.6mMMgCl2、0.075mMCaCl2、>4kU/L的α-葡糖苷酶。通過將1mLα-葡糖苷酶試劑與0.2mLG7-pNP底物混合，產(chǎn)生底物工作溶液。此底物工作溶液在使用之前立即制成。稀釋緩沖液：50mMMOPS，0.05％(w/v)TritonX100(聚乙二醇對-(1,1,3,3-四甲基丁基)-苯基醚(C14H22O(C2H4O)n(n＝9-10)))，1mMCaCl2，pH8.0。程序：將有待分析的淀粉酶樣品稀釋于稀釋緩沖液中以確保稀釋樣品中的pH是7。通過將20μl稀釋酶樣品轉(zhuǎn)移至96孔微量滴定板并且添加80μl底物工作溶液來執(zhí)行測定。將溶液混合并且在室溫下預(yù)孵育1分鐘并且在OD405nm下在5分鐘內(nèi)每20秒測量吸收。在一組給定條件下，時間相關(guān)吸收曲線的斜率(每分鐘的吸光度)與所討論的α-淀粉酶的比活性(活性/mg酶)成正比例。淀粉酶樣品應(yīng)稀釋至其中斜率低于0.4吸光度單位/分鐘的水平。Phadebas活性測定：α-淀粉酶活性還可通過使用Phadebas底物(例如來自麥戈?duì)柹茖W(xué)(MagleLifeSciences)，隆德(Lund)，瑞典(Sweden))的方法來確定。Phadebas片劑包括互聯(lián)淀粉聚合物，這些聚合物呈不溶于水的球狀微球形式。將一種藍(lán)色染料共價結(jié)合至這些微球。微球中的互聯(lián)淀粉聚合物以與α-淀粉酶活性成比例的速度降解。當(dāng)α-淀粉酶降解了淀粉聚合物時，釋放的藍(lán)色染料是可溶于水的并且染料濃度可通過在620nm下測量吸光度來確定。藍(lán)色的濃度與樣品中的α-淀粉酶活性成比例。將有待分析的淀粉酶樣品稀釋于具有所需pH的活性緩沖液中。將一個底物片劑懸浮于5mL活性緩沖液中并且在磁力攪拌器上混合。在混合底物期間，將150μl轉(zhuǎn)移至微量滴定板(MTP)或PCR-MTP。將30μl稀釋淀粉酶樣品添加至150μl底物并且混合。37℃下孵育15分鐘。通過添加30μl1MNaOH并且混合來停止反應(yīng)。在4000xg下離心MTP5分鐘。將100μl轉(zhuǎn)移至新MTP并且測量620nm下的吸光度。淀粉酶樣品應(yīng)稀釋成使得620nm下的吸光度在0與2.2之間，并且在活性測定的線性范圍內(nèi)。還原糖活性測定：α-淀粉酶活性還可以通過使用例如玉米淀粉底物的還原糖測定來確定。通過與p-羥基苯甲酸酰肼(PHBAH)反應(yīng)來確定用α-淀粉酶水解淀粉中的α-1,4-糖苷鍵所形成的多個還原端。與PHBAH反應(yīng)之后，可通過405nm下的吸光度來測量還原端的數(shù)量并且還原端的濃度與樣品中的α-淀粉酶活性成比例。使玉米淀粉底物(3mg/mL)在milliQ水中蒸煮5分鐘來溶解并且在測定之前冷卻。關(guān)于終止液，制備Ka-Na-酒石酸鹽/NaOH溶液(K-Na-酒石酸鹽(默克(Merck)8087)50g/l，NaOH20g/l)并且通過將對-羥基苯甲酸酰肼(PHBAH，西格瑪(Sigma)H9882)添加至Ka-Na-酒石酸鹽/NaOH溶液至15mg/mL來新鮮制備終止液。在PCR-MTP中，將50μl活性緩沖液與50μl底物混合。添加50μl稀釋酶并且混合。在PCR機(jī)器中在所需溫度孵育5分鐘。通過添加75μl終止液(Ka-Na-酒石酸鹽/NaOH/PHBAH)來停止反應(yīng)。在PCR機(jī)器中在95℃孵育10分鐘。將150μl轉(zhuǎn)移至新MTP并且測量405nm下的吸光度。淀粉酶樣品應(yīng)稀釋成使得405nm下的吸光度在0與2.2之間，并且在活性測定的線性范圍內(nèi)。測定：為了確定殘余淀粉酶活性，可以使用Ultra淀粉酶測定試劑盒(E33651，英杰公司(Invitrogen)，拉霍亞(LaJolla)，加州(CA)，美國(USA))。底物是玉米淀粉衍生物，DQTM淀粉，它是用FL染料標(biāo)記以使得熒光被淬滅的玉米淀粉。含有大約1mg凍干底物的一個小瓶溶解于100微升50mM乙酸鈉(pH4.0)中。將小瓶渦旋20秒并且在室溫下、黑暗中保持，并偶爾混合直到溶解為止。然后添加900微升100mM乙酸鹽、0.01％(w/v)X100、0.125mMCaCl2，pH5.5，充分渦旋并且在室溫下、黑暗中儲存直到準(zhǔn)備使用為止。通過以10倍稀釋于殘余活性緩沖液(100mM乙酸鹽、0.01％(w/v)X100、0.125mMCaCl2，pH5.5)中來制備儲備底物工作溶液。孵育之后立即將酶在100mM乙酸鹽、0.01％(W/v)X100、0.125mMCaCl2，pH5.5中稀釋至10-20ng酶蛋白/ml的濃度。為了測定，在黑色384孔微量滴定板中，將25微升底物工作溶液與25微升稀釋酶混合10秒。在每個孔中在25℃于15分鐘內(nèi)每分鐘測量熒光強(qiáng)度(激發(fā)：485nm，發(fā)射：555nm)并且將Vmax計(jì)算作為熒光強(qiáng)度相對于時間的曲線的斜率。曲線應(yīng)是線性的，并且調(diào)整了殘余活性測定以使得稀釋的參照酶溶液在活性測定的線性范圍內(nèi)。參照α-淀粉酶該參照α-淀粉酶可以是SEQIDNO:2的淀粉酶。如果沒有另外說明，則使用pNP-G7測定用于確定這些變體的α淀粉酶活性。實(shí)例3-使用自動機(jī)械應(yīng)力測定的α-淀粉酶的洗滌性能(AMSA)為了評定α-淀粉酶在洗滌劑基礎(chǔ)組合物中的洗滌性能，可以使用自動機(jī)械應(yīng)力測定(AMSA)進(jìn)行洗滌實(shí)驗(yàn)。使用AMSA測試，可以檢査大量小體積酶洗滌劑溶液的洗滌性能。AMSA板具有許多用于測試溶液的縫和蓋子，蓋子將待洗滌的紡織品小塊布樣對所有縫開口強(qiáng)力擠壓。在洗滌時間期間，板、測試溶液、紡織品和蓋子劇烈振動從而使測試溶液與紡織品接觸并以規(guī)則、周期性擺動方式施加機(jī)械應(yīng)力。關(guān)于進(jìn)一步描述，參見WO02/42740，尤其是第23-24頁的“具體方法實(shí)施例”段落。洗滌性能總體描述制備測試溶液，該測試溶液包含水(6°dH)、0.79g/l洗滌劑(例如，如下文描述的標(biāo)準(zhǔn)洗滌劑J)和處于濃度0或0.05mg或0.2mg酶蛋白/L的本發(fā)明的酶。添加帶有淀粉污漬的織物(來自測試材料中心BV的CS-28，郵箱120，3133KT，弗拉爾丁恩，荷蘭)并且將它們在15℃和30℃洗滌20分鐘，或可替代地在15℃和40℃洗滌20分鐘，如在實(shí)例中詳細(xì)說明的那樣。在流動自來水下徹底漂洗并且在黑暗中干燥之后，隨后測量帶有污漬的織物的光強(qiáng)度值作為洗滌性能的量度。具有0mg酶蛋白/L的測試用作空白并且對應(yīng)于來自洗滌劑的貢獻(xiàn)。優(yōu)選地，在洗滌步驟期間施加機(jī)械作用，例如以將洗滌溶液與織物一起振搖、轉(zhuǎn)動或攪拌的形式施加。AMSA洗滌性能實(shí)驗(yàn)可以在以下詳細(xì)說明的實(shí)驗(yàn)條件下實(shí)施：表A：實(shí)驗(yàn)條件表B：標(biāo)準(zhǔn)洗滌劑J通過向測試系統(tǒng)添加CaCl2、MgCl2和NaHCO3(Ca2+:Mg2+:HCO3-＝2:1:4.5)，將水硬度調(diào)節(jié)至6°dH。在洗滌之后，將紡織品用自來水沖洗并干燥。表C：實(shí)驗(yàn)條件表D：標(biāo)準(zhǔn)洗滌劑A化合物化合物的含量(％w/w)活性組分％(％w/w)LAS12.0011.60AEOS，SLES17.634.90大豆脂肪酸2.752.48可可脂肪酸2.752.80AEO11.0011.00氫氧化鈉1.751.80乙醇/丙-2-醇3.002.70/0.30MPG6.006.00丙三醇1.711.70TEA3.333.30甲酸鈉1.001.00檸檬酸鈉2.002.00DTMPA0.480.20PCA0.460.18苯氧基乙醇0.500.50H2O，離子交換33.6433.64將水硬度調(diào)節(jié)至15°dH，通過添加CaCl2、MgCl2和NAHCO3(Ca2+:Mg2+:HCO3-＝4:1:7.5)至測試系統(tǒng)中。在洗滌之后，將紡織品用自來水沖洗并干燥。洗滌性能可以被測量為亮度，表達(dá)為當(dāng)用白光照亮?xí)r從樣品反射的光的強(qiáng)度。當(dāng)樣品受到污染時，反射光的強(qiáng)度低于干凈樣品的反射光的強(qiáng)度。因此，反射光的強(qiáng)度可以用于測量洗滌性能。使用專業(yè)平板掃描儀(EPSONExpression10000XL,EPSON)進(jìn)行顏色測量，該掃描儀用于捕獲所洗滌紡織品的圖像。為了從掃描圖像中提取光強(qiáng)度的值，將來自圖像的48→24位彩色像素值轉(zhuǎn)化為紅色、綠色和藍(lán)色(RGB)的值。通過將RGB值作為向量相加在一起并然后考慮所得向量的長度可以計(jì)算強(qiáng)度值(Int)：紡織品：紡織品樣品CS-28(棉花上的大米淀粉)獲得自試驗(yàn)材料BV中心，郵箱120，3133KT，弗拉爾丁恩，荷蘭。表E：變體的洗滌性能表F：變體的洗滌性能序列表<110>諾維信公司<120>α-淀粉酶變體以及對其進(jìn)行編碼的多核苷酸<130>12909-WO-PCT<160>20<170>PatentIn3.5版本<210>1<211>485<212>PRT<213>人工序列<220><223>合成構(gòu)建體<400>1HisHisAsnGlyThrAsnGlyThrMetMetGlnTyrPheGluTrpTyr151015LeuProAsnAspGlyAsnHisTrpAsnArgLeuAsnSerAspAlaSer202530AsnLeuLysSerLysGlyIleThrAlaValTrpIleProProAlaTrp354045LysGlyAlaSerGlnAsnAspValGlyTyrGlyAlaTyrAspLeuTyr505560AspLeuGlyGluPheAsnGlnLysGlyThrValArgThrLysTyrGly65707580ThrArgSerGlnLeuGlnAlaAlaValThrSerLeuLysAsnAsnGly859095IleGlnValTyrGlyAspValValMetAsnHisLysGlyGlyAlaAsp100105110AlaThrGluMetValArgAlaValGluValAsnProAsnAsnArgAsn115120125GlnGluValThrGlyGluTyrThrIleGluAlaTrpThrArgPheAsp130135140PheProGlyArgGlyAsnThrHisSerSerPheLysTrpArgTrpTyr145150155160HisPheAspGlyValAspTrpAspGlnSerArgArgLeuAsnAsnArg165170175IleTyrLysPheArgGlyHisGlyLysAlaTrpAspTrpGluValAsp180185190ThrGluPheGlyAsnTyrAspTyrLeuMetTy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pTrpAspGlnSerArgArgLeuAsnAsnArg165170175IleTyrLysPheArgGlyHisGlyLysAlaTrpAspTrpGluValAsp180185190ThrGluAsnGlyAsnTyrAspTyrLeuMetTyrAlaAspIleAspMet195200205AspHisProGluValValAsnGluLeuArgAsnTrpGlyValTrpTyr210215220ThrAsnThrLeuGlyLeuAspGlyPheArgIleAspAlaValLysHis225230235240IleLysTyrSerPheThrArgAspTrpIleAsnHisValArgSerAla245250255ThrGlyLysAsnMetPheAlaValAlaGluPheTrpLysAsnAspLeu260265270GlyAlaIleGluAsnTyrLeuGlnLysThrAsnTrpAsnHisSerVal275280285PheAspValProLeuHisTyrAsnLeuTyrAsnAlaSerLysSerGly290295300GlyAsnTyrAspMetArgAsnIlePheAsnGlyThrValValGlnArg305310315320HisProSerHisAlaValThrPheValAspAsnHisAspSerGlnPro325330335GluGluAlaLeuGluSerPheValGluGluTrpPheLysProLeuAla340345350TyrAlaLeuThrLeuThrArgGluGlnGlyTyrProSerValPheTyr355360365GlyAspTyrTyrGlyIleProThrHisGlyValProAlaMetArgSer370375380LysIleAspProIleLeuGluAlaArgGlnLysTyrAlaTyrGlyLys385390395400GlnAsnAspTyrLeuAspHisHisAsnIleIleGlyTrpThrArgGlu405410415GlyAsnThrAlaHisProAsnSerGlyLeuAlaThrIleMetSerAsp420425430GlyAlaGlyGlySerLysTrpMetPheValGlyArgAsnLysAlaGly435440445GlnValTrpSerAspIleThrGlyAsnArgThrGlyThrValThrIle450455460AsnAlaAspGlyTrpGlyAsnPheSerValAsnGlyGlySerValSer465470475480IleTrpValAsnLys485<210>5<211>1455<212>DNA<213>人工序列<220><223>合成構(gòu)建體<400>5catcataacggtacgaacgggacaatgatgcaatactttgaatggtatctacctaatgac60ggaaatcattggaatcgattaaactctgatgcgagtaaccttaaaagcaaagggattaca120gcggtgtggattcctccagcatggaagggcgcttctcaaaatgacgtaggatacggagcc180tatgacctgtatgatctgggagaatttaatcaaaaaggtaccgtccgtacaaaatatgga240acacgtagtcagttacaagctgcggtaacctccttaaaaaataatggaattcaagtatat300ggtgacgttgttatgaatcacaaaggtggcgcagacgctactgaaatggtaagggccgtt360gaagtgaatcccaataaccgtaaccaagaagtgactggtgaatataccattgaagcttgg420actagatttgattttccagggcgaggaaatactcattctagctttaaatggagatggtat480cattttgatggtgtggattgggatcagtcacgtagactgaacaatcgcatctataaattt540agaggccatggcaaagcttgggattgggaagttgatacggaatttggtaattatgattat600ttaatgtacgctgattatgatatggatcacccagaagtagtaaatgaattaagaaattgg660ggtgtttggtacacaaacacattaggactcgatggatttagaatagatgcggttaaacat720ataaagtatagctttacgcgcgattggattaatcacgttagaagtgcaacaggtaaaaat780atgtttgcggttgctgagttttggaagaatgatttaggtgcaattgaaaactatctgcag840aaaacaaactggaaccattcagtctttgatgtgccgttacattataatctttataatgca900tcaaaaagcggagggaactatgatatgcgaaacatatttaatggaacggttgttcaacga960catccaagtcatgctgtaacatttgttgataatcatgattcgcagcctgaagaagcatta1020gaatcttttgttgaagaatggtttaaaccattagcgtatgcgcttacattaacgcgtgaa1080caaggatacccttctgtattttacggagattattatgggattccaacacatggagtgcca1140gcaatgagatcaaaaatcgatccgattttagaagcacgtcaaaagtatgcatacggaccc1200cagcacgattatcttgaccacccggatgtgatcggatggacgagggaaggtgacagctcc1260catcctaaatcaggtttggccactttaatcacggacggacccggcggatcaaagcggatg1320tatgccggcctgaaaaatgccggcgagacatggtatgacataacgggcaaccgttcagat1380actgtaaaaatcggatctgacggctggggagagtttcatgtaaacgatgggtccgtctcc1440atttatgttcagaaa1455<210>6<211>1449<212>DNA<213>人工序列<220><223>合成構(gòu)建體<400>6catcataacggtacgaacgggacaatgatgcaatactttgaatggtatctacctaatgac60ggaaatcattggaatcgattaaactctgatgcgagtaaccttaaaagcaaagggattaca120gcggtgtggattcctccagcatggaagggcgcttctcaaaatgacgtaggatacggagcc180tatgacctgtatgatctgggagaatttaatcaaaaaggtaccgtccgtacaaaatatgga240acacgtagtcagttacaagctgcggtaacctccttaaaaaataatggaattcaagtatat300ggtgacgttgttatgaatcacaaaggtggcgcagacgctactgaaatggtaagggccgtt360gaagtgaatcccaataaccgtaaccaagaagtgactggtgaatataccattgaagcttgg420actagatttgattttccagggcgaggaaatactcattctagctttaaatggagatggtat480cattttgatggtgtggattgggatcagtcacgtagactgaacaatcgcatctataaattt540agaggcaaagcttgggattgggaagttgatacggaaaatggtaattatgattatttaatg600tacgctgatattgatatggatcacccagaagtagtaaatgaattaagaaattggggtgtt660tggtacacaaacacattaggactcgatggatttagaatagatgcggttaaacatataaag720tatagctttacgcgcgattggattaatcacgttagaagtgcaacaggtaaaaatatgttt780gcggttgctgagttttggaagaatgatttaggtgcaattgaaaactatctgcagaaaaca840aactggaaccattcagtctttgatgtgccgttacattataatctttataatgcatcaaaa900agcggagggaactatgatatgcgaaacatatttaatggaacggttgttcaacgacatcca960agtcatgctgtaacatttgttgataatcatgattcgcagcctgaagaagcattagaatct1020tttgttgaagaatggtttaaaccattagcgtatgcgcttacattaacgcgtgaacaagga1080tacccttctgtattttacggagattattatgggattccaacacatggagtgccagcaatg1140agatcaaaaatcgatccgattttagaagcacgtcaaaagtatgcatacggaccccagcac1200gattatcttgaccacccggatgtgatcggatggacgagggaaggtgacagctcccatcct1260aaatcaggtttggccactttaatcacggacggacccggcggatcaaagcggatgtatgcc1320ggcctgaaaaatgccggcgagacatggtatgacataacgggcaaccgttcagatactgta1380aaaatcggatctgacggctggggagagtttcatgtaaacgatgggtccgtctccatttat1440gttcagaaa1449<210>7<211>485<212>PRT<213>芽孢桿菌屬物種<400>7HisHisAsnGlyThrAsnGlyThrMetMetGlnTyrPheGluTrpHis151015LeuProAsnAspGlyAsnHisTrpAsnArgLeuArgAspAspAlaSer202530AsnLeuArgAsnArgGlyIleThrAlaIleTrpIleProProAlaTrp354045LysGlyThrSerGlnAsnAspValGlyTyrGlyAlaTyrAspLeuTyr505560AspLeuGlyGluPheAsnGlnLysGlyThrValArgThrLysTyrGly65707580ThrArgSerGlnLeuGluSerAlaIleHisAlaLeuLysAsnAsnGly859095ValGlnValTyrGlyAspValValMetAsnHisLysGlyGlyAlaAsp100105110AlaThrGluAsnValLeuAlaValGluValAsnProAsnAsnArgAsn115120125GlnGluIleSerGlyAspTyrThrIleGluAlaTrpThrLysPheAsp130135140PheProGlyArgGlyAsnThrTyrSerAspPheLysTrpArgTrpTyr145150155160HisPheAspGlyValAspTrpAspGlnSerArgGlnPheGlnAsnArg165170175IleTyrL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