JP2016127822A - サブチリシン変異体を含む組成物及び方法 - Google Patents
サブチリシン変異体を含む組成物及び方法 Download PDFInfo
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- JP2016127822A JP2016127822A JP2015235701A JP2015235701A JP2016127822A JP 2016127822 A JP2016127822 A JP 2016127822A JP 2015235701 A JP2015235701 A JP 2015235701A JP 2015235701 A JP2015235701 A JP 2015235701A JP 2016127822 A JP2016127822 A JP 2016127822A
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- subtilisin
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Abstract
【解決手段】バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列に対して特定のアミノ酸置換の組み合わせを含むアミノ酸配列を有する、サブチリシン変異体であって、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して−5〜+5である、タンパク質分解活性を有する成熟型の単離されたサブチリシン変異体。
【選択図】なし
Description
N、X111V−X188D、X062E−X188D、X016S−X188D、X148I−X188D、X022A−X188D、X128N−X188D、X101A−X188D、X104L−X188D、X089P−X188D、X129E−X188D、X159E−X188D、X186H−X188D、X103G−X188D、X158E−X188D、X016S−X022A、X016S−X104L、X022A−X104L、X101A−X104L、X062E−X104L、X103G−X104L、X089P−X104L、X159E−X209E、X111V−X209E、X101A−X209E、X016S−X209E、X128N−X209E、X148I−X209E、X129E−X209E、X062E−X209E、X022A−X209E、X103G−X209E、X158E−X209E、X188D−X209E、X104L−X209E、X089P−X209E、及びX186H−X209Eから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
043R−X241R、X009A−X043R−X078R、X004R−X020R−X024R−X244R、X020R−X022R−X078R−X242R、X020R−X024R−X242R−X249R、X004R−X009A−X078R−X241R、X009A−X043R−X078R−X242R、X004R−X020R−X024R、X009A−X043R−X212F、X020R−X043R−X212F、X024R−X078R−X212F、X009A−X020R−X024R−X043R、X009A−X022R−X043R−X078R、X020R−X022R−X212F−X241R、X020R−X043R−X212F−X241R、X009A−X043R−X241R、X020R−X043R−X271L、X020R−X022R−X078R−X241R、X020R−X024R−X043R−X242R、X020R−X022R−X043R−X241R、X009A−X020R−X043R−X212F、X004R−X009A−X020R−X024R−X242R、X020R−X043R−X249R−X271L、X020R−X022R−X024R−X242R、X009A−X022R−X078R−X212F、X020R−X043R−X242R−X271L、X009A−X022R−X078R−X212F−X241R、X004R−X020R−X024R−X249R、X020R−X022R−X271L、X020R−X022R−X043R−X212F、X004R−X020R−X024R−X043R−X242R、X004R−X020R−X024R−X043R、X004R−X009A−X022R−X078R−X212F、X020R−X022R−X078R−X212F−X241R、及びX020R−X022R−X269Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X232V−X245R−X248D、X016S−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X158E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X232V−X245R−X248D、X022A−X024R−X101G−X103
A−X104I−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X159E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024K−X101G−X103A−X104I−X128N−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X148I−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X148I−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、及びX101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
X158E−X186H−X249R−X271F、X158E−X186H−X249R、X101A−X158E−X186H−X249R、X104L−X158E−X188D−X249R−X271F、X016S−X128N−X158E−X186H、X104L−X128N−X186H−X188D−X249R、X016S−X101A−X128N−X186H、X016S−X062E−X128N−X186H−X271F、X016S−X128N−X186H−X271F、X128N−X129E−X186H、X158E−X186H−X249R−X271F、X016S−X158E−X249R、X016S−X158E−X186H−X249R、X016S−X022A−X158E−X186H−X271F、X089P−X101A−X129E−X186H、X022A−X128N−X158E−X186H、X101A−X104L−X128N−X158E−X186H、X022A−X128N−X186H−X188D−、X062E−X104L−X158E−X186H−X188D−X249R、X022A−X158E−X186H−X249R−X271F、X022A−X104L−X158E−X249R、X101A−X111V−X129E、X016S−X158E−X249R−X271F、X016S−X111V−X188D−、X022A−X104L−X186H−X188D−X249R、及びX104L−X148I−X188D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
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249R、X018R−X020R−X024R−X076D−X183D−X211Q−X215F−X249R、X024R−X076D−X104I、X018R−X076D−X101G−X232V、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X215F−X249R、X018R−X024R−X031F−X076D−X116A−X183D−X211Q−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X213A−X249R−X269S、X018R−X020R−X024R−X076D−X101A−X116A−X198L−X215F−X249R、X018R−X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X114T−X198L−X211Q−X215F−X249R、X024R−X043R−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X024R−X076D−X103A−X104I−X232V、X018R−X020R−X022W−X024R−X076D−X101A−X198L−X211Q−X215F−X249R、X101G−X104I−X232V、X018R−X022W−X024R−X076D−X183D−X198L−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X183D−X213A−X249R、X018R−X024R−X076D−X101A−X183D−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X211Q−X213A−X249R、X018R−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X211Q−X215F−X249R−X260A、X076D−X249R、X018R−X022W−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X116A−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X249R、X076D−X104I−X249R、X020R−X022W−X101A−X103A−X104I−X116A−X183D−X211Q−X213A−X215F−X232V−X245R、X024R−X043R−X045T−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X018R−X020R−X022W−X024R−X076D−X183D−X198L−X215F−X249R、X018R−X076D−X101G−X103A、X020R−X024R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R、X101G−X103A−X232V、X024R−X076D−X101G−X232V、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X183D−X198L−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X116A−X156V−X183D−X211Q−X215F−X249R−X269S、X045T−X076D−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X249R、X018R−X020R−X022W−X024R−X076D−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X249R、X018R−X076D−X101G、X018R−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X249R、X018R−X076D−X232V、X018R−X020R−X024R−X076D−X101A−X232V−X245R、X018R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X018R−X022W−X024R−X076D−X183D−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X211Q−X213A−X237D−X249R、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R−X275S、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X024R−X076D、X018R−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X076D−X104I−X232V−X249R、X018R−X076D−X103A−X232V、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X175E−X183D−X211Q−X215F−X249R、X018R−X020R−X043D−X078R−X101G−X103A−X104I−X217E−X232V−X245R−X273E、X020R−X024R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X005S−X101G−X103A−X104I−X232V−X245R−X249R、X103A−X104I−X232V、X018R−X020R−X024R−X068A−X076D−X101A−X116A−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X198L−X215F−X249R−X275S、X018R−X024R−X076D−X183D−X198L−X211Q−X213A−X249R、及びX043D−X045T−X101G−X103A−X104I−X232V−X245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
R、X024R−X076D−X101G−X103A−X104I−X232V−X245R、X076D−X101G−X103A−X104I−X232V−X242R−X245R、X018R−X020R−X024R−X076D−X217E−X249R、X018R−X024R−X043R−X076D−X217E−X249R、X018R−X024R−X043D−X076D−X242R−X249R、X018R−X020R−X024R−X043R−X076D−X249R、X020R−X101A−X103G−X104V−X232V−X245R、X043D−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X076D−X217E−X249R−X269R、及びX018R−X024R−X076D−X217E−X242R−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
D−X232V−X245R−X248D−X271F、X022A−X103A−X104I−X118R−X129E−X159D−X188D−X232V−X245R−X248D−X271F、X022A−X024R−X043R−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X248D、X022A−X062E−X103A−X104I−X118R−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X101D−X103A−X104I−X118R−X129E−X159D−X188D−X217D−X232V、X022A−X024R−X103A−X104I−X159D−X188D−X217D−X232V−X248D、X022A−X024R−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X217D−X232V−X248D−X271F、及びX022A−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X245R−X248D−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
01S、X024R−X239Q、X033S−X118R−X209A−、X078R−X086W、X235F−X243F、X024R−X209A−X235F、X118R−X172V、X017Y−X024R−X033S−X086W、X033S−X148F、X024R−X118R−X235F、X033S−X078R、X033S−X243F、X024C−X033S、X118R−X194T、X033S−X209A、X118R−X209A−X235F、X024R−X033S−X209A−X243F、X024R−X033S−X235F、X024R−X033S−X118R−X235F、X024R−X141G、X024R−X274I、X024R−X033S−X209A、X086W−X235F、X024R−X209A−X243F、X004E−X033S−X078R、X086W−X209A−X235F、X015T−X033S、X033S−X086W−X156L−X209A、X024R−X118R−X243F−X269H、X209A−X235F、X024R−X247H、X024R−X033S−X228T、X078R−X235F、X024R−X033S−X174V−X235F、X024R−X235F−X243F、X024R−X033S−X235F−X241R、X024R−X033S−X151V、X024R−X104A、X033S−X048T、X012H−X104A−X118R、X118R−X235F、X033S−X253A、X143A−X209A、X024R−X033S−X243F、X033S−X239T、X209A−X243F、X024R−X033S−X129H−X184D−X253M、X024R−X085V−X086W−X118R−X235F、X024R−X272P、及びX024R−X269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R−X271G、X101G−X103A−X104I−X129Q−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X130A−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129Q−X158E−X188D−X217E−X232V−X245R−X248D−X249R、及びX024R−X101G−X103A−X104I−X128L−X130A−X158E−X188D−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
49R、T022A−H249R、S128N−H249R、S103G−H249R、E089P−H249R、T022A−L111V、S101A−L111V、A016S−L111V、V104L−L111V、N062E−L111V、S103G−L111V、E089P−L111V、A016S−L148I、N062E−L148I、T022A−L148I、P129E−L148I、V104L−L148I、S103G−L148I、S128N−L148I、S101A−L148I、E089P−L148I、L111V−L148I、A016S−N062E、T022A−N062E、N062E−P129E、T022A−P129E、S128N−P129E、A016S−P129E、S101A−P129E、V104L−P129E、E089P−P129E、S103G−P129E、L111V−P129E、N062E−R186H、S128N−R186H、S101A−R186H、T022A−R186H、A016S−R186H、A158E−R186H、E089P−R186H、P129E−R186H、G159E−R186H、S103G−R186H、V104L−R186H、L111V−R186H、L148I−R186H、N062E−S101A、T022A−S101A、A016S−S101A、E089P−S101A、N062E−S103G、T022A−S103G、A016S−S103G、S101A−S103G、E089P−S103G、N062E−S128N、A016S−S128N、T022A−S128N、S101A−S128N、V104L−S128N、E089P−S128N、S103G−S128N、L111V−S128N、L111V−S188D、N062E−S188D、A016S−S188D、L148I−S188D、T022A−S188D、S128N−S188D、S101A−S188D、V104L−S188D、E089P−S188D、P129E−S188D、G159E−S188D、R186H−S188D、S103G−S188D、A158E−S188D、A016S−T022A、A016S−V104L、T022A−V104L、S101A−V104L、N062E−V104L、S103G−V104L、E089P−V104L、G159E−Y209E、L111V−Y209E、S101A−Y209E、A016S−Y209E、S128N−Y209E、L148I−Y209E、P129E−Y209E、N062E−Y209E、T022A−Y209E、S103G−Y209E、A158E−Y209E、S188D−Y209E、V104L−Y209E、E089P−Y209E、及びR186H−Y209Eから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−Y209E、P129E−Y209E、N062E−Y209E、T022A−Y209E、S103G−Y209E、A158E−Y209E、S188D−Y209E、V104L−Y209E、E089P−Y209E、R186H−Y209E、N018R−W241R、G020R−W241R、S024R−W241R、S009A−W241R、G020R−W241R、V004R−W241R、N043R−W241R、S078R−W241R、T022R−W241R、G115R−W241R、A001R−W241R、S212F−W241R、L082R−W241R、N018R−V244R、S024R−V244R、S078R−V244R、G020R−V244R、S212F−V244R、S009A−V244R、L082R−V244R、A001R−V244R、N043R−V244R、T022R−V244R、V004R−V244R、G115R−V244R、W241R−V244R、S242R−V244R、A001R−V004R、S009A−T022R、N018R−T022R、G020R−T022R、V004R−T022R、A001R−T022R、S024R−S242R、N018R−S242R、V004R−S242R、G020R−S242R、S212F−S242R、L082R−S242R、S078R−S242R、A001R−S242R、S009A−S242R、T022R−S242R、G115R−S242R、N043R−S242R、W241R−S242R、N018R−S212F、T022R−S212F、V004R−S212F、S024R−S212F、A001R−S212F、G115R−S212F、G020R−S212F、S009A−S212F、N043R−S212F、S078R−S212F、L082R−S212F、S009A−S078R、G020R−S078R、S024R−S078R、T022R−S078R、N018R−S078R、V004R−S078R、A001R−S078R、N043R−S078R、T022R−S024R、G020R−S024R、N018R−S024R、A001R−S024R、V004R−S024R、S009A−S024R、V004R−S009A、A001R−S009A、S242R−N269R、S024R−N269R、G020R−N269R、T022R−N269R、H249R−N269R、S212F−N269R、N043R−N269R、V244R−N269R、A001R−N269R、N018R−N269R、S078R−N269R、S009A−N269R、G115R−N269R、W241R−N269R、V004R−N269R、L082R−N269R、N018R−N043R、G020R−N043R、V004R−N043R、T022R−N043R、S009A−N043R、A001R−N043R、S024R−N043R、S009A−N018R、V004R−N018R、A001R−N018R、S024R−L082R、S009A−L082R、N018R−L082R、A001R−L082R、S078R−L082R、G020R−L082R、T022R−L082R、V004R−L082R、N043R−L082R、N043R−H249R、G020R−H249R、V004R−H249R、N018R−H249R、S009A−H249R、S212F−H249R、T022R−H249R、S024R−H249R、G115R−H249R、A001R−H249R、L082R−H249R、S242R−H249R、W241R−H249R、V244R−H249R、S078R−H249R、N018R−G115R、G020R−G115R、T022R−G115R、S078R−G115R、S009A−G115R、V004R−G115R、A001R−G115R、L082R−G115R、N043R−G115R、S024R−G115R、S009A−G020R、N018R−G020R、V004R−G020R、A001R−G020R、S009A−E271L、G020R−E271L、S024R−E271L、V244R−E271L、W241R−E271L、N043R−E271L、T022R−E271L、H249R−E271L、S212F−E271L、G115R−E271L、S242R−E271L、S078R−E271L、V004R−E271L、N269R−E271L、A001R−E271L、N018R−E271L、及びL082R−E271Lから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、この変異体の合計正味電荷が、バチルス・レンタス(Bacillus lentus)のサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、この正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、このプロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンス(Bacillus amyloliquefaciens)のサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体を提供する。
45R−X248D−X76D及びX101G−X103A−X104I−X159E−X232V−X245R−X248D−X271Fのうちの1つ以上を含み、上記変異体は、配列番号1のアミノ酸配列を有するB.レンタスのサブチリシンGG36プロテアーゼと比較して0、−1、−2、−3、−4又は−5の正味電荷、好ましくは0、−1、−2又は−3の正味電荷を有する。これらのプロテアーゼ変異体は、イオン強度の低い、又は洗剤濃度の低い水性洗浄液に特に好ましいものであり得る。
G020R−S024R−N076D−H249R、S024R−N043R−A230E−S242R、N018R−S024R−N043D−A230E、G020R−N076D、N018R−S024R−N043D−N076D−H249R、S024R−N043R−N076D−H249R、N018R−S024R−R045T−S242R、G020R−N043D−N076D−A230E−H249R、G020R−N043R−R045T−S242R、N018R−S024R−N076D−H249R、N018R−G020R−S024R−N043D−R045T−L233I−S242R、S024R−N043R−A230E、N018R−G020R−N043D、N043R−S242R−H249R、G020R−N043R−R045T−A230E、N043R−N076D−S242R−H249R、G020R−S024R−R045T−A230E−S242R、S024R−R045T−N076D−A230E−S242R−H249R、S024R−R045T、S024R−N043R−R045T−N076D−A230E−H249R、N018R−S024R−N043D−R045T−H249R、N018R−N043R−R045T−H249R、S024R−N043R−S242R、N018R−G020R−N043R−N076D−H249R、G020R−S024R−N043D−H249R、G020R−N043R−A230E−S242R、G020R−N043R−S242R、N018R−N043R−N076D−A230E、G020R−S024R−N043D−S242R、G020R−N043R−A230E、N018R−G020R−N043R−N076D−S242R−H249R、N043D−R045T−N076D−H249R、N018R−N043R−S242R−H249R、N018R−G020R−N043R−R045T−S242R、N018R−G020R−N043D−A230E−S242R、G020R−S024R−N043R−R045T−H249R、S024R−N043R−H249R、G020R−S024R−K27E−N043R−N076D−A230E、S024R−N043R−R045T−S242R、N018R−G020R−S024R−N043R−R045T−N076D−A230E、G020R−N043R−N076D−A230E−H249R、N018R−N043R−R045T−S242R、G020R−S242R−H249R、N018R−N043R−N076D−A230E−S242R−H249R、N018R−S024R−N076D、G020R−S024R−K27R−N043D−S242R−H249R、N018R−G020R−S024R−N043D−N076D−S242R、N018R−N043R−N076D−S242R−H249R、N018R−S024R−N043D−A230E−H249R、N018R−G020R−N043D−H249R、N018R−G020R−N043D−R045T−N076D−S242R、S024R−N043R−N076D−A230E−S242R、G020R−S024R−T38I−N043R−R045T−N076D−S242R−H249R、N018R−G020R−N043R、N018R−S024R−R045T−A230E−S242R、N018R−G020R−H249R、S024R−N043R−N076D、N018R−G020R−S024R−N043R−R045T−N076D−H249R、N018R−N043D−R045T−N076D−S242R−H249R、S024R−N043D−S242R−H249R、N018R−G020R−S024R−N043D−R045T−S242R、G020R−S024R−N043R−N076D、N018R−G020R−N043D−R045T−A230E−S242R、G020R−S024R−N043R−R045T−N076D−S242R−H249R、N018R−N043R−R045T−N076D−S242R、N018R−G020R−N043R−N076D−A230E−S242R、N018R−S024R−N043D−H249R、N018R−S024R−N043R−R045T−A230E−H249R、N018R−G020R−N043R−R045T−N076D−H249R、N018R−S024R−S242R、N018R−N043R−R045T−N076D−A230E−S242R、R045T−S242R−H249R、N018R−S024R−N043D−S242R、N018R−G020R−N043D−R045T−S240P、S024R−N043R−R045T−S242R−H249R、N018R−S024R−V30S−L31S−D32I−T33Q−G34V−I35F、N018R−G020R−N043R−N076D、G020R−N043D−R045T−N076D−S242R−H249R、N018R−S024R−N043D−A230E−S242R、N018R−S024R−N043D−S242R−H249R、S024R−N043D−R045T−S242R−H249R、N043R−A230E−H249R、S024R−N043R−N076D−A230E−H249R、G020R−S024R−N043D−N076D−H249R、S024R−R045T−S242R−A273V、G020R−S024R−R045T−N076D−S242R−H249R、N018R−S024R−N043D−N076D−S242R、N018R−N043R−N076D−A230E−H249R、N018R−G020R−N043R−R045T−H249R、N018R−N043R−R045T−A230E−S242R、G020R−S024R−N043D−R045T−A230E−S242R、N018R−N043D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−G020R−N076D、N018R−G020R−N043D−N076D−S242R−H249R、G020R−S024R−N043D−N076D−S242R−H249R、N043D−S242R−H249R、N018R−G020R−S024R−N043R−N076D、N018R−G020R−N043D−R045T−N076D−H249R、N018R−G020R−N043R−R045T−N076D−A230E−H249R、N018R−N076D−S242R、G020R−N043R−H249R、N018R−N076D−S242R−H249R、N018R−S024R−R045T−A230E−H249R、A230E−H249R、N018R−R045T−H249R、G020R−N043R−N076D、N043R−R045T−H249R、N018R−N043D−N076D−S242R−H249R、N043R−N076D−H249R、N018R−R045T、G020R−N076D−A230E−S242R、G020R−S024R−N043D−R045T、S024R−N043D−N076D−S242R−H249R、G020R−R045T−H249R、N043R−N076D−S153A−H249R、N043R−N076D−A230E−H249R、N018R−N043D−N076D−H249R、及びG020R−N043R−N076D−V227Iから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、及びS101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の
組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
3A−V104I−A232V−Q245R、S101G−S103A−V104I−A232V−Q245R−E271L、G020R−N043R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−G025R−N116A−Y167W、N018R−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−A232V−Q245R、S078R−S103N−S106G−Y167W−Q236N、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101A−H120F−A194F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−S212F−A232V−Q245R、G020R−S144R−N185I−L233C−Q236N、G023A−S078R−S216F−Q236N−H249R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−G115R−A232V−Q245R、P052N−S078R−S103N−L148I−T213A、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G025R−E089I−N116A−P239S−A270C、S024R−S101G−S103A−V104I−A232V−Q245R、L148I−T213A−N252R、S024R−G025R−N183D−Y192W−P239S、G046R−A194F−S212M、V104L−L217E−T224A−H249R−N252R、G023A−Y091F−V121F−Y192W−Q236N、S101G−S103A−V104I−A232V−V244R−Q245R、S099F−S144R−Y167W−N252R、S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S101G−S103A−V104I−A232V−Q245R、T022W−S078R−Y167W−S212M−A270C、V121F−N252R−A270C、G020R−S103N−S216F−Q236N−N252R、N043R−S101G−S103A−V104I−A232V−Q245R−H249R、G023A−P052N−Y192W−I198L−N252R、G025R−G046R−V121F、S024R−S078R−V104L−N116A−N183D、G046R−Q059A−S103N−G211Q−S212M、G020R−P052N−N062Q−Y091F−Y192W、G023A−P052N−S144R−Y192W−S216F、S101G−S103A−V104I−A232V−S242R−Q245R、P052N−S103N−N116A−L148I−Y192W、E089I−N116A−N117F−T224A−H249R、S144R−G211Q−N238L−P239S−H249R、N043A−N062Q−A194F−G211Q、G020R−S024R−P052N−Q059A−S216F、S024R−Y167W−T224A−H249R、T057R−Y167W−H249R、G025R−S103N−R186K−A194F−T224A、S105T−S128N−S144R−L148I−S212M、G020R−Q059A−S144R−Y192W−T224A、S024R−N043A−N117F−A194F−G211Q、N117F−A194F−T213A−A270C、S078R−Y091F−V121F−L233C−N252R、T057R−S099F−S105T−I198L−T213A、G023A−Y091F−S101A−I198L−N252R、N062Q−S103N−V121F−S144R−H249R、N043R−S101G−S103A−V104I−A232V−S242R−Q245R、G023A−S024R−N117F−S212M−S216F、V104L−T213A−S216F、A194F−G211Q−Q236N、N062Q−S103N−N117F−A194F、S024R−N062Q−V104L−S106G−H249R、T057R−E089I−I198L、G046R−Q059A−S106G−L217E−H249R、N117F−T213A−A215F、S101A−H120F−Y192W−A215F−T224A、N043A−T057R−N117F−S144R−N183D、G046R−N183D−N238L、G025R−N043A−E089I−N117F、S078R−V104L−T213A−A215F−T224A、Y091F−S099F−S101A−S105T−Y167W、S106G−N117F−N238L、G046R−E089I−Y091F−S101A−N116A、G020R−N062Q−E089I−R186K−S212M、T057R−S099F−V121F−N185I−Y192W、G046R−E089I−Y192W−L233C−A270C、E089I−N117F−N185I−A215F−L233C、P052N−V104L−N183D−S216F−H249R、S078R−S099F−N116A−R186K−T224A、G025R−S105T−S128N−S144R−A270C、S105T−G211Q−S216F、S024R−G046R−Y091F−V121F、S106G−N185I−S216F−Q236N、N062Q−S101A−Q236N−N252R−A270C、G025R−N043A−Y091F−I198L−A270C、G020R−G023A−V104L−Y192W−L233C、S024R−N043A−S105T−S106G−I198L、G020R−E089I−L217E、S024R−Y091F−I198L−A215F−P239S、G046R−E089I−S099F−R186K−S212M、V104L−H120F−R186K−S216F−N252R、T022W−A194F−T213A−L233C−N238L、S099F−S105T−S106G−A194F−S212M、E089I−S105T−N116A−A215F−S216F、G025R−N116A−H120F−T224A−A270C、N043A−Q059A−S101A−S216F−T224A、T057R−N183D−Q236N、G025R−N062Q−S128N−S144R−N185I、S103N−H120F−Y167W−I198L−L233C、T022W−E089I−S216F、S024R−S106G−N116A−S212M−T224A、G020R−P052N−S101A−I198L−L233C、E089I−Y091F−N185I−G211Q−A270C、L111I−A215F−P239S、S024R−N116A−R186K−L233C−Q236N、及びG023A−S103N−S106G−S212M−A215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−S103A−V104I−A232V−Q245R、N018R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S101G−S103A−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−S101G−V104I−A232V−H249R、G020R−T22W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−H249R、S024R−S101G−S103A−V104I−A232V−Q245R、G020R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−V104I−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A215F−A232V−Q245R、S024R−S103A−V104I−H249R、N018R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101G−V104I−Q245R、G020R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、S024R−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−Q245R、S024R−S103A−Q245R、S024R−S103A−V104I−Q245R、G020R−S078R−S101G−A232V−Q245R、N018R−S024R−N076D−V104I−H249R、N018R−S024R−V104I−H249R、S024R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−A215F−H249R、R019H−G020R−T022W−S078R−S101G−S103A−V104I−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S103A−V104I−A232V−Q245R、N018R−S103A−V104I−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−S024R−S101G−V104I−A232V、S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−S024R−S101G−V104I、G020R−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−Q245R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−N076D−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、A001T−N018R−S024R−N076D−N116A−T213A−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、N018R−S024R−N076D−T213A−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、G020R−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S101G−S103A−V104I、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−S103A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−G211Q−H249R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T
022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−S024R−N076D−A232V−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−Q245R、S024R−V104I−Q245R、S101G−A232V、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、S024R−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、S024R−S101G−V104I−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−V104I、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−T213A−H249R、S024R−V104I−H249R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−N076D−S103A−V104I−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q245R−E271G、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、S024R−S103A−M175L−A232V−H249R、N018R−S024R−N076D−N116A−T213A−H249R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−A232V、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、S024R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、S101G−S103A−V104I−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S103A−A232V、N018R−S024R−N076D−S101A−G211Q−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101G−A232V、A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、S024R−N076D−S103A−V104I−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S103A−V104I−A232V、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−A215F−
H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、S024R−N076D−V104I−Q245R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−N076D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、N018R−S024R−N076D−N116A−H249R、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−S101G−Q245R、S024R−N076D−S101G−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、S024R−S101G、N018R−T22W−S024R−N076D−T213A−A215F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−V104I、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S024R−N076D−Q245R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N018R−S103A、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−V104I、S101G−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、G020R−T02
2W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S103A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、S101G−H249R、S024R−N076D−S101G−S103A−V104I−M175L−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S103A−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−A232V、S024R−S103A−V104I、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−S103A−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、S103A−V104I−Q245R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、A016T−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101G、N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−A215F−H249R、N018R−V104I−A232V、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S101G−A232V−H249R、S103A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S024R−N076D−S103A−V104I−H249R、S024R−S101G−S103A−V104I、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N018R−N076D−A232V−H249R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、A232V−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N076D−V1
04I−Q245R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、S024R−S101G−S103A−A232V、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、S103A−A232V−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、S024R−S103A−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、S103A−A232V、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−A232V、N018R−T022W−S024R−N076D−S101A−N116A−H249R、G020R−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−N263S、S024R−N076D−S101G−V104I−A232V−H249R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、S024R−S101G−S103A、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−V104I−A232V、N018R−S024R−N076D−N183D−G211Q−H249R、G020R−N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N183D−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、S024R−N076D−A232V−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、G020R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N076D−S101G−S103A−Q245R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T22W−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−
I198L−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N076D−Q245R、N076D−S101G−V104I−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、G020R−S024R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S101G−S103A−V104I、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N076D−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−Q245R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N076D−V104I−A232V−Q245R、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N076D−S101G−S103A−V104I−A232V−H249R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、N076D−S101G−S103A−V104I−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N18
3D−I198L−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、S024R−N076D−S101G、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−N076D−S101G−I198T−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−N076D−V104I−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−V104I、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−
A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、及びN043D−R045T−S101G−S103A−V104I−A232V−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
3A−V104I−T213A−A232V−Q245R−N269R、S024R−A215F−N269R、N043R−S101A−N116A−T213A−A215F−N269R、N043R−S101A−T213A−N269R、G020R−S024R−N043R−R045T−N116A−T213A、S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−R045T−S101A−N116A−T213A−N269R、S024R−N043R−R045T−N269R、G020R−N043R−R045T−S101A−N269R、S024R−N043R−N116A−N269R、G020R−S024R−N043R−R045T、N043R−N116A−N269R、S024R−N043R−S101A−A215F−N269R、S024R−N043R−R045T−T213A−A215F−N269R、G020R−S024R−R045T−N269R、G020R−N043R−S101A−N116A−T213A−A215F、G020R−S101G−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N116A−N269R、G020R−S101A−N116A−N269R、S024R−N043R−A215F、G020R−S024R−T213A、S024R−N043R−S101A−A215F、G020R−S024R−N043R−R045T−N116A、G020R−S024R−N043R−R045T−S101A−N269R、G020R−S024R−S101A−A215F、G020R−S024R−N116A−T213A−A215F、G020R−S024R−N116A、G020R−S024R−S101A−N116A、N043R−T213A−A215F−N269R、S024R−S101A−N269R、S024R−N043R−N116A−A215F、G020R−T038A−N043R−S101A、G020R−S024R−N116A−A215F、S024R−N043R−S101A−T213A、P014L−G020R−S024R−N043R−R045T−S101A−A215F、G020R−S024R−A215F、G020R−N116A−A215F−N269R、G020R−R045T−N116A−N269R、G020R−S024R−N043R−R045T−A215F、及びG020R−S024R−N043R−R045T−N116A−T213A−A215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101G−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103G−V104V−G159E−A232V−Q245R−N248D−H249R、及びS101S−S103A−V104V−G159E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
3A−S024F−N062E−N116L−S188D−T213A、S024F−N062E−S188D−P239G、G023A−N043W−N062E−N116L−G118R−T213A、N062E−S188D−P239G、G020K−S024F−N062E−P239G、S024F−N116L−G118R−S188D−P239G、G020K−G023A−N062E−N116L−G118R−T213A、G020K−G023A−S024F−N062E−S188D−T213A−P239G、S024F−N043W−G118R−S188D、G023A−S024F−N116L−G118R−S188D−T213A、G020K−G023A−N043W−N116L−S188D−T213A−P239G、G023A−S024F−N116L−S188D−P239G、G023A−N043W−N116L−G118R−S188D、G023A−S024F−G118R−S188D−P239G、G023A−S024F−N043W−N062E−N116L−G118R、G020K−N043W−S188D−T213A、S024F−N062E−G118R−P239G、G023A−N043W−S188D−T213A、G020K−S024F−N043W−N062E−N116L−G118R−S188D−P239G、G020K−N116L−S188D−P239G、G020K−N043W−N062E−G118R、G020K−N043W−N116L−S188D−T213A、G020K−S024F、G023A−N043W−N116L−P239G、G023A−S024F−N043W−N116L−G118R−S188D−P239G、G020K−G023A−N043W−T213A、及びG023A−S024F−N062E−G118R−T213A−P239Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
N076D−S087D−H249R、N018R−G020R−S024R−N076D−V150L−H249R、N018R−S024R−N043R−N076D−S087D−H249R、N018R−S024R−N043R−N076D−V150L−H249R、N018R−S024R−N076D−S078R−S087D−H249R、N018R−S024R−N076D−S078R−V150L−H249R、N018R−S024R−N076D−S087D−H249R−N269R、N018R−S024R−N076D−S087D−S242R−H249R、N018R−S024R−N076D−S087D−V150L−H249R、N018R−S024R−N076D−V150L−H249R、N018R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−T022R−S024R−N076D−S087D−H249R、N018R−T022R−S024R−N076D−V150L−H249R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R、S024R−S087D−S101G−S103A−V104I−A232V−Q245R、S024R−S101G−S103A−V104I−V150L−A232V−Q245R、S078R−S087D−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−V150L−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−V150L−A232V−Q245R−H249R、S101G−S103A−V104I−V150L−A232V−Q245R−N269R、T022R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−N076D−V150L−H249R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−S024R−N043D−N076D−S087D−H249R、N018R−S024R−N076D−S087D−H249R、N018R−S024R−N076D−V150L−S242R−H249R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R−N269R、N076D−S101G−S103A−V104I−V150L−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−S242R−Q245R、S101G−S103A−V104I−V150L−A232V−Q245R、N076D−S087D−S101G−S103A−V104I−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−Q245R、及びS101G−S103A−V104I−V150L−A232V−S242R−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
サブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
09L、P210R、P210V、P210L、G211Q、G211R、S212I、S212M、S212F、T213A、Y214F、A215N、A215D、A215E、A215H、A215F、S216F、S216A、L217E、L217N、L217D、N218D、N218P、N218E、T224A、T224G、V227I、A230E、A231I、A231C、A232V、L233C、V234F、K235F、Q236F、Q236N、Q236H、N238R、N238K、N238L、P239K、P239G、P239R、P239R、P239H、P239T、P239N、P239S、P239F、S240R、W241R、S242L、S242R、N243F、N243R、V244R、Q245R、I246S、N248D、N248V、N248I、N248R、H249R、H249T、L250I、K251R、K251S、N252I、N252F、N252R、N252K、N252H、T253I、T253R、T253F、A254C、S256N、G258R、T260V、T260I、L262D、L262H、Y263F、S265F、L267V、L267N、L267M、N269I、N269R、A270C、E271I、E271H、E271V、E271H、E271M、E271L、E271P、E271A、E271F、E271T、A272F、A272F、A272R、A273F、A273I、及びT274Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
P210R、S212I、S212F、Y214F、A215N、A215D、A215E、L217E、L217N、T224A、A230E、A231I、Q236F、N238R、N238K、P239K、P239G、P239R、P239S、W241R、S242R、S242L、N243R、V244R、N248I、N248V、H249R、L250I、N252R、T253R、L262D、Y263F、S265F、L267V、L267N、N269I、N269R、E271F、E271I、E271H、E271P、E271T、E271V、E271L及びA272Fからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、かつ任意選択で、S103A、G159D、Q236H、Q245R、N248D及びN252Kからなる群から選択される少なくとも1つの変異を含み、このプロテアーゼ変異体のアミノ酸位置は、このプロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体を提供する。
するのに好適な条件下で培養して、少なくとも1種のサブチリシン変異体を生産する工程、を含む、方法を提供する。一部の実施形態では、この方法は、生産されたサブチリシン変異体を回収する工程を更に含む。一部の更なる実施形態では、発現ベクター中の核酸は制御可能なようにプロモーターに連結されている。一部の更なる実施形態では、発現ベクター中の核酸は制御可能なようにプロモーターに連結されている。本発明はまた、本明細書で提供される発現ベクターを含む、宿主細胞を提供する。一部の実施形態では、宿主細胞はバチルス宿主細胞である。一部の更なる実施形態では、宿主細胞は、B.サブチリス宿主細胞である。
分に含まれる活性な酵素の濃度を測定するという用途が見出されている。このアッセイは、可溶性の合成基質、スクシニル−アラニン−アラニン−プロリン−フェニルアラニン−p−ニトロアニリド(suc−AAPF−pNA)を酵素が加水分解した際に放出されるp−ニトロアニリンの放出速度を測定する。加水分解反応により黄色味が生じる速度を分光光度計で410nmにて測定する。この速度は活性酵素濃度に比例する。加えて、280ナノメートル(nm)での吸光度測定を使用して、総タンパク質濃度を測定することもできる。活性酵素/総タンパク質比は酵素の純度も与える。
包含される。
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け落ち込んだ場合、累積スコアが0以下になった場合、又はいずれかの配列が末端に達した場合に停止される。BLASTアルゴリズムパラメーターW、T、及びXは、アライメントの感度及び速度を決定する。BLASTプログラムは、ワード長(W)11、BLOSUM62スコア行列(Henikoff及びHenikoff、Proc.Natl.Acad.Sci.USA 89:10915[1992]を参照されたい):アライメント(B)50、期待値(E)10、M’5、N’−4、及び両方のストランドの比較をデフォルトとして使用する。
、約80%、約85%、約90%、約91%、約92%、約93%、約94%、約95%、約96%、約97%、約98、約99%、又は約99.5%以上(モルベースで)を構成する。
び/又は野生型酵素と比較した場合に、一定時間経過後のタンパク質分解活性がより高く維持されていることを意味する。
漂白添加剤及び「染み抜き剤」又は前処理型ののクリーニング助剤;が挙げられる。一部の実施形態では、顆粒状組成物は「コンパクト」形態であり;一部の実施形態では、液体組成物は「濃縮された」形態である。
配列中の1つ以上の核酸(又はコドン)を切断又は1箇所以上でトランケーションさせて、サイレントではない変化を生じさせるよう、複数の変化を加えることもできる。核酸配列における多くのこのような変更は、得られる配列にコードされる変異体プロテアーゼの酵素活性を、元の核酸配列によりコードされている変異体プロテアーゼのものと比較して実質的に変化させなくてよい。同様に、発現系(例えば、細菌による発現系)で最適な発現をもたらすコドンが1つ以上包含されるように、必要に応じて、上記1つ以上のコドンには同一のアミノ酸をコードさせたまま、本発明の核酸を改変させてもよい。
1S、X251R、X252I、X252F、X252H、X252R、X253F、X253I、X253R、X254C、X256N、X258R、X260V、X260I、X262H、X262D、X263F、X265F、X267N、X267V、X267M、X269I、X269R、X270C、X271F、X271V、X271I、X271P、X271H、X271M、X271T、X271L、X271A、X272F、X272R、X272F、X273I、X273F、及びX274Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、ポリペプチドを提供する。
たサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020R−X−43R、X020K−X062E、X024F−X116L、X020K−X024F、X024R−X174T、X024R−X118R、X024R−X235F、X024R−X086R、X024R−X086W、X078R−X118R、X033S−X118R、X033S−X235F、X209A−X241R、X020R−X076D、X018R−X245R、X024R−X045T、X232V−X245R、X118R−X172V、X118R−X194T、X008T−X024R、X235F−X243F、X018R−X103A、X018R−X104I、X086W−X118R、X086W−X243F、X086W−X209A、X024C−X033S、X024R−X232V、X024R−X243F、X024R−X239Q、X024R−X101G、X024R−X141G、X024R−X033S、X024R−X274I、X024R−X209A、X078R−X086W、X101G−X232V、X033S−X148F、X033S−X086W、X033S−X201S、X033S−X078R、X033S−X241R、X033S−X209A、X230E−X249R、X232V−X249R、X118R−X235F、X076D−X245R、X086W−X235F、X024R−X247H、X024R−X104A、X078R−X235F、X101G−X249R、X103A−X232V、X033S−X048T、X033S−X239T、X033S−X253A、X143A−X209A、X209A−X235F、X018R−X045T、X209A−X243F、X024R−X272P、X024R−X269C、X101G−X104I、X104I−X232V、X076D−X249R、及びX024R−X076Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−X045T−X076D−X249R、X018R−X043D−X045T−X076D−X242R−X249R、X024R−X043D−X242R−X249R、X018R−X020R−X024R−X043D−X045T−X242R、X020R−X024R−X043R−X076D、X018R−X020R−X043D−X045T−X230E−X242R、X020R−X024R−X043R−X045T−X076D−X242R−X249R、X018R−X043R−X045T−X076D−X242R、X018R−X020R−X043R−X076D−X230E−X242R、X018R−X024R−X043D−X249R、X018R−X024R−X043R−X045T−X230E−X249R、X018R−X020R−X043R−X045T−X076D−X249R、X018R−X024R−X242R、X018R−X043R−X045T−X076D−X230E−X242R、X045T−X242R−X249R、X018R−X024R−X043D−X242R、X018R−X020R−X043D−X045T−X240P、X024R−X043R−X045T−X242R−X249R、X018R−X024R−X30S−X31S−X32I−X33Q−X34V−X35F、X018R−X020R−X043R−X076D、X020R−X043D−X045T−X076D−X242R−X249R、X018R−X024R−X043D−X230E−X242R、X018R−X024R−X043D−X242R−X249R、X024R−X043D−X045T−X242R−X249R、X043R−X230E−X249R、X024R−X043R−X076D−X230E−X249R、X020R−X024R−X043D−X076D−X249R、X024R−X045T−X242R−X273V、X020R−X024R−X045T−X076D−X242R−X249R、X018R−X024R−X043D−X076D−X242R、X018R−X043R−X076D−X230E−X249R、X018R−X020R−X043R−X045T−X249R、X018R−X043R−X045T−X230E−X242R、X020R−X024R−X043D−X045T−X230E−X242R、X018R−X043D−X230E−X249R、X018R−X043R−X076D−X242R、X018R−X020R−X076D、X018R−X020R−X043D−X076D−X242R−X249R、X020R−X024R−X043D−X076D−X242R−X249R、X043D−X242R−X249R、X018R−X020R−X024R−X043R−X076D、X018R−X020R−X043D−X045T−X076D−X249R、X018R−X020R−X043R−X045T−X076D−X230E−X249R、X018R−X076D−X242R、X020R−X043R−X249R、X018R−X076D−X242R−X249R、X018R−X024R−X045T−X230E−X249R、X230E−X249R、X018R−X045T−X249R、X020R−X043R−X076D、X043R−X045T−X249R、X018R−X043D−X076D−X242R−X249R、X043R−X076D−X249R、X018R−X045T、X020R−X076D−X230E−X242R、X020R−X024R−X043D−X045T、X024R−X043D−X076D−X242R−X249R、X020R−X045T−X249R、X043R−X076D−X153A−X249R、X043R−X076D−X230E−X249R、X018R−X043D−X076D−X249R、及びX020R−X043R−X076D−X227Iから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
45R−X248D、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X159E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024K−X101G−X103A−X104I−X128N−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X148I−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X148I−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、及びX101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、及びX024R−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−X194F−X211Q、X020R−X024R−X052N−X059A−X216F、X024R−X167W−X224A−X249R、X057R−X167W−X249R、X025R−X103N−X186K−X194F−X224A、X105T−X128N−X144R−X148I−X212M、X020R−X059A−X144R−X192W−X224A、X024R−X043A−X117F−X194F−X211Q、X117F−X194F−X213A−X270C、X078R−X091F−X121F−X233C−X252R、X057R−X099F−X105T−X198L−X213A、X023A−X091F−X101A−X198L−X252R、X062Q−X103N−X121F−X144R−X249R、X043R−X101G−X103A−X104I−X232V−X242R−X245R、X023A−X024R−X117F−X212M−X216F、X104L−X213A−X216F、X194F−X211Q−X236N、X062Q−X103N−X117F−X194F、X024R−X062Q−X104L−X106G−X249R、X057R−X089I−X198L、X046R−X059A−X106G−X217E−X249R、X117F−X213A−X215F、X101A−X120F−X192W−X215F−X224A、X043A−X057R−X117F−X144R−X183D、X046R−X183D−X238L、X025R−X043A−X089I−X117F、X078R−X104L−X213A−X215F−X224A、X091F−X099F−X101A−X105T−X167W、X106G−X117F−X238L、X046R−X089I−X091F−X101A−X116A、X020R−X062Q−X089I−X186K−X212M、X057R−X099F−X121F−X185I−X192W、X046R−X089I−X192W−X233C−X270C、X089I−X117F−X185I−X215F−X233C、X052N−X104L−X183D−X216F−X249R、X078R−X099F−X116A−X186K−X224A、X025R−X105T−X128N−X144R−X270C、X105T−X211Q−X216F、X024R−X046R−X091F−X121F、X106G−X185I−X216F−X236N、X062Q−X101A−X236N−X252R−X270C、X025R−X043A−X091F−X198L−X270C、X020R−X023A−X104L−X192W−X233C、X024R−X043A−X105T−X106G−X198L、X020R−X089I−X217E、X024R−X091F−X198L−X215F−X239S、X046R−X089I−X099F−X186K−X212M、X104L−X120F−X186K−X216F−X252R、X022W−X194F−X213A−X233C−X238L、X099F−X105T−X106G−X194F−X212M、X089I−X105T−X116A−X215F−X216F、X025R−X116A−X120F−X224A−X270C、X043A−X059A−X101A−X216F−X224A、X057R−X183D−X236N、X025R−X062Q−X128N−X144R−X185I、X103N−X120F−X167W−X198L−X233C、X022W−X089I−X216F、X024R−X106G−X116A−X212M−X224A、X020R−X052N−X101A−X198L−X233C、X089I−X091F−X185I−X211Q−X270C、X111I−X215F−X239S、X024R−X116A−X186K−X233C−X236N、及びX023A−X103N−X106G−X212M−X215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
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20R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R−X275S、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X024R−X076D、X018R−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X076D−X104I−X232V−X249R、X018R−X076D−X103A−X232V、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X175E−X183D−X211Q−X215F−X249R、X018R−X020R−X043D−X078R−X101G−X103A−X104I−X217E−X232V−X245R−X273E、X020R−X024R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X005S−X101G−X103A−X104I−X232V−X245R−X249R、X103A−X104I−X232V、X018R−X020R−X024R−X068A−X076D−X101A−X116A−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X198L−X215F−X249R−X275S、X018R−X024R−X076D−X183D−X198L−X211Q−X213A−X249R、及びX043D−X045T−X101G−X103A−X104I−X232V−X245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−X158E−X188D−X217E−X232V−X245R−X248D−X249R−X271F、X076D−X101G−X103A−X104I−X114V−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X024R−X076D−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X024R−X043R−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X043R−X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101A−X103A−X104I−X158E−X166D−X188D−X217E−X232V−X245R−X248D−X249R、X076D−X101G−X103A−X104I−X128L−X158E−X188D−X232V−X245R−X248D−X249R−X271F、及びX043R−X076D−X101G−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
13A、X078N−X104L−X118R−X128D、X102A−X103N−X105T−X194E、X022L−X078N−X128D−X213A、X027R−X100S−X118R−X160D−X188D−X243F、X024F−X102A−X186K−X213A−X217E−X243F、X033S−X105T−X188D−X216F、X023A−X100S−X194E−X212M、X048R−X128D−X185E−X239G、X020K−X024F−X033S−X129E−X194E、X020K−X027R−X129E−X166D−X239G、X022L−X023A−X027R−X101D−X104L−X216F、X033S−X118R−X129E−X194E−X239G、X022L−X078N−X116L−X129E−X256N、X027R−X101D−X103N−X105T−X272F、X048R−X078N−X116L−X185E−X217E−X239G、X023A−X024F−X027R−X062E、X024F−X103N−X104L−X118R−X188D、X026F−X104L−X256N−X272F、X024F−X043W−X104L−X121F−X129E、X062E−X078N−X116L−X224A、X023A−X024F−X051W−X158E、X027R−X038F−X102A−X116L、X062E−X078N−X144R−X212M、X031F−X116L−X256N−X272F、X022L−X033S−X104L−X116L−X160D−X186K、X024F−X118R−X129E−X186K−X213A、X043W−X105T−X213A−X215D−X216F、X031F−X105T−X186K−X188D、X026F−X194E−X213A−X256N、及びX103N−X160D−X250I−X256Nから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−X188D−X232V−X245R−X248D、X022A−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D−X271F、X024F−X062E−X116L−X188D、X022A−X024R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D、X023A−X062E−X116L−X188D、X043W−X062E−X116L、X020K−X023A−X116L−X188D、X043W−X062E−X116L−X188D、X024F−X062E−X116L、X062E−X116L−X188D、及びX022A−X024R−X103A−X104I−X128I−X159D−X188D−X232V−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
させて番号付けされる、サブチリシン変異体を提供する。
X103A−X104I−X159D−X232V−X245R−X248D−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、ポリペプチドを提供する。
69R、V004R−N269R、L082R−N269R、N018R−N043R、G020R−N043R、V004R−N043R、T022R−N043R、S009A−N043R、A001R−N043R、S024R−N043R、S009A−N018R、V004R−N018R、A001R−N018R、S024R−L082R、S009A−L082R、N018R−L082R、A001R−L082R、S078R−L082R、G020R−L082R、T022R−L082R、V004R−L082R、N043R−L082R、N043R−H249R、G020R−H249R、V004R−H249R、N018R−H249R、S009A−H249R、S212F−H249R、T022R−H249R、S024R−H249R、G115R−H249R、A001R−H249R、L082R−H249R、S242R−H249R、W241R−H249R、V244R−H249R、S078R−H249R、N018R−G115R、G020R−G115R、T022R−G115R、S078R−G115R、S009A−G115R、V004R−G115R、A001R−G115R、L082R−G115R、N043R−G115R、S024R−G115R、S009A−G020R、N018R−G020R、V004R−G020R、A001R−G020R、S009A−E271L、G020R−E271L、S024R−E271L、V244R−E271L、W241R−E271L、N043R−E271L、T022R−E271L、H249R−E271L、S212F−E271L、G115R−E271L、S242R−E271L、S078R−E271L、V004R−E271L、N269R−E271L、A001R−E271L、N018R−E271L、及びL082R−E271Lから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、ポリペプチドを提供する。
解活性を有する成熟型であり、かつG020R−N043R、G020K−N062E、S024F−N116L、G020K−S024F、S024R−A174T、S024R−G118R、S024R−K235F、S024R−P086R、S024R−P086W、S078R−G118R、T033S−G118R、T033S−K235F、Y209A−W241R、G020R−N076D、N018R−Q245R、S024R−R045T、A232V−Q245R、G118R−A172V、G118R−A194T、I008T−S024R、K235F−N243F、N018R−S103A、N018R−V104I、P086W−G118R、P086W−N243F、P086W−Y209A、S024C−T033S、S024R−A232V、S024R−N243F、S024R−P239Q、S024R−S101G、S024R−S141G、S024R−T033S、S024R−T274I、S024R−Y209A、S078R−P086W、S101G−A232V、T033S−L148F、T033S−P086W、T033S−P201S、T033S−S078R、T033S−W241R、T033S−Y209A、A230E−H249R、A232V−H249R、G118R−K235F、N076D−Q245R、P086W−K235F、S024R−R247H、S024R−V104A、S078R−K235F、S101G−H249R、S103A−A232V、T033S−A048T、T033S−P239T、T033S−T253A、T143A−Y209A、Y209A−K235F、N018R−R045T、Y209A−N243F、S024R−A272P、S024R−R269C、S101G−V104I、V104I−A232V、N076D−H249R、及びS024R−N076Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
18R−N043D−R045T−N076D−S242R−H249R、S024R−N043D−S242R−H249R、N018R−G020R−S024R−N043D−R045T−S242R、G020R−S024R−N043R−N076D、N018R−G020R−N043D−R045T−A230E−S242R、G020R−S024R−N043R−R045T−N076D−S242R−H249R、N018R−N043R−R045T−N076D−S242R、N018R−G020R−N043R−N076D−A230E−S242R、N018R−S024R−N043D−H249R、N018R−S024R−N043R−R045T−A230E−H249R、N018R−G020R−N043R−R045T−N076D−H249R、N018R−S024R−S242R、N018R−N043R−R045T−N076D−A230E−S242R、R045T−S242R−H249R、N018R−S024R−N043D−S242R、N018R−G020R−N043D−R045T−S240P、S024R−N043R−R045T−S242R−H249R、N018R−S024R−V30S−L31S−D32I−T33Q−G34V−I35F、N018R−G020R−N043R−N076D、G020R−N043D−R045T−N076D−S242R−H249R、N018R−S024R−N043D−A230E−S242R、N018R−S024R−N043D−S242R−H249R、S024R−N043D−R045T−S242R−H249R、N043R−A230E−H249R、S024R−N043R−N076D−A230E−H249R、G020R−S024R−N043D−N076D−H249R、S024R−R045T−S242R−A273V、G020R−S024R−R045T−N076D−S242R−H249R、N018R−S024R−N043D−N076D−S242R、N018R−N043R−N076D−A230E−H249R、N018R−G020R−N043R−R045T−H249R、N018R−N043R−R045T−A230E−S242R、G020R−S024R−N043D−R045T−A230E−S242R、N018R−N043D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−G020R−N076D、N018R−G020R−N043D−N076D−S242R−H249R、G020R−S024R−N043D−N076D−S242R−H249R、N043D−S242R−H249R、N018R−G020R−S024R−N043R−N076D、N018R−G020R−N043D−R045T−N076D−H249R、N018R−G020R−N043R−R045T−N076D−A230E−H249R、N018R−N076D−S242R、G020R−N043R−H249R、N018R−N076D−S242R−H249R、N018R−S024R−R045T−A230E−H249R、A230E−H249R、N018R−R045T−H249R、G020R−N043R−N076D、N043R−R045T−H249R、N018R−N043D−N076D−S242R−H249R、N043R−N076D−H249R、N018R−R045T、G020R−N076D−A230E−S242R、G020R−S024R−N043D−R045T、S024R−N043D−N076D−S242R−H249R、G020R−R045T−H249R、N043R−N076D−S153A−H249R、N043R−N076D−A230E−H249R、N018R−N043D−N076D−H249R、及びG020R−N043R−N076D−V227Iから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、及びS101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
48D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、及びS024R−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
24R−P052N−Q059A−S216F、S024R−Y167W−T224A−H249R、T057R−Y167W−H249R、G025R−S103N−R186K−A194F−T224A、S105T−S128N−S144R−L148I−S212M、G020R−Q059A−S144R−Y192W−T224A、S024R−N043A−N117F−A194F−G211Q、N117F−A194F−T213A−A270C、S078R−Y091F−V121F−L233C−N252R、T057R−S099F−S105T−I198L−T213A、G023A−Y091F−S101A−I198L−N252R、N062Q−S103N−V121F−S144R−H249R、N043R−S101G−S103A−V104I−A232V−S242R−Q245R、G023A−S024R−N117F−S212M−S216F、V104L−T213A−S216F、A194F−G211Q−Q236N、N062Q−S103N−N117F−A194F、S024R−N062Q−V104L−S106G−H249R、T057R−E089I−I198L、G046R−Q059A−S106G−L217E−H249R、N117F−T213A−A215F、S101A−H120F−Y192W−A215F−T224A、N043A−T057R−N117F−S144R−N183D、G046R−N183D−N238L、G025R−N043A−E089I−N117F、S078R−V104L−T213A−A215F−T224A、Y091F−S099F−S101A−S105T−Y167W、S106G−N117F−N238L、G046R−E089I−Y091F−S101A−N116A、G020R−N062Q−E089I−R186K−S212M、T057R−S099F−V121F−N185I−Y192W、G046R−E089I−Y192W−L233C−A270C、E089I−N117F−N185I−A215F−L233C、P052N−V104L−N183D−S216F−H249R、S078R−S099F−N116A−R186K−T224A、G025R−S105T−S128N−S144R−A270C、S105T−G211Q−S216F、S024R−G046R−Y091F−V121F、S106G−N185I−S216F−Q236N、N062Q−S101A−Q236N−N252R−A270C、G025R−N043A−Y091F−I198L−A270C、G020R−G023A−V104L−Y192W−L233C、S024R−N043A−S105T−S106G−I198L、G020R−E089I−L217E、S024R−Y091F−I198L−A215F−P239S、G046R−E089I−S099F−R186K−S212M、V104L−H120F−R186K−S216F−N252R、T022W−A194F−T213A−L233C−N238L、S099F−S105T−S106G−A194F−S212M、E089I−S105T−N116A−A215F−S216F、G025R−N116A−H120F−T224A−A270C、N043A−Q059A−S101A−S216F−T224A、T057R−N183D−Q236N、G025R−N062Q−S128N−S144R−N185I、S103N−H120F−Y167W−I198L−L233C、T022W−E089I−S216F、S024R−S106G−N116A−S212M−T224A、G020R−P052N−S101A−I198L−L233C、E089I−Y091F−N185I−G211Q−A270C、L111I−A215F−P239S、S024R−N116A−R186K−L233C−Q236N、及びG023A−S103N−S106G−S212M−A215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−S024R−S101G−V104I、G020R−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−Q245R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−N076D−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、A001T−N018R−S024R−N076D−N116A−T213A−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、N018R−S024R−N076D−T213A−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、G020R−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S101G−S103A−V104I、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−S103A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−G211Q−H249R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−S024R−N076D−A232V−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−Q245R、S024R−V104I−Q245R、S101G−A232V、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、S024R−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、S024R−S101G−V104I−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−V104I、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−T213A−H249R、S024R−V104I−H249R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−N076D−S103A−V104I−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q245R−E271G、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S10
1G−S103A−V104I−A232V−Q245R−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、S024R−S103A−M175L−A232V−H249R、N018R−S024R−N076D−N116A−T213A−H249R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−A232V、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、S024R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、S101G−S103A−V104I−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S103A−A232V、N018R−S024R−N076D−S101A−G211Q−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101G−A232V、A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、S024R−N076D−S103A−V104I−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S103A−V104I−A232V、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、S024R−N076D−V104I−Q245R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−N076D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N
018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、N018R−S024R−N076D−N116A−H249R、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−S101G−Q245R、S024R−N076D−S101G−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、S024R−S101G、N018R−T22W−S024R−N076D−T213A−A215F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−V104I、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S024R−N076D−Q245R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N018R−S103A、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−V104I、S101G−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S103A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、S101G−H249R、S024R−N076D−S101G−S103A−V104I−M175L−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N01
8R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S103A−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−A232V、S024R−S103A−V104I、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−S103A−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、S103A−V104I−Q245R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、A016T−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101G、N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−A215F−H249R、N018R−V104I−A232V、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S101G−A232V−H249R、S103A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S024R−N076D−S103A−V104I−H249R、S024R−S101G−S103A−V104I、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N018R−N076D−A232V−H249R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、A232V−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N076D−V104I−Q245R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、S024R−S101G−S103A−A232V、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、S103A−A232V−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、S024R−S103A−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−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A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R
−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N076D−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−Q245R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N076D−V104I−A232V−Q245R、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N076D−S101G−S103A−V104I−A232V−H249R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、N076D−S101G−S103A−V104I−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、S024R−N076D−S101G、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−N076D−S101G−I198T−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−N076D−V104I−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N0
76D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−V104I、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A
−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、及びN043D−R045T−S101G−S103A−V104I−A232V−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
32V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A114V−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−N076D−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−N043R−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101A−S103A−V104I−A158E−S166D−S188D−L217E−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、及びN043R−N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
−S128D、G102A−S103N−S105T−A194E、T022L−S078N−S128D−T213A、K027R−G100S−G118R−S160D−S188D−N243F、S024F−G102A−R186K−T213A−L217E−N243F、T033S−S105T−S188D−S216F、G023A−G100S−A194E−S212M、A048R−S128D−N185E−P239G、G020K−S024F−T033S−P129E−A194E、G020K−K027R−P129E−S166D−P239G、T022L−G023A−K027R−S101D−V104L−S216F、T033S−G118R−P129E−A194E−P239G、T022L−S078N−N116L−P129E−S256N、K027R−S101D−S103N−S105T−A272F、A048R−S078N−N116L−N185E−L217E−P239G、G023A−S024F−K027R−N062E、S024F−S103N−V104L−G118R−S188D、V026F−V104L−S256N−A272F、S024F−N043W−V104L−V121F−P129E、N062E−S078N−N116L−T224A、G023A−S024F−V051W−A158E、K027R−T038F−G102A−N116L、N062E−S078N−S144R−S212M、L031F−N116L−S256N−A272F、T022L−T033S−V104L−N116L−S160D−R186K、S024F−G118R−P129E−R186K−T213A、N043W−S105T−T213A−A215D−S216F、L031F−S105T−R186K−S188D、V026F−A194E−T213A−S256N、及びS103N−S160D−L250I−S256Nから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
48D、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D−E271F、S024F−N062E−N116L−S188D、T022A−S024R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、G023A−N062E−N116L−S188D、N043W−N062E−N116L、G020K−G023A−N116L−S188D、N043W−N062E−N116L−S188D、S024F−N062E−N116L、N062E−N116L−S188D、及びT022A−S024R−S103A−V104I−S128I−G159D−S188D−A232V−N248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
128I−P129E−G159D、S024F−N062E−N116L−S188D、S024R−S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101D−S103N−N116L−S144R−A215D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N043R−S101G−S103A−V104I−G159D−S188D−L217E−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−S128I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−S101G−S103A−V104I−G159D−L217E−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022L−T038F−A048R−N062E−G100S−R186K、T033S−N043W−N218D−P239G−N243F、V026F−A048R−S105T−T213A−N218D−T224A、V026F−L031F−S078N−G102A−S160D、V026F−V051W−V104L−S106E、V104L−S105T−T213A−L217E−S256N、A016S−N062E−A158E−H249R、A016S−N062E−A158E−R186H−E271F、A016S−N062E−A158E−R186H−H249R、A016S−N062E−V104L−A158E−R186H−E271F、A016S−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、G020K−G023A−N062E−S188D、G020K−G023A−S024F−N062E−G118R−S188D−T213A、G020K−N043W−N062E−N116L−S188D−T213A−P239G、G020K−S024F−N062E−S188D−P239G、G023A−N062E−N116L−G118R、G023A−N062E−N116L−G118R−S188D−P239G、G023A−S024F−N062E−N116L−G118R、H017R−T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N062E−A158E−G159E−H249R、N062E−A158E−H249R、N062E−A158E−R186H−E271F、N062E−A158E−R186H−H249R、N062E−A158E−R186H−H249R−E271F、N062E−A158E−S188D−H249R、N062E−A158E−S188D−H249R−E271F、N062E−G159E−H249R、N062E−G159E−H249R−E271F、N062E−G159E−R186H−H249R、N062E−G159E−S188D−H249R、N062E−R186H−S188D−H249R−E271F、N062E−S101A−A158E−H249R、N062E−S101A−A158E−R186H−E271F、N062E−S101A−A158E−R186H−H249R−E271F、N062E−S101A−G159E−H249R、N062E−S101A−R186H−H249R、N062E−S101A−S188D−H249R、N062E−S101A−S188D−H249R−E271F、N062E−S101A−V104L−A158E−R186H−E271F、N062E−S128N−A158E−G159E−E271F、N062E−V104L−A158E−S188D−H249R−E271F、N076D−S101G−S103A−V104I−A232V−M222Q−Q245R、S024F−N062E−N116L−P239G、S024F−N062E−S188D−T213A、S024F−N116L、S024R−N043R−N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F−E271F、S101A−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S128N−A158E−R186H−E271F、S101A−S128N−A158E−Y209E−H249R、S101A−V104L−A158E−R186H−S188D−H249R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222Q−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A232V−M222Q−Q245R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104I−A158E−S188
D−A232V−Q245R−N248D−H249R、S101S−S103G−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、S128N−A158E−G159E−E271F、S128N−A158E−H249R、S128N−A158E−R186H−E271F、S128N−A158E−R186H−H249R、S128N−A158E−R186H−S188D−E271F、S128N−A158E−S188D−E271F、S128N−A158E−S188D−H249R、S128N−A158E−S188D−Y209E−E271F、S128N−A158E−Y209E−、T022A−N043R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N062E−A158E、T022A−S024R−S101D−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S024R−S103A−V104I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S128N−A158E−H249R、V104L−S128N−A158E−H249R、V104L−S128N−A158E−R186H−E271F、V104L−S128N−A158E−R186H−H249R、及び/又はV104L−S128N−A158E−S188D−H249R; b)A016S−N062E−A158E−H249R−E271F、A016S−N062E−S128N−R186H−E271F、A016S−N062E−V104L−R186H−S188D−E271F、A016S−S101A−S128N−R186H、A016S−S128N−A158E−R186H、A016S−V104L−A158E−R186H−E271F、A016S−V104L−S188D−H249R、A158E−R186H−H249R、A158E−R186H−S188D−H249R−E271F、G020K−G023A−N116L−S188D、G020K−G023A−S024F−N062E−N116L−S188D−T213A、G020K−N043W−N062E−N116L−P239G、G020K−S024F−N043W−N062E−N116L−T213A、G020K−S024F−N062E、G023A−N043W−N062E−N116L−G118R−T213A、G023A−T038F−S078N−G100S−S212M−A215D、G100S−N116L−A158E−T213A、G102A−S103N−S105T−A194E、H017R−T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、N043W−N062E−N116L−S188D、N062E−A158E−H249R−E271F、N062E−A158E−R186H−S188D−H249R、N062E−L148I−G159E、N062E−N116L−S188D、N062E−R186H−H249R、N062E−S078N−G102A−N116L−S144R−L250I、N062E−S101A−A158E−R186H−H249R、N062E−S101A−A158E−S188D−H249R、N062E−S101A−R186H、N062E−S101A−R186H−E271F、N062E−S101A−R186H−H249R−E271F、N062E−S101A−R186H−S188D−E271F、N062E−S101A−R186H−S188D−H249R、N062E−S101A−V104L−R186H−S188D−E271F、N062E−S128N−A158E、N062E−S128N−G159E−H249R、N062E−S188D−P239G、N062E−V104L−G159E−H249R、N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A114V−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A232V−M222S−Q245R、S024F−A048R−G118R−S166D−L217E、S024F−N062E−N116L、S024F−N062E−N116L−T213A−P239G、S024F−N062E−S188D−P239G、S024F−S101D−G118R−A215D−L250I−A272F、S024R−K027R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248
D−H249R、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、S078N−V104L−G118R−S128D、S101A−A158E−R186H−H249R、S101A−A158E−R186H−S188D−H249R、S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、S101A−S103G−A158E−R186H−H249R、S101A−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−G159E−A232V−Q245R−N248D−H249R、S101A−S128N−A158E−H249R、S101A−S128N−A158E−S188D−Y209E−E271F、S101A−S128N−A158E−Y209E、S101A−S128N−P129E−R186H−H249R、S101A−V104L−A158E−R186H−H249R、S101A−V104L−A158E−R186H−S188D−E271F、S101A−V104L−S128N−A158E−R186H−E271F、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−A232V−M222S−Q245R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−S130A−A158E−N183D−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101S−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N043R−N062E−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−N043R−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S024R−N043R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S024R−S101D−S103A−V104I−G118R−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S101A−A158E−R186H−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D、T022A−S103A−V104I−G159D−S188D−A232V−N248D、T022L−L031F−G102A−S128D−T224A−N243F、T022L−T038F−V121F−S160D−A272F、V026F−S078N−G159C−R186K−N243F、V104L−A158E−H249R、V104L−A158E−R186H−H249R、V104L−A158E−R186H−H249R−E271F、V104L−A158E−R186H−S188D−H249R、V104L−A158E−R186H−S188D−H249R−E271F、V104L−A158E−S188D−H249R−E271F、V104L−S128N−A158E−R186H−S188D−E271F、V104L−S128N−G159E−E271F、V104L−S128N−R186H−S188D−H249R、及び/又はV121F−N185E−T224A−P239G; c)A016S−S128N−R186H−E271F、N076D−S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R−E271G、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−G102A−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F
、A016S−A158E−H249R、A016S−A158E−H249R−E271F、A016S−A158E−R186H−H249R、A016S−L111V−S188D−、A016S−T022A−A158E−R186H−E271F、A048R−S078N−N116L−N185E−L217E−P239G、A048R−S128D−N185E−P239G、A158E−R186H−H249R−E271F、E089P−S101A−P129E−R186H、G020K−G023A−N043W−N116L−S188D−T213A−P239G、G020K−G023A−N062E−N116L−G118R−T213A、G020K−G023A−S024F−N062E−S188D−T213A−P239G、G020K−K027R−P129E−S166D−P239G、G020K−S024F−N062E−P239G、G020K−S024F−T033S−P129E−A194E、G023A−G100S−A194E−S212M、G023A−N043W−N116L−G118R−S188D、G023A−S024F−G118R−S188D−P239G、G023A−S024F−K027R−N062E、G023A−S024F−N043W−N062E−N116L−G118R、G023A−S024F−N116L−G118R−S188D−T213A、G023A−S024F−N116L−S188D−P239G、K027R−G100S−G118R−S160D−S188D−N243F、K027R−S101D−S103N−S105T−A272F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、N062E−S078N−N116L−T224A、N062E−V104L−A158E−R186H−S188D−H249R、N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S024F−G102A−R186K−T213A−L217E−N243F、S024F−N043W−G118R−S188D、S024F−N043W−V104L−V121F−P129E、S024F−N116L−G118R−S188D−P239G、S024F−S103N−V104L−G118R−S188D、S024R−N043R−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−N076D−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101A−L111V−P129E、S101A−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−V104L−S128N−A158E−R186H、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S128N−P129E−R186H、T022A−A158E−R186H−H249R−E271F、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S103A−V104I−S128I−G159D−S188D−A232V−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S128N−A158E−R186H、T022A−S128N−R186H−S188D−、T022A−V104L−A158E−H249R、T022A−V104L−R186H−S188D−H249R、T022L−G023A−K027R−S101D−V104L−S216F、T022L−S078N−N116L−P129E−S256N、T022L−S078N−S128D−T213A、T033S−G118R−P129E−A194E−P239G、T033S−S105T−S188D−S216F、V026F−V104L−S256N−A272F、T022A−N043R−S103A−V104I−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S101D−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、及び/又はT022A−S103A−V104I−S128I−P129E−G159D−S188D−A232V−N248D−E271F; d)G118R−Y209A、G118R−Y209A−N243F、L021M−S024R−T033S、P005S−S078R−G118R−W241R、P086W−G118R−A133V、P086W−G118R−N243F、P086W−G118R−Y209A、P086W−Y209A−N243F、S024R−A174T、S024R−G118R、S024R−G118R−Y209A、S024R−G118R−Y209A−K235F、S024R−G118R−Y209A−N243F、S024R−K235F、S024R−P086R、S024R−P086S−S141G、S024R−P086W、S024R−P086W−G118R、S024R−P086W−G118R−V203I、S024R−P086W−N243F、S024R−P086W−Y209A、S024R−S078R−P086W、S024R−S078R−P086W−G118R−A270T、S024R−S078R−P086W−N243F、S024R−T033S−A133V、S024R−T033S−G118R、S024R−T033S−P086S−S085N−K235F、S024R−T033S−P086S−S087N−Y209A、S024R−T033S−P086W、S024R−T033S−P086W−G118R、S024R−T033S−S078R−P086W、S024R−T033S−S078R−P086W−G118R、S024R−T033S−S078R−Y209A、S024R−T033S−W241R、S024R−T033S−Y209A−K235F、S024R−Y209A−W241R、S078R−G118R、S078R−P086W−K235F、S078R−P086W−N243F、S078R−P086W−Y209A、S078R−Y209A−K235F、T033S−A172V−Y209A、T033S−G118R、T033S−G118R−G159D−Y209A、T033S−G118R−N243F、T033S−G118R−W241R、T033S−G118R−Y209A−N243F、T033S−K235F、T033S−P086W−G118R、T033S−P086W−G118R−Y209A−N243F、T033S−P086W−N243F、T033S−S078R−P086W、T033S−S078R−P086W−G118R−Y209A、T033S−S078R−Y209A、T033S−Y209A−N243F、Y209A−W241R、A001R−S009A−N043R、A001R−S101G−S103A−V104I−A232V−Q245R、A001T−N018R−S024R−N076D−N116A−T213A−H249R、A194F−G211Q−Q236N、E089I−N116A−N117F−T224A−H249R、G020R−G025R−N116A−Y167W、G020R−H249R−N269R、G020R−N043D−N076D−A230E−H249R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043R−A230E、G020R−N043R−A230E−S242R、G020R−N043R−E271L、G020R−N043R−H249R、G020R−N043R−H249R−E271L、G020R−N043R−N269R、G020R−N043R−R045T−A230E、G020R−N043R−R045T−S101A−N269R、G020R−N043R−R045T−S242R、G020R−N043R−S101A−N116A−T213A−A215F、G020R−N043R−S101A−N269R、G020R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−N043R−S212F、G020R−N043R−S212F−W241R、G020R−N043R−S242R、G020R−N043R−S242R−E271L、G020R−N043R−S242R−H249R、G020R−N043R−V244R、G020R−N043R−W241R、G020R−N062Q−E089I−R186K−S212M、G020R−N076D、G020R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N116A−N269R、G020R−P052N−N062Q−Y091F−Y192W、G020R−Q059A−S144R−Y192W−T224A、G020R−S024
R−K27E−N043R−N076D−A230E、G020R−S024R−N043D−H249R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−N043D−S242R、G020R−S024R−N043R−R045T、G020R−S024R−N043R−R045T−H249R、G020R−S024R−N043R−R045T−N116A、G020R−S024R−N043R−R045T−N116A−T213A、G020R−S024R−N043R−R045T−S101A−N269R、G020R−S024R−N043R−R045T−S101A−T213A、G020R−S024R−N043R−S242R、G020R−S024R−N076D−H249R、G020R−S024R−N116A、G020R−S024R−N116A−A215F、G020R−S024R−N116A−T213A、G020R−S024R−N116A−T213A−A215F、G020R−S024R−P052N−Q059A−S216F、G020R−S024R−R045T−A230E−S242R、G020R−S024R−R045T−N116A−N269R、G020R−S024R−R045T−N269R、G020R−S024R−S101A−A215F、G020R−S024R−S101A−N116A、G020R−S024R−S101G−S103A−V104I−L217E−A232V−Q245R−H249R、G020R−S024R−S242R−H249R、G020R−S024R−T213A、G020R−S024R−T213A−A215F、G020R−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S078R−S101G−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S087D−S101G−S103A−V104I−A232V−Q245R、G020R−S101A−N116A−N269R、G020R−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−G118R−A232V−Q245R、G020R−S101A−S103A−V104L−A232V−Q245R、G020R−S101A−S103A−V104V−A232V−Q245R、G020R−S101A−S103S−V104I−A232V−Q245R、G020R−S101A−S103S−V104V−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、G020R−S101G−S103A−A232V−Q245R、G020R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−V150L−A232V−Q245R、G020R−S101G−S103A−V104L−A232V−Q245R、G020R−S101G−S103A−V104V−A232V−Q245R、G020R−S101G−S103G−V104I−A232V−Q245R、G020R−S101G−S103S−V104I−A232V−Q245R、G020R−S101G−S103S−V104L−A232V−Q245R、G020R−S101G−V104I−T213A−A215F−A232V−Q245R、G020R−S101S−S103A−V104I−A232V−Q245R、G020R−S101S−S103A−V104V−A232V−Q245R、G020R−S101S−S103G−V104I−A232V−Q245R、G020R−S101S−S103G−V104V−A232V−Q245R、G020R−S101S−S103S−V104I−A232V−Q245R、G020R−S101S−S103S−V104L−A232V−Q245R、G020R−S101S−S103S−V104V−A232V−Q245R、G020R−S103N−S216F−Q236N−N252R、G020R−S144R−N185I−L233C−Q236N、G020R−S212F−H249R、G020R−S242R−N269R、G020R−T022R−E271L、G020R−T022R−N043R、G020R−T022R−N043R−S212F、G020R−T022R−N043R−W241R、G020R−T022R−S024R−S242R、G020R−T022R−S078R−S242R、G020R−T022R−S078R−W241R、G020R−T022R−S212F−W241R、G020R−T022R−S242R、G020R−T022R−W241R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116S−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T038A−N043R−S101A、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A232V、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T22W−S103A−V104I−A232V−Q245R、G023A−P052N−S144R−Y192W−S216F、G023A−P052N−Y192W−I198L−N252R、G023A−S024R−N117F−S212M−S216F、G023A−S078R−S216F−Q236N−H249R、G023A−Y091F−S101A−I198L−N252R、G023A−Y091F−V121F−Y192W−Q236N、G025R−E089I−N116A−P239S−A270C、G025R−G046R−V121F、G025R−N043A−E089I−N117F、G025R−S103N−R186K−A194F−T224A、G046R−A194F−S212M、G046R−E089I−Y091F−S101A−N116A、G046R−E089I−Y192W−L233C−A270C、G046R−N183D−N238L、G046R−Q059A−S103N−G211Q−S212M、G046R−Q059A−S106G−L217E−H249R、L148I−T213A−N252R、N018R−G020R−N043D、N018R−G020R−N043D−A230E−S242R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−R045T−A230E、N018R−G020R−N043R−N076D−H249R、N018R−G020R−N043R−N076D−S242R−H249R、N018R−G020R−N043R−R045T−S242R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−R045T、N018R−G020R−S024R−N043D−R045T−L233I−S242R、N018R−G020R−S024R−N043R−R045T−N076D−A230E、N018R−G020R−S024R−N076D−S087D−H249R、N018R−G020R−S024R−N076D−V150L−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R
−N269R、N018R−N043R−N076D−A230E、N018R−N043R−R045T−H249R、N018R−N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−R045T−S242R−H249R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−S242R−H249R、N018R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−V104I−A232V−Q245R、N018R−Q245R、N018R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−A230E、N018R−S024R−N043D−N076D−H249R、N018R−S024R−N043D−N076D−H249R−N269R、N018R−S024R−N043D−N076D−S078R−H249R、N018R−S024R−N043D−R045T−H249R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N043R−N076D−H249R、N018R−S024R−N043R−N076D−H249R−N269R、N018R−S024R−N043R−N076D−S087D−H249R、N018R−S024R−N043R−N076D−V150L−H249R、N018R−S024R−N076D−G211Q−A215F−H249R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−H249R、N018R−S024R−N076D−H249R−N269R、N018R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N018R−S024R−N076D−S078R−H249R、N018R−S024R−N076D−S078R−S087D−H249R、N018R−S024R−N076D−S078R−V150L−H249R、N018R−S024R−N076D−S087D−H249R−N269R、N018R−S024R−N076D−S087D−S242R−H249R、N018R−S024R−N076D−S087D−V150L−H249R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−S024R−N076D−S242R−H249R、N018R−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−V104I−H249R、N018R−S024R−N076D−V150L−H249R、N018R−S024R−R045T−S242R、N018R−S024R−S101G−V104I、N018R−S024R−S101G−V104I−A232V、N018R−S024R−S242R、N018R−S024R−V104I−H249R、N018R−S024R−V244R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−Q245R、N018R−S101G−S103A−H249R、N018R−S101G−S103A−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−S101G−V104I−A232V−H249R、N018R−S101G−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、N018R−S103A−A232V−H249R、N018R−S103A−V104I−H249R、N018R−T022R−S024R−N043D−N076D−H249R、N018R−T022R−S024R−N043R−N076D−H249R、N018R−T022R−S024R−N076D−H249R、N018R−T022R−S024R−N076D−S087D−H249R、N018R−T022R−S024R−N076D−V150L−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−T22K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−V104I−A232V−H249R、N043A−N062Q−A194F−G211Q、N043A−T057R−N117F−S144R−N183D、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−R045T−N076D−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S242R−H249R、N043R−N116A−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101A−N116A−A215F−N269R、N043R−S101A−N116A−N269R、N043R−S101A−N116A−T213A−A215F−N269R、N043R−S101A−N269R、N043R−S101A−T213A−N269R、N043R−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−A232V−Q245R−E271L、N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−A232V−S242R−Q245R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R、N043R−S242R−H249R、N043R−T213A−A215F−N269R、N062Q−S103N−N117F−A194F、N062Q−S103N−V121F−S144R−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S103A−V104I−Q109R、N076D−S103A−V104I−Q109R−Q245R、N076D−S103A−V104I−S212P−E271V、N076D−S103A−V104I−S212P−Q245L−E271V、N076D−S87R−S103A−V104I−S212P−E271V、N117F−A194F−T213A−A270C、N117F−T213A−A215F、P052N−S078R−S103N−L148I−T213A、P052N−S103N−N116A−L148I−Y192W、R019H−G020R−T022W−S078R−S101G−S103A−V104I−G211Q−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S009A−G020R−N043R−S212F、S009A−G020R−N043R−W241R、S009A−G020R−S024R−N043R、S009A−N043R−S078R、S009A−N043R−S078R−S242R、S009A−N043R−S212F、S009A−N043R−W241R、S009A−T022R−N043R−S078R、S009A−T022R−S078R−S212F、S009A−T022R−S078R−S212F−W241R、S009A−T022R−S212F−W241R、S024R−A215F−N269R、S024R−A232V−Q245R、S024R−G025R−N183D−Y192W−P239S、S024R−N043A−N117F−A194F−G211Q、S024R−N043D−H249R、S024R−N043D−
S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−A215F、S024R−N043R−A230E、S024R−N043R−A230E−S242R、S024R−N043R−H249R、S024R−N043R−N076D−H249R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N116A−A215F、S024R−N043R−N116A−A215F−N269R、S024R−N043R−N116A−N269R、S024R−N043R−N116A−T213A−N269R、S024R−N043R−R045T−N076D−A230E−H249R、S024R−N043R−R045T−N269R、S024R−N043R−R045T−S101A−N116A−A215F−N269R、S024R−N043R−R045T−S101A−N116A−T213A−N269R、S024R−N043R−R045T−S242R、S024R−N043R−R045T−T213A−A215F−N269R、S024R−N043R−S101A−A215F、S024R−N043R−S101A−A215F−N269R、S024R−N043R−S101A−N116A、S024R−N043R−S101A−N116A−A215F−N269R、S024R−N043R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−S242R、S024R−N062Q−V104L−S106G−H249R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−V104I−A232V−Q245R、S024R−N116A−T213A−N269R、S024R−R045T、S024R−R045T−N076D−A230E−S242R−H249R、S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S078R−S212F、S024R−S078R−V104L−N116A−N183D、S024R−S087D−S101G−S103A−V104I−A232V−Q245R、S024R−S101A−H120F−A194F−H249R、S024R−S101A−N269R、S024R−S101G−S103A−V104I−A232V−Q245R、S024R−S101G−S103A−V104I−V150L−A232V−Q245R、S024R−S101G−V104I−Q245R、S024R−S103A−Q245R、S024R−S103A−V104I−A232V−H249R、S024R−S103A−V104I−H249R、S024R−S103A−V104I−Q245R、S024R−Y167W−T224A−H249R、S078R−S087D−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−V150L−A232V−Q245R、S078R−S103N−S106G−Y167W−Q236N、S078R−V104L−T213A−A215F−T224A、S078R−Y091F−V121F−L233C−N252R、S087D−S101G−S103A−V104I−A232V−Q245R−N269R、S087R−S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S099F−S144R−Y167W−N252R、S101A−H120F−Y192W−A215F−T224A、S101A−S103A−V104I−T213A−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−Q245R、S101G−S103A−V104I−A232V−Q245R−E271L、S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−S242R−Q245R、S101G−S103A−V104I−A232V−V244R−Q245R、S101G−S103A−V104I−G115R−A232V−Q245R、S101G−S103A−V104I−N116A−T213A−A232V−Q245R−N269R、S101G−S103A−V104I−Q109R−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S101G−S103A−V104I−S212F−A232V−Q245R、S101G−S103A−V104I−V150L−A232V−Q245R−H249R、S101G−S103A−V104I−V150L−A232V−Q245R−N269R、S105T−S128N−S144R−L148I−S212M、S106G−N117F−N238L、S144R−G211Q−N238L−P239S−H249R、T022R−N043R−S101G−S103A−V104I−A232V−Q245R、T022R−N076D−S101G−S103A−V104I−A232V−Q245R、T022R−S087D−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−A232V−Q245R、T022W−S078R−Y167W−S212M−A270C、T057R−E089I−I198L、T057R−S099F−S105T−I198L−T213A、T057R−S099F−V121F−N185I−Y192W、T057R−Y167W−H249R、V004R−G020R−H249R、V004R−G020R−N043R、V004R−G020R−S024R、V004R−G020R−S024R−H249R、V004R−G020R−S024R−N043R、V004R−G020R−S024R−N043R−S242R、V004R−G020R−S024R−V244R、V004R−N043R−S101G−S103A−V104I−A232V−Q245R、V004R−S009A−G020R−N043R、V004R−S009A−G020R−N043R−S242R、V004R−S009A−G020R−S024R−S242R、V004R−S009A−G020R−S242R、V004R−S009A−N043R−W241R、V004R−S009A−S024R−N043R−W241R、V004R−S009A−S078R−W241R、V004R−S009A−W241R、V004R−S101G−S103A−V104I−A232V−Q245R、V104L−L217E−T224A−H249R−N252R、V104L−T213A−S216F、V121F−N252R−A270C、及び/又はY091F−S099F−S101A−S105T−Y167W; e)S101G−S103A−V104I−A232V−Q236H−Q245R−N252K、S101G−S103A−V104I−A232V−Q245R−N248R、S101G−S103A−V104I−G159R−A232V−Q245R−N248D、A232V−Q245R、E089I−N117F−N185I−A215F−L233C、G020R−E089I−L217E、G020R−G023A−V104L−Y192W−L233C、G020R−N043D−R045T−N076D−S242R−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−N043R−N076D−A230E−H249R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N116A−A215F−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−R045T−N116A−N269R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−A215F、G020R−S024R−K27R−N043D−S242R−H249R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S024R−N043R−N076D、G020R−S024R−N043R−R045T−A215F、G020R−S024R−N043R−R045T−N076D−S242R−H249R、G020R−S024R−N043R−R045T−N116A−T213A−A215F、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−T38I−N043R−R045T−N076D−S242R−H249R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q24
5R−E271G、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S101A−S103G−V104V−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、G020R−S103A−V104I−A232V−Q245R、G020R−S242R−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G025R−N043A−Y091F−I198L−A270C、G025R−S105T−S128N−S144R−A270C、G046R−E089I−S099F−R186K−S212M、G118R−A172V、G118R−A194T、G118R−Y209A−K235F、H017Y−S024R−T033S−P086W、I008T−S024R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、K235F−N243F、N018R−G020R−H249R、N018R−G020R−N043D−H249R、N018R−G020R−N043D−R045T−A230E−S242R、N018R−G020R−N043D−R045T−N076D−S242R、N018R−G020R−N043D−R045T−S240P、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043R、N018R−G020R−N043R−N076D、N018R−G020R−N043R−N076D−A230E−S242R、N018R−G020R−N043R−R045T−N076D−H249R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S242R、N018R−G020R−S024R−N043D−R045T−S242R、N018R−G020R−S024R−N043R−N076D−H249R、N018R−G020R−S024R−N043R−R045T−N076D−H249R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−L217E−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−R045T−N076D−S242R−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−N076D−A230E−S242R−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−N076D−S242R−H249R、N018R−N043R−R045T−N076D−A230E−S242R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−R045T−N076D−S242R、N018R−N043R−R045T−S242R、N018R−N076D−H249R、N018R−N076D−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N
076D−S101G−S103A−V104I−H249R、N018R−N076D−S101G−V104I−H249R、N018R−N076D−S103A−V104I−H249R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−A230E−H249R、N018R−S024R−N043D−A230E−S242R、N018R−S024R−N043D−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−N076D−S242R−H249R、N018R−S024R−N043D−N076D−V150L−H249R、N018R−S024R−N043D−S242R、N018R−S024R−N043D−S242R−H249R、N018R−S024R−N043R−N076D−L217E−H249R、N018R−S024R−N043R−N076D−S078R−H249R、N018R−S024R−N043R−R045T−A230E−H249R、N018R−S024R−N076D、N018R−S024R−N076D−A232V−H249R、N018R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−S024R−N076D−N116A−T213A−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−H249R、N018R−S024R−N076D−S101A−H249R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−S024R−N076D−S101G−A232V、N018R−S024R−N076D−S103A−A232V−Q245R、N018R−S024R−N076D−T213A−H249R、N018R−S024R−N076D−V104I、N018R−S024R−Q245R、N018R−S024R−R045T−A230E−S242R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−S242R、N018R−S024R−V104I、N018R−S024R−V30S−L31S−D32I−T33Q−G34V−I35F、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S101G−S103A−V104I、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S101G−V104I、N018R−S103A、N018R−S103A−V104I−A232V、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−T22W−S024R−N076D−T213A−A215F−H249R、N018R−V104I、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、N043D−S101G−S103A−V104I−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N04
3R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R、N062Q−S101A−Q236N−N252R−A270C、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N076D−S101G−S103A−V104I−A232V−S242R−Q245R、P005S−S024R−T033S−N243F、P014L−G020R−S024R−N043R−R045T−S101A−A215F、P052N−V104L−N183D−S216F−H249R、P086W−G118R、P086W−N243F、P086W−Y209A、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S242R−H249R、S024C−T033S、S024R−A232V、S024R−G046R−Y091F−V121F、S024R−G118R−K235F、S024R−N043A−S105T−S106G−I198L、S024R−N043D−R045T−S242R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R、S024R−N043D−S242R−H249R、S024R−N043R−N076D、S024R−N043R−N076D−A230E−S242R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−R045T−S242R−H249R、S024R−N043R−S101A−T213A、S024R−N076D−Q245R、S024R−N076D−S101G−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、S024R−N076D−S101G−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S103A−V104I−Q245R、S024R−N076D−V104I−Q245R、S024R−N243F、S024R−P086R−G118R、S024R−P086W−Y209A−K235F、S024R−P239Q、S024R−Q245R−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101G、S024R−S101G−Q245R、S024R−S101G−V104I−H249R、S024R−S103A−A232V、S024R−S103A−M175L−A232V−H249R、S024R−S141G、S024R−T033S、S024R−T033S−A194T、S024R−T033S−G118R−K235F、S024R−T033S−G118R−Y209A、S024R−T033S−K235F、S024R−T033S−S078R−G118R、S024R−T033S−S078R−N243F、S024R−T033S−Y209A、S024R−T033S−Y209A−N243F、S024R−T274I、S024R−V104I−H249R、S024R−V104I−Q245R、S024R−Y091F−I198L−A215F−P239S、S024R−Y209A、S024R−Y209A−K235F、S024R−Y209A−S242P、S078R−P086W、S078R−S099F−N116A−R186K−T224A、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−A232V、S101G−S103A−V104I−A232V−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S101G−S103A−V104I−Q245R、S105T−G211Q−S216F、S106G−N185I−S216F−Q236N、T022R−S101G−S103A−V104I−V150L−A232V−Q245R、T033S−G118D−A138V−Y209A、T033S−G118R−Y209A−、T033S−L148F、T033S−N243F、T033S−P086W、T033S−P201S、T033S−S078R、T033S−W241R、T033S−Y209A、T033S−Y209A−K235F、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、及び/又はV104L−H120F−R186K−S216F−N252R; f)A015T−T033S、A016T−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、A230E−H249R、A232V−H249R、E089I−S105T−N116A−A215F−S216F、E089I−Y091F−N185I−G211Q−A270C、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−N043R−N076D、G020R−N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−P052N−S101A−I198L−L233C、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S024R−N043D−N076D−H249R、G020R−S024R−N043D−N076D−S242R−H249R、G020R−S024R−N043D−R045T−A230E−S242R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S024R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−R045T−N076D−S242R−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022R−N269R、G020R−T022R−S078R−S212F−W241R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−N263S、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A21
5F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、G025R−N062Q−S128N−S144R−N185I、G025R−N116A−H120F−T224A−A270C、G118R−K235F、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−N043D−N076D−S242R−H249R、N018R−G020R−N043D−R045T−N076D−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−N043R−R045T−H249R、N018R−G020R−N043R−R045T−N076D−A230E−H249R、N018R−G020R−N076D、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N043R−N076D、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−
H249R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、N018R−N043D−A230E−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−N076D−S242R−H249R、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−N043R−N076D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−N043R−R045T−A230E−S242R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−A232V−H249R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N076D−S101G−I198T−A232V、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−N076D−S101G−V104I、N018R−N076D−S242R、N018R−N076D−S242R−H249R、N018R−N076D−V104I−Q245R−H249R、N018R−R045T−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N043D−N076D−S087D−H249R、N018R−S024R−N043D−N076D−S242R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−A232V、N018R−S024R−N076D−I198L−A215F−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−L217E−H249R−N269R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S087D−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、N018R−S024R−N076D−S101G、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、N018R−S024R−N076D−S103A−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−V150L−S242R−H249R、N018R−S024R−R045T−A230E−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A21
5F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T22W−S024R−N076D−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−V104I−A232V、N043A−Q059A−S101A−S216F−T224A、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S242R−H249R、N043R−A230E−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、N043R−R045T−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R−N269R、N076D−A232V−Q245R、N076D−Q245R、N076D−S101G−A232V−Q245R、N076D−S101G−S103A−Q245R、N076D−S101G−S103A−V104I−A232V−H249R、N076D−S101G−S103A−V104I−H249R、N076D−S101G−S103A−V104I−V150L−A232V−Q245R、N076D−S101G−V104I−H249R、N076D−S101G−V104I−Q245R、N076D−S103A−V104I−A232V−Q245R、N076D−S103A−V104I−Q245R、N076D−V104I−A232V−Q245R、N076D−V104I−Q245R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、P086W−K235F、P086W−Y209A−K235F、Q012H−V104A−G118R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、S024R−G118R−N243F−R269H、S024R−K235F−N243F、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−N076D−A230E−H249R、S024R−N076D−A232V−H249R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N076D−S101G、S024R−N076D−S101G−A232V−H249R、S024R−N076D−S101G−S103A−A232V、S024R−N076D−S101G−S103A−V104I−M175L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S101G−V104I−A232V−H249R、S024R−N076D−S103A−H249R、S024R−N076D−S103A−Q245R、S024R−N076D−S103A−V104I−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−R045T−S242R−A273V、S024R−R247H、S024R−S101G−S103A、S024R−S101G−S103A−A232V、S024R−S101G−S103A−V104I、S024R−S103A−Q245R−H249R、S024R−S103A−V104I、S024R−S106G−N116A−S212M−T224A、S024R−T033S−A151V、S024R−T03
3S−A174V−K235F、S024R−T033S−A228T、S024R−T033S−K235F−W241R、S024R−T033S−N243F、S024R−V104A、S024R−V104I−A232V、S024R−Y209A−N243F、S078R−K235F、S087D−S101G−S103A−V104I−A232V−S242R−Q245R、S099F−S105T−S106G−A194F−S212M、S101G−H249R、S101G−S103A−V104I、S101G−S103A−V104I−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R、S101G−S103A−V104I−G159D−A232V−Q245R−N248R、S101G−S103A−V104I−V150L−A232V−Q245R、S103A−A232V、S103A−A232V−H249R、S103A−A232V−Q245R、S103A−V104I−Q245R、S103N−H120F−Y167W−I198L−L233C、T022W−A194F−T213A−L233C−N238L、T022W−E089I−S216F、T033S−A048T、T033S−P086W−S156L−Y209A、T033S−P239T、T033S−T253A、T057R−N183D−Q236N、T143A−Y209A、V004E−T033S−S078R、V004R−S009A−T022R−S078R−S212F、及び/又はY209A−K235F;のうちの1つ以上を含み、任意選択で、次の変異:S103A、G159D、Q236H、Q245R、N248D及びN252Kのうちの1つ以上を含む、プロテアーゼ変異体を提供する。
−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R−E271G、S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、及びS024R−S101G−S103A−V104I−S128L−S130A−A158E−S188D−A232V−Q245R−N248D−H249R選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、このプロテアーゼ変異体のアミノ酸位置は、このプロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体を提供する。
、N183I、N183D、N183M、N183R、N183F、N183R、N185E、N185V、N185I、R186H、R186K、S188E、S188D、S188R、Y192H、Y192W、A194E、A194V、A194F、D197F、D197F、I198L、I198F、V203E、V203C、T208S、Y209S、Y209N、Y209F、Y209T、Y209E、Y209H、Y209G、Y209L、P210R、P210V、P210L、G211Q、G211R、S212I、S212M、S212F、T213A、Y214F、A215N、A215D、A215E、A215H、A215F、S216F、S216A、L217E、L217N、L217D、N218D、N218P、N218E、T224A、T224G、V227I、A230E、A231I、A231C、A232V、L233C、V234F、K235F、Q236F、Q236N、Q236H、N238R、N238K、N238L、P239K、P239G、P239R、P239R、P239H、P239T、P239N、P239S、P239F、S240R、W241R、S242L、S242R、N243F、N243R、V244R、Q245R、I246S、N248D、N248V、N248I、N248R、H249R、H249T、L250I、K251R、K251S、N252I、N252F、N252R、N252K、N252H、T253I、T253R、T253F、A254C、S256N、G258R、T260V、T260I、L262D、L262H、Y263F、S265F、L267V、L267N、L267M、N269I、N269R、A270C、E271I、E271H、E271V、E271H、E271M、E271L、E271P、E271A、E271F、E271T、A272F、A272F、A272R、A273F、A273I、及びT274Gからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、30、35、40、45、又は50箇所以下の変異により異なるアミノ酸配列からなり、プロテアーゼ変異体のアミノ酸位置は、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
H、Q245R、N248D/R、H249R、N252K/R、T253R、E271F、A1R、A230E、E271L、G115R、G20R、H249R、K235F、K27V/F/L、L75E、L82R、N18R、N269R、N43D、N43R、N76D、R45T、S212F、S242R、S24R、S78R、S9A、T22R、V121E、V244R、V28E、V30E、V4R、及びW241Rからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、30、35、40、45、又は50箇所以下の変異により異なるアミノ酸配列からなり、プロテアーゼ変異体のアミノ酸位置は、プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
4R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101D−S103N−N116L−S144R−A215D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N043R−S101G−S103A−V104I−G159D−S188D−L217E−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−S128I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−S101G−S103A−V104I−G159D−L217E−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022L−T038F−A048R−N062E−G100S−R186K、T033S−N043W−N218D−P239G−N243F、V026F−A048R−S105T−T213A−N218D−T224A、V026F−L031F−S078N−G102A−S160D、V026F−V051W−V104L−S106E、V104L−S105T−T213A−L217E−S256N、A016S−N062E−A158E−H249R、A016S−N062E−A158E−R186H−E271F、A016S−N062E−A158E−R186H−H249R、A016S−N062E−V104L−A158E−R186H−E271F、A016S−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、G020K−G023A−N062E−S188D、G020K−G023A−S024F−N062E−G118R−S188D−T213A、G020K−N043W−N062E−N116L−S188D−T213A−P239G、G020K−S024F−N062E−S188D−P239G、G023A−N062E−N116L−G118R、G023A−N062E−N116L−G118R−S188D−P239G、G023A−S024F−N062E−N116L−G118R、H017R−T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N062E−A158E−G159E−H249R、N062E−A158E−H249R、N062E−A158E−R186H−E271F、N062E−A158E−R186H−H249R、N062E−A158E−R186H−H249R−E271F、N062E−A158E−S188D−H249R、N062E−A158E−S188D−H249R−E271F、N062E−G159E−H249R、N062E−G159E−H249R−E271F、N062E−G159E−R186H−H249R、N062E−G159E−S188D−H249R、N062E−R186H−S188D−H249R−E271F、N062E−S101A−A158E−H249R、N062E−S101A−A158E−R186H−E271F、N062E−S101A−A158E−R186H−H249R−E271F、N062E−S101A−G159E−H249R、N062E−S101A−R186H−H249R、N062E−S101A−S188D−H249R、N062E−S101A−S188D−H249R−E271F、N062E−S101A−V104L−A158E−R186H−E271F、N062E−S128N−A158E−G159E−E271F、N062E−V104L−A158E−S188D−H249R−E271F、N076D−S101G−S103A−V104I−A232V−M222Q−Q245R、S024F−N062E−N116L−P239G、S024F−N062E−S188D−T213A、S024F−N116L、S024R−N043R−N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F−E271F、S101A−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S128N−A158E−R186H−E271F、S101A−S128N−A158E−Y209E−H249R、S101A−V104L−A158E−R186H−S188D−H249R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222Q−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A232V−M222Q−Q245R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、S128N−A158E−G159E−E271F、S128N−A158E−H249R、S128N−A158E−R186H−E271F、S128N−A158E−R186H−H249R、S128N−A158E−R186H−S188D−E271F、S128N−A158E−S188D−E271F、S128N−A158E−S188D−H249R、S128N−A158E−S188D−Y209E−E271F、S128N−A158E−Y209E−、T022A−N043R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N062E−A158E、T022A−S024R−S101D−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A
−S024R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S024R−S103A−V104I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S128N−A158E−H249R、V104L−S128N−A158E−H249R、V104L−S128N−A158E−R186H−E271F、V104L−S128N−A158E−R186H−H249R、及びV104L−S128N−A158E−S188D−H249Rから選択されるアミノ酸置換の組みを含むアミノ酸配列からなり、このプロテアーゼ変異体の合計正味電荷は、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
48D−H249R、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、S078N−V104L−G118R−S128D、S101A−A158E−R186H−H249R、S101A−A158E−R186H−S188D−H249R、S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、S101A−S103G−A158E−R186H−H249R、S101A−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−G159E−A232V−Q245R−N248D−H249R、S101A−S128N−A158E−H249R、S101A−S128N−A158E−S188D−Y209E−E271F、S101A−S128N−A158E−Y209E、S101A−S128N−P129E−R186H−H249R、S101A−V104L−A158E−R186H−H249R、S101A−V104L−A158E−R186H−S188D−E271F、S101A−V104L−S128N−A158E−R186H−E271F、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−A232V−M222S−Q245R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−S130A−A158E−N183D−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101S−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N043R−N062E−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−N043R−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S024R−N043R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S024R−S101D−S103A−V104I−G118R−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S101A−A158E−R186H−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D、T022A−S103A−V104I−G159D−S188D−A232V−N248D、T022L−L031F−G102A−S128D−T224A−N243F、T022L−T038F−V121F−S160D−A272F、V026F−S078N−G159C−R186K−N243F、V104L−A158E−H249R、V104L−A158E−R186H−H249R、V104L−A158E−R186H−H249R−E271F、V104L−A158E−R186H−S188D−H249R、V104L−A158E−R186H−S188D−H249R−E271F、V104L−A158E−S188D−H249R−E271F、V104L−S128N−A158E−R186H−S188D−E271F、V104L−S128N−G159E−E271F、V104L−S128N−R186H−S188D−H249R、及びV121F−N185E−T224A−P239Gから選択されるアミノ酸置換の組みを含むアミノ酸配列からなり、このプロテアーゼ変異体の合計正味電荷は、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、ププロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
かつA016S−S128N−R186H−E271F、N076D−S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R−E271G、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−G102A−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、A016S−A158E−H249R、A016S−A158E−H249R−E271F、A016S−A158E−R186H−H249R、A016S−L111V−S188D−、A016S−T022A−A158E−R186H−E271F、A048R−S078N−N116L−N185E−L217E−P239G、A048R−S128D−N185E−P239G、A158E−R186H−H249R−E271F、E089P−S101A−P129E−R186H、G020K−G023A−N043W−N116L−S188D−T213A−P239G、G020K−G023A−N062E−N116L−G118R−T213A、G020K−G023A−S024F−N062E−S188D−T213A−P239G、G020K−K027R−P129E−S166D−P239G、G020K−S024F−N062E−P239G、G020K−S024F−T033S−P129E−A194E、G023A−G100S−A194E−S212M、G023A−N043W−N116L−G118R−S188D、G023A−S024F−G118R−S188D−P239G、G023A−S024F−K027R−N062E、G023A−S024F−N043W−N062E−N116L−G118R、G023A−S024F−N116L−G118R−S188D−T213A、G023A−S024F−N116L−S188D−P239G、K027R−G100S−G118R−S160D−S188D−N243F、K027R−S101D−S103N−S105T−A272F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、N062E−S078N−N116L−T224A、N062E−V104L−A158E−R186H−S188D−H249R、N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S024F−G102A−R186K−T213A−L217E−N243F、S024F−N043W−G118R−S188D、S024F−N043W−V104L−V121F−P129E、S024F−N116L−G118R−S188D−P239G、S024F−S103N−V104L−G118R−S188D、S024R−N043R−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−N076D−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101A−L111V−P129E、S101A−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−V104L−S128N−A158E−R186H、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S128N−P129E−R186H、T022A−A158E−R186H−H249R−E271F、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S103A−V104I−S128I−G159D−S188D−A232V−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S128N−A158E−R186H、T022A−S128N−R186H−S188D−、T022A−V104L−A158E−H249R、T022A−V104L−R186H−S188D−H249R、T022L−G023A−K027R−S101D−V104L−S216F、T022L−S078N−N116L−P129E−S256N、T022L−S078N−S128D−T213A、T033S−G118R−P129E−A194E−P239G、T033S−S105T−S188D−S216F、V026F−V104L−S256N−A272F、T022A−N043R−S103A−V104I−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S101D−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249R、V104L−L148I−S188D−H249R、S024R−S101A−S103A−V104I−A158E−S166D−S188D−L217E−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、T022A−N043R−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271F、S101A−S103G−V104V−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104V−G159E−A232V−Q245R−N248D−H249R、G023A−S024F−V051W−A158E、K027R−T038F−G102A−N116L、N062E−S078N−S144R−S212M、L031F−N116L−S256N−A272F、T022L−T033S−V104L−N116L−S160D−R186K、S024F−G118R−P129E−R186K−T213A、N043W−S105T−T213A−A215D−S216F、L031F−S105T−R186K−S188D、V026F−A194E−T213A−S256N、S103N−S160D−L250I−S256N、S024R−S101G−S103A−V104I−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N062E−S103A−V104I−G118R−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−L217D−A232V、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D、T022A−S024R−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R
−N248D−E271F、G020K−N043W−S188D−T213A、S024F−N062E−G118R−P239G、G023A−N043W−S188D−T213A、G020K−S024F−N043W−N062E−N116L−G118R−S188D−P239G、G020K−N116L−S188D−P239G、G020K−N043W−N062E−G118R、G020K−N043W−N116L−S188D−T213A、G020K−S024F、G023A−N043W−N116L−P239G、G023A−S024F−N043W−N116L−G118R−S188D−P239G、G020K−G023A−N043W−T213A、及びG023A−S024F−N062E−G118R−T213A−P239Gから選択されるアミノ酸置換の組みを含むアミノ酸配列からなり、このプロテアーゼ変異体の合計正味電荷は、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、ププロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
32V−Q245R、G020R−S101S−S103S−V104I−A232V−Q245R、G020R−S101S−S103S−V104L−A232V−Q245R、G020R−S101S−S103S−V104V−A232V−Q245R、G020R−S103N−S216F−Q236N−N252R、G020R−S144R−N185I−L233C−Q236N、G020R−S212F−H249R、G020R−S242R−N269R、G020R−T022R−E271L、G020R−T022R−N043R、G020R−T022R−N043R−S212F、G020R−T022R−N043R−W241R、G020R−T022R−S024R−S242R、G020R−T022R−S078R−S242R、G020R−T022R−S078R−W241R、G020R−T022R−S212F−W241R、G020R−T022R−S242R、G020R−T022R−W241R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116S−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T038A−N043R−S101A、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A232V、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T22W−S103A−V104I−A232V−Q245R、G023A−P052N−S144R−Y192W−S216F、G023A−P052N−Y192W−I198L−N252R、G023A−S024R−N117F−S212M−S216F、G023A−S078R−S216F−Q236N−H249R、G023A−Y091F−S101A−I198L−N252R、G023A−Y091F−V121F−Y192W−Q236N、G025R−E089I−N116A−P239S−A270C、G025R−G046R−V121F、G025R−N043A−E089I−N117F、G025R−S103N−R186K−A194F−T224A、G046R−A194F−S212M、G046R−E089I−Y091F−S101A−N116A、G046R−E089I−Y192W−L233C−A270C、G046R−N183D−N238L、G046R−Q059A−S103N−G211Q−S212M、G046R−Q059A−S106G−L217E−H249R、L148I−T213A−N252R、N018R−G020R−N043D、N018R−G020R−N043D−A230E−S242R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−R045T−A230E、N018R−G020R−N043R−N076D−H249R、N018R−G020R−N043R−N076D−S242R−H249R、N018R−G020R−N043R−R045T−S242R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−R045T、N018R−G020R−S024R−N043D−R045T−L233I−S242R、N018R−G020R−S024R−N043R−R045T−N076D−A230E、N018R−G020R−S024R−N076D−S087D−H249R、N018R−G020R−S024R−N076D−V150L−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−N076D−A230E、N018R−N043R−R045T−H249R、N018R−N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−R045T−S242R−H249R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−S242R−H249R、N018R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−V104I−A232V−Q245R、N018R−Q245R、N018R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−A230E、N018R−S024R−N043D−N076D−H249R、N018R−S024R−N043D−N076D−H249R−N269R、N018R−S024R−N043D−N076D−S078R−H249R、N018R−S024R−N043D−R045T−H249R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N043R−N076D−H249R、N018R−S024R−N043R−N076D−H249R−N269R、N018R−S024R−N043R−N076D−S087D−H249R、N018R−S024R−N043R−N076D−V150L−H249R、N018R−S024R−N076D−G211Q−A215F−H249R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−H249R、N018R−S024R−N076D−H249R−N269R、N018R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N018R−S024R−N076D−S078R−H249R、N018R−S024R−N076D−S078R−S087D−H249R、N018R−S024R−N076D−S078R−V150L−H249R、N018R−S024R−N076D−S087D−H249R−N269R、N018R−S024R−N076D−S087D−S242R−H249R、N018R−S024R−N076D−S087D−V150L−H249R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−S024R−N076D−S242R−H249R、N018R−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−V104I−H249R、N018R−S024R−N076D−V150L−H249R、N018R−S024R−R045T−S242R、N018R−S024R−S101G−V104I、N018R−S024R−S101G−V104I−A232V、N018R−S024R−S242R、N018R−S024R−V104I−H249R、N018R−S024R−V244R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S1
01G−Q245R、N018R−S101G−S103A−H249R、N018R−S101G−S103A−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−S101G−V104I−A232V−H249R、N018R−S101G−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、N018R−S103A−A232V−H249R、N018R−S103A−V104I−H249R、N018R−T022R−S024R−N043D−N076D−H249R、N018R−T022R−S024R−N043R−N076D−H249R、N018R−T022R−S024R−N076D−H249R、N018R−T022R−S024R−N076D−S087D−H249R、N018R−T022R−S024R−N076D−V150L−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−T22K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−V104I−A232V−H249R、N043A−N062Q−A194F−G211Q、N043A−T057R−N117F−S144R−N183D、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−R045T−N076D−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S242R−H249R、N043R−N116A−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101A−N116A−A215F−N269R、N043R−S101A−N116A−N269R、N043R−S101A−N116A−T213A−A215F−N269R、N043R−S101A−N269R、N043R−S101A−T213A−N269R、N043R−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−A232V−Q245R−E271L、N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−A232V−S242R−Q245R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R、N043R−S242R−H249R、N043R−T213A−A215F−N269R、N062Q−S103N−N117F−A194F、N062Q−S103N−V121F−S144R−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S103A−V104I−Q109R、N076D−S103A−V104I−Q109R−Q245R、N076D−S103A−V104I−S212P−E271V、N076D−S103A−V104I−S212P−Q245L−E271V、N076D−S87R−S103A−V104I−S212P−E271V、N117F−A194F−T213A−A270C、N117F−T213A−A215F、P052N−S078R−S103N−L148I−T213A、P052N−S103N−N116A−L148I−Y192W、R019H−G020R−T022W−S078R−S101G−S103A−V104I−G211Q−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S009A−G020R−N043R−S212F、S009A−G020R−N043R−W241R、S009A−G020R−S024R−N043R、S009A−N043R−S078R、S009A−N043R−S078R−S242R、S009A−N043R−S212F、S009A−N043R−W241R、S009A−T022R−N043R−S078R、S009A−T022R−S078R−S212F、S009A−T022R−S078R−S212F−W241R、S009A−T022R−S212F−W241R、S024R−A215F−N269R、S024R−A232V−Q245R、S024R−G025R−N183D−Y192W−P239S、S024R−N043A−N117F−A194F−G211Q、S024R−N043D−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−A215F、S024R−N043R−A230E、S024R−N043R−A230E−S242R、S024R−N043R−H249R、S024R−N043R−N076D−H249R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N116A−A215F、S024R−N043R−N116A−A215F−N269R、S024R−N043R−N116A−N269R、S024R−N043R−N116A−T213A−N269R、S024R−N043R−R045T−N076D−A230E−H249R、S024R−N043R−R045T−N269R、S024R−N043R−R045T−S101A−N116A−A215F−N269R、S024R−N043R−R045T−S101A−N116A−T213A−N269R、S024R−N043R−R045T−S242R、S024R−N043R−R045T−T213A−A215F−N269R、S024R−N043R−S101A−A215F、S024R−N043R−S101A−A215F−N269R、S024R−N043R−S101A−N116A、S024R−N043R−S101A−N116A−A215F−N269R、S024R−N043R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−S242R、S024R−N062Q−V104L−S106G−H249R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−V104I−A232V−Q245R、S024R−N116A−T213A−N269R、S024R−R045T、S024R−R045T−N076D−A230E−S242R−H249R、S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S078R−S212F、S024R−S078R−V104L−N116A−N183D、S024R−S087D−S101G−S103A−V104I−A232V−Q245R、S024R−S101A−H120F−A194F−H249R、S024R−S101A−N269R、S024R−S101G−S103A−V104I−A232V−Q245R、S024R−S101G−S103A−V104I−V150L−A232V−Q245R、S024R−S101G−V104I−Q245R、S024R−S103A−Q245R、S024R−S103A−V104I−A232V−H249R、S024R−S103A−V104I−H249R、S024R−S103A−V104I−Q245R、S024R−Y167W−T224A−H249R、S078R−S087D−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−V150L−A232V−Q245R、S078R−S103N−S106G−Y167W−Q236N、S078R−V104L−T213A−A215F−T224A、S078R−Y091F−V121F−L233C−N252R、S087D−S101G−S103A−V104I−A232V−Q245R−N269R、S087R−S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S099F−S144R−Y167W−N252R、S101A−H120F−Y192W−A215F−T224A、S101A−S103A−V104I−T213A−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−Q245R、S101G−S103A−V104I−A232V−Q245R−E271L、S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−S242R−Q245R、S101G−S103A−V104I−A232V−V244R−Q245R、S101G−S103A−V10
4I−G115R−A232V−Q245R、S101G−S103A−V104I−N116A−T213A−A232V−Q245R−N269R、S101G−S103A−V104I−Q109R−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S101G−S103A−V104I−S212F−A232V−Q245R、S101G−S103A−V104I−V150L−A232V−Q245R−H249R、S101G−S103A−V104I−V150L−A232V−Q245R−N269R、S105T−S128N−S144R−L148I−S212M、S106G−N117F−N238L、S144R−G211Q−N238L−P239S−H249R、T022R−N043R−S101G−S103A−V104I−A232V−Q245R、T022R−N076D−S101G−S103A−V104I−A232V−Q245R、T022R−S087D−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−A232V−Q245R、T022W−S078R−Y167W−S212M−A270C、T057R−E089I−I198L、T057R−S099F−S105T−I198L−T213A、T057R−S099F−V121F−N185I−Y192W、T057R−Y167W−H249R、V004R−G020R−H249R、V004R−G020R−N043R、V004R−G020R−S024R、V004R−G020R−S024R−H249R、V004R−G020R−S024R−N043R、V004R−G020R−S024R−N043R−S242R、V004R−G020R−S024R−V244R、V004R−N043R−S101G−S103A−V104I−A232V−Q245R、V004R−S009A−G020R−N043R、V004R−S009A−G020R−N043R−S242R、V004R−S009A−G020R−S024R−S242R、V004R−S009A−G020R−S242R、V004R−S009A−N043R−W241R、V004R−S009A−S024R−N043R−W241R、V004R−S009A−S078R−W241R、V004R−S009A−W241R、V004R−S101G−S103A−V104I−A232V−Q245R、V104L−L217E−T224A−H249R−N252R、V104L−T213A−S216F、V121F−N252R−A270C、及びY091F−S099F−S101A−S105T−Y167Wから選択されるアミノ酸置換の組みを含むアミノ酸配列からなり、このプロテアーゼ変異体の合計正味電荷は、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、ププロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G025R−N043A−Y091F−I198L−A270C、G025R−S105T−S128N−S144R−A270C、G046R−E089I−S099F−R186K−S212M、G118R−A172V、G118R−A194T、G118R−Y209A−K235F、H017Y−S024R−T033S−P086W、I008T−S024R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、K235F−N243F、N018R−G020R−H249R、N018R−G020R−N043D−H249R、N018R−G020R−N043D−R045T−A230E−S242R、N018R−G020R−N043D−R045T−N076D−S242R、N018R−G020R−N043D−R045T−S240P、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043R、N018R−G020R−N043R−N076D、N018R−G020R−N043R−N076D−A230E−S242R、N018R−G020R−N043R−R045T−N076D−H249R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S242R、N018R−G020R−S024R−N043D−R045T−S242R、N018R−G020R−S024R−N043R−N076D−H249R、N018R−G020R−S024R−N043R−R045T−N076D−H249R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−L217E−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−R045T−N076D−S242R−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−N076D−A230E−S242R−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−N076D−S242R−H249R、N018R−N043R−R045T−N076D−A230E−S242R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−R045T−N076D−S242R、N018R−N043R−R045T−S242R、N018R−N076D−H249R、N018R−N076D−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−N076D−S101G−V104I−H249R、N018R−N076D−S103A−V104I−H249R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−A230E−H249R、N018R−S024R−N043D−A230E−S242R、N018R−S024R−N043D−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−N076D−S242R−H249R、N018R−S024R−N043D−N076D−V150L−H249R、N018R−S024R−N043D−S242R、N018R−S024R−N043D−S242R−H249R、N018R−S024R−N043R−N076D−L217E−H249R、N018R−S024R−N043R−N076D−S078R−H249R、N018R−S024R−N043R−R045T−A230E−H249R、N018R−S024R−N076D、N018R−S024R−N076D−A232V−H249R、N018R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−S024R−N076D−N116A−T213A−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−H249R、N018R−S024R−N076D−S101A−H249R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−S024R−N076D
−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−S024R−N076D−S101G−A232V、N018R−S024R−N076D−S103A−A232V−Q245R、N018R−S024R−N076D−T213A−H249R、N018R−S024R−N076D−V104I、N018R−S024R−Q245R、N018R−S024R−R045T−A230E−S242R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−S242R、N018R−S024R−V104I、N018R−S024R−V30S−L31S−D32I−T33Q−G34V−I35F、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S101G−S103A−V104I、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S101G−V104I、N018R−S103A、N018R−S103A−V104I−A232V、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−T22W−S024R−N076D−T213A−A215F−H249R、N018R−V104I、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、N043D−S101G−S103A−V104I−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R、N062Q−S101A−Q236N−N252R−A270C、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N076D−S101G−S103A−V104I−A232V−S242R−Q245R、P005S−S024R−T033S−N243F、P014L−G020R−S024R−N043R−R045T−S101A−A215F、P052N−V104L−N183D−S216F−H249R、P086W−G118R、P086W−N243F、P086W−Y209A、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S242R−H249R、S024C−T033S、S024R−A232V、S024R−G046R−Y091F−V121F、S024R−G118R−K235F、S024R−N043A−S105T−S106G−I198L、S024R−N043D−R045T−S242R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R、S024R−N043D−S242R−H249R、S024R−N043R−N076D、S024R−N043R−N076D−A230E−S242R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−R045T−S242R−H249R、S024R−N043R−S101A−T213A、S024R−N076D−Q245R、S024R−N076D−S101G−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、S024R−N076D−S101G−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S103A−V104I−Q245R、S024R−N076D−V104I−Q245R、S024R−N243F、S024R−P086R−G118R、S024R−P086W−Y209A−K235F、S024R−P239Q、S024R−Q245R−H
249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101G、S024R−S101G−Q245R、S024R−S101G−V104I−H249R、S024R−S103A−A232V、S024R−S103A−M175L−A232V−H249R、S024R−S141G、S024R−T033S、S024R−T033S−A194T、S024R−T033S−G118R−K235F、S024R−T033S−G118R−Y209A、S024R−T033S−K235F、S024R−T033S−S078R−G118R、S024R−T033S−S078R−N243F、S024R−T033S−Y209A、S024R−T033S−Y209A−N243F、S024R−T274I、S024R−V104I−H249R、S024R−V104I−Q245R、S024R−Y091F−I198L−A215F−P239S、S024R−Y209A、S024R−Y209A−K235F、S024R−Y209A−S242P、S078R−P086W、S078R−S099F−N116A−R186K−T224A、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−A232V、S101G−S103A−V104I−A232V−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S101G−S103A−V104I−Q245R、S105T−G211Q−S216F、S106G−N185I−S216F−Q236N、T022R−S101G−S103A−V104I−V150L−A232V−Q245R、T033S−G118D−A138V−Y209A、T033S−G118R−Y209A−、T033S−L148F、T033S−N243F、T033S−P086W、T033S−P201S、T033S−S078R、T033S−W241R、T033S−Y209A、T033S−Y209A−K235F、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、及びV104L−H120F−R186K−S216F−N252Rから選択されるアミノ酸置換の組みを含むアミノ酸配列からなり、このプロテアーゼ変異体の合計正味電荷は、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、ププロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
20R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N043R−N076D、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、N018R−N043D−A230E−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−N076D−S242R−H249R、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−N043R−N076D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−N043R−R045T−A230E−S242R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−A232V−H249R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N076D−S101G−I198T−A232V、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−N076D−S101G−V104I、N018R−N076D−S242R、N018R−N076D−S242R−H249R、N018R−N076D−V104I−Q245R−H249R、N018R−R045T−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N043D−N076D−S087D−H249R、N018R−S024R−N043D−N076D−S242R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D
−A215F−H249R、N018R−S024R−N076D−A232V、N018R−S024R−N076D−I198L−A215F−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−L217E−H249R−N269R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S087D−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、N018R−S024R−N076D−S101G、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、N018R−S024R−N076D−S103A−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−V150L−S242R−H249R、N018R−S024R−R045T−A230E−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N0
18R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T22W−S024R−N076D−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−V104I−A232V、N043A−Q059A−S101A−S216F−T224A、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S242R−H249R、N043R−A230E−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、N043R−R045T−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R−N269R、N076D−A232V−Q245R、N076D−Q245R、N076D−S101G−A232V−Q245R、N076D−S101G−S103A−Q245R、N076D−S101G−S103A−V104I−A232V−H249R、N076D−S101G−S103A−V104I−H249R、N076D−S101G−S103A−V104I−V150L−A232V−Q245R、N076D−S101G−V104I−H249R、N076D−S101G−V104I−Q245R、N076D−S103A−V104I−A232V−Q245R、N076D−S103A−V104I−Q245R、N076D−V104I−A232V−Q245R、N076D−V104I−Q245R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、P086W−K235F、P086W−Y209A−K235F、Q012H−V104A−G118R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、S024R−G118R−N243F−R269H、S024R−K235F−N243F、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−N076D−A230E−H249R、S024R−N076D−A232V−H249R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N076D−S101G、S024R−N076D−S101G−A232V−H249R、S024R−N076D−S101G−S103A−A232V、S024R−N076D−S101G−S103A−V104I−M175L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S101G−V104I−A232V−H249R、S024R−N076D−S103A−H249R、S024R−N076D−S103A−Q245R、S024R−N076D−S103A−V104I−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−R045T−S242R−A273V、S024R−R247H、S024R−S101G−S103A、S024R−S101G−S103A−A232V、S024R−S101G−S103A−V104I、S024R−S103A−Q245R−H249R、S024R−S103A−V104I、S024R−S106G−N116A−S212M−T224A、S024R−T033S−A151V、S024R−T033S−A174V−K235F、S024R−T033S−A228T、S024R−T033S−K235F−W241R、S024R−T033S−N243F、S024R−V104A、S024R−V104I−A232V、S024R−Y209A−N243F、S078R−K235F、S087D−S101G−S103A−V104I−A232V−S242R−Q245R、S099F−S105T−S106G−A194F−S212M、S101G−H249R、S101G−S103A−V104I、S101G−S103A−V104I−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R、S101G−S103A−V104I−G159D−A232V−Q245R−N248R、S101G−S103A−V104I−V150L−A232V−Q245R、S103A−A232V、S103A−A232V−H249R、S103A−A232V−Q245R、S103A−V104I−Q245R、S103N−H120F−Y167W−I198L−L233C、T022W−A194F−T213A−L233C−N238L、T022W−E089I−S216F、T033S−A048T、T033S−P086W−S156L−Y209A、T033S−P239T、T033S−T253A、T057R−N183D−Q236N、T143A−Y209A、V004E−T033S−S078R、V004R−S009A−T022R−S078R−S212F、Y209A−K235F、N043R−N076D−H249R、N018R−R045T、G020R−N076D−A230E−S242R、G020R−S024R−N043D−R045T、S024R−N043D−N076D−S242R−H249R、G020R−R045T−H249R、N043R−N076D−S153A−H249R、N043R−N076D−A230E−H249R、N018R−N043D−N076D−H249R、G020R−N043R−N076D−V227I、L111I−A215F−P239S、S024R−N116A−R186K−L233C−Q236N、G023A−S103N−S106G−S212M−A215F、Y209A−N243F、S024R−T033S−P129H−N184D−T253M、S024R−A085V−P086W−G118R−K235F、S024R−A272P、S024R−R269C、G0
20R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R
−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−L217E−S242R−H249R、N076D−S087D−S101G−S103A−V104I−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−Q245R、及びS101G−S103A−V104I−V150L−A232V−S242R−Q245Rから選択されるアミノ酸置換の組みを含むアミノ酸配列からなり、このプロテアーゼ変異体の合計正味電荷は、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、ププロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
えば、サブチリシン変異体)は、配列番号2のアミノ酸配列とは50個以下、40個以下、30個以下、35個以下、25個以下、20個以下、19個以下、18個以下、17個以下、16個以下、15個以下、14個以下、13個以下、12個以下、11個以下、10個以下、9個以下、8個以下、7個以下、6個以下、5個以下、4個以下、3個以下、2個以下、又は1個以下のアミノ酸残基により異なるアミノ酸配列からなり、サブチリシン変異体のアミノ酸位置は、ププロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
129E−X209E、X062E−X209E、X022A−X209E、X103G−X209E、X158E−X209E、X188D−X209E、X104L−X209E、X089P−X209E、及びX186H−X209Eから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
12F−X241R、X020R−X043R−X212F−X241R、X009A−X043R−X241R、X020R−X043R−X271L、X020R−X022R−X078R−X241R、X020R−X024R−X043R−X242R、X020R−X022R−X043R−X241R、X009A−X020R−X043R−X212F、X004R−X009A−X020R−X024R−X242R、X020R−X043R−X249R−X271L、X020R−X022R−X024R−X242R、X009A−X022R−X078R−X212F、X020R−X043R−X242R−X271L、X009A−X022R−X078R−X212F−X241R、X004R−X020R−X024R−X249R、X020R−X022R−X271L、X020R−X022R−X043R−X212F、X004R−X020R−X024R−X043R−X242R、X004R−X020R−X024R−X043R、X004R−X009A−X022R−X078R−X212F、X020R−X022R−X078R−X212F−X241R、及びX020R−X022R−X269Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
、X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X232V−X245R−X248D、X016S−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X158E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X159E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X188D−X2
32V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024K−X101G−X103A−X104I−X128N−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X148I−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X148I−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、及びX101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
X128N−X129E−X186H、X158E−X186H−X249R−X271F、X016S−X158E−X249R、X016S−X158E−X186H−X249R、X016S−X022A−X158E−X186H−X271F、X089P−X101A−X129E−X186H、X022A−X128N−X158E−X186H、X101A−X104L−X128N−X158E−X186H、X022A−X128N−X186H−X188D−、X062E−X104L−X158E−X186H−X188D−X249R、X022A−X158E−X186H−X249R−X271F、X022A−X104L−X158E−X249R、X101A−X111V−X129E、X016S−X158E−X249R−X271F、X016S−X111V−X188D−、X022A−X104L−X186H−X188D−X249R、及びX104L−X148I−X188D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
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X183D−X211Q−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X213A−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X116A−X198L−X249R、X018R−X024R−X076D−X183D−X211Q−X213A−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X213A−X249R、X018R−X024R−X076D−X116A−X183D−X198L−X215F−X249R、X018R−X022W−X024R−X076D−X183D−X198L−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X183D−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X215F−X249R、X018R−X020R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X020R−X022W−X101A−X103A−X104I−X183D−X198L−X215F−X232V−X245R、X076D−X101G−X103A−X104I−X249R、X018R−X020R−X024R−X076D−X183D−X198L−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X215F−X249R、X018R−X020R−X024R−X076D−X211Q−X213A−X249R、X018R−X024R−X076D−X116A−X183D−X211Q−X213A−X249R、X018R−X024R−X076D−X116A−X183D−X198L−X249R、X018R−X020R−X024R−X076D−X211Q−X243D−X249R、X018R−X020R−X045T−X076D−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X022W−X024R−X076D−X183D−X198L−X211Q−X213A−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X022W−X024R−X076D−X116A−X198L−X211Q−X213A−X215F−X249R、X024R−X076D−X101G、X018R−X020R−X024R−X076D−X101A−X198L−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X183D−X215F−X249R、X018R−X043D−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X211Q−X213A−X245R、X020R−X024R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X020R−X045T−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X024R−X076D−X101A−X183D−X198L−X211Q−X249R、X018R−X022W−X024R−X076D−X183D−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X116A−X198L−X211Q−X215F−X249R−X269S、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X215F−X249R、X020R−X022W−X101A−X103A−X104I−X183D−X213A−X215F−X232V−X245R、X018R−X024R−X076D−X086V−X101A−X183D−X198L−X211Q−X249R、X018R−X076D−X101G−X198T−X232V、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X211Q−X213A−X215F−X249R、X018R−X024R−X076D−X183D−X249R−X248T、X018R−X076D−X104I−X245R−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X211Q−X213A−X215F−X249R、X018R−X020R−X024R−X076D−X101A−X249R、X018R−X020R−X024R−X076D−X101A−X116A−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X198L−X211Q−X213A−X249R、X043R−X045T−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X043R−X045T−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X076D−X101G−X104I、X020R−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X249R、X043D−X076D−X101G−X103A−X104I−X232V−X245R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X249R、X018R−X076D−X104I、X018R−X020R−X043D−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X020R−X022W−X024R−X076D−X183D−X211Q−X249R、X018R−X024R−X076D−X101A−X183D−X198L−X211Q−X215F−X249R、X101G−X104I、X018R−X022W−X024R−X076D−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X211Q−X213A−X215F−X249R、X018R−X020R−X024R−X076D−X116A−X183D−X215F−X249R−X263D、X018R−X022W−X024R−X076D−X101A−X183D−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X198L−X215F−X249R−X269H、X018R−X043D−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X078R−X101G−X103A−X104I−X217E−X232V−X245R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X198L−X213A−X215F−X249R、X018R−X020R−X024R−X076D−X183D−X198L−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X211Q−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X198L−X211Q−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X249R、X020R−X022W−X101G−X103A−X104I−X116A−X183D−X198L−X211Q−X213A−X215F−X232V−X245R、X104I−X232V、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X183D−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X211Q−X213A−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X249R、X043D−X045T−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X211Q−X249R、X018R−X020R−X043R−X101G−X103A−X104I−X217E−X232V−X245R、X024R−X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X043R−X045T−X076D−X078R−X101G−X103A−X104I−X166F−X176P−X179V−X184T−X187P−X194P、X018R−X022W−X024R−X041E−X076D−X101A−X160T−X183D−X211Q−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X213A−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X198L−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X183D−X211Q−X215F−X249R、X024R−X076D−X104I、X018R−X076D−X1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5F−X249R、X018R−X024R−X031F−X076D−X116A−X183D−X211Q−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X213A−X249R−X269S、X018R−X020R−X024R−X076D−X101A−X116A−X198L−X215F−X249R、X018R−X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X114T−X198L−X211Q−X215F−X249R、X024R−X043R−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X024R−X076D−X103A−X104I−X232V、X018R−X020R−X022W−X024R−X076D−X101A−X198L−X211Q−X215F−X249R、X101G−X104I−X232V、X018R−X022W−X024R−X076D−X183D−X198L−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X183D−X213A−X249R、X018R−X024R−X076D−X101A−X183D−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X211Q−X213A−X249R、X018R−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X211Q−X215F−X249R−X260A、X076D−X249R、X018R−X022W−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X116A−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X249R、X076D−X104I−X249R、X020R−X022W−X101A−X103A−X104I−X116A−X183D−X211Q−X213A−X215F−X232V−X245R、X024R−X043R−X045T−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X018R−X020R−X022W−X024R−X076D−X183D−X198L−X215F−X249R、X018R−X076D−X101G−X103A、X020R−X024R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R、X101G−X103A−X232V、X024R−X076D−X101G−X232V、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X183D−X198L−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X116A−X156V−X183D−X211Q−X215F−X249R−X269S、X045T−X076D−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X249R、X018R−X020R−X022W−X024R−X076D−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X249R、X018R−X076D−X101G、X018R−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X249R、X018R−X076D−X232V、X018R−X020R−X024R−X076D−X101A−X232V−X245R、X018R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X018R−X022W−X024R−X076D−X183D−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X211Q−X213A−X237D−X249R、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R−X275S、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X024R−X076D、X018R−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X076D−X104I−X232V−X249R、X018R−X076D−X103A−X232V、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X175E−X183D−X211Q−X215F−X249R、X018R−X020R−X043D−X078R−X101G−X103A−X104I−X217E−X232V−X245R−X273E、X020R−X024R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X005S−X101G−X103A−X104I−X232V−X245R−X249R、X103A−X104I−X232V、X018R−X020R−X024R−X068A−X076D−X101A−X116A−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X198L−X215F−X249R−X275S、X018R−X024R−X076D−X183D−X198L−X211Q−X213A−X249R、及びX043D−X045T−X101G−X103A−X104I−X232V−X245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
018R−X020R−X024R−X043R−X076D−X249R、X020R−X101A−X103G−X104V−X232V−X245R、X043D−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X076D−X217E−X249R−X269R、及びX018R−X024R−X076D−X217E−X242R−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
応させて番号付けされる、核酸を提供する。
04I−X118R−X159D−X188D−X217D−X232V−X248D、X022A−X062E−X103A−X104I−X118R−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X101D−X103A−X104I−X118R−X129E−X159D−X188D−X217D−X232V、X022A−X024R−X103A−X104I−X159D−X188D−X217D−X232V−X248D、X022A−X024R−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X217D−X232V−X248D−X271F、及びX022A−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X245R−X248D−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
5F、X118R−X172V、X017Y−X024R−X033S−X086W、X033S−X148F、X024R−X118R−X235F、X033S−X078R、X033S−X243F、X024C−X033S、X118R−X194T、X033S−X209A、X118R−X209A−X235F、X024R−X033S−X209A−X243F、X024R−X033S−X235F、X024R−X033S−X118R−X235F、X024R−X141G、X024R−X274I、X024R−X033S−X209A、X086W−X235F、X024R−X209A−X243F、X004E−X033S−X078R、X086W−X209A−X235F、X015T−X033S、X033S−X086W−X156L−X209A、X024R−X118R−X243F−X269H、X209A−X235F、X024R−X247H、X024R−X033S−X228T、X078R−X235F、X024R−X033S−X174V−X235F、X024R−X235F−X243F、X024R−X033S−X235F−X241R、X024R−X033S−X151V、X024R−X104A、X033S−X048T、X012H−X104A−X118R、X118R−X235F、X033S−X253A、X143A−X209A、X024R−X033S−X243F、X033S−X239T、X209A−X243F、X024R−X033S−X129H−X184D−X253M、X024R−X085V−X086W−X118R−X235F、X024R−X272P、及びX024R−X269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
R、X024R−X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R−X271G、X101G−X103A−X104I−X129Q−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X130A−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129Q−X158E−X188D−X217E−X232V−X245R−X248D−X249R、及びX024R−X101G−X103A−X104I−X128L−X130A−X158E−X188D−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
148I−H249R、G159E−H249R、S101A−H249R、S188D−H249R、V104L−H249R、Y209E−H249R、T022A−H249R、S128N−H249R、S103G−H249R、E089P−H249R、T022A−L111V、S101A−L111V、A016S−L111V、V104L−L111V、N062E−L111V、S103G−L111V、E089P−L111V、A016S−L148I、N062E−L148I、T022A−L148I、P129E−L148I、V104L−L148I、S103G−L148I、S128N−L148I、S101A−L148I、E089P−L148I、L111V−L148I、A016S−N062E、T022A−N062E、N062E−P129E、T022A−P129E、S128N−P129E、A016S−P129E、S101A−P129E、V104L−P129E、E089P−P129E、S103G−P129E、L111V−P129E、N062E−R186H、S128N−R186H、S101A−R186H、T022A−R186H、A016S−R186H、A158E−R186H、E089P−R186H、P129E−R186H、G159E−R186H、S103G−R186H、V104L−R186H、L111V−R186H、L148I−R186H、N062E−S101A、T022A−S101A、A016S−S101A、E089P−S101A、N062E−S103G、T022A−S103G、A016S−S103G、S101A−S103G、E089P−S103G、N062E−S128N、A016S−S128N、T022A−S128N、S101A−S128N、V104L−S128N、E089P−S128N、S103G−S128N、L111V−S128N、L111V−S188D、N062E−S188D、A016S−S188D、L148I−S188D、T022A−S188D、S128N−S188D、S101A−S188D、V104L−S188D、E089P−S188D、P129E−S188D、G159E−S188D、R186H−S188D、S103G−S188D、A158E−S188D、A016S−T022A、A016S−V104L、T022A−V104L、S101A−V104L、N062E−V104L、S103G−V104L、E089P−V104L、G159E−Y209E、L111V−Y209E、S101A−Y209E、A016S−Y209E、S128N−Y209E、L148I−Y209E、P129E−Y209E、N062E−Y209E、T022A−Y209E、S103G−Y209E、A158E−Y209E、S188D−Y209E、V104L−Y209E、E089P−Y209E、及びR186H−Y209Eから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
024R−V104A、T033S−A048T、G118R−K235F、T033S−T253A、T143A−Y209A、T033S−P239T、Y209A−N243F、S024R−A272P、及びS024R−R269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、及びS101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
R186H−S188D−E271F、V104L−A158E−R186H−H249R、S101A−S128N−A158E−S188D−Y209E−E271F、N062E−S101A−R186H−S188D−E271F、A016S−N062E−A158E−H249R−E271F、N062E−S128N−A158E、N062E−S128N−G159E−H249R、N062E−S101A−A158E−S188D−H249R、S101A−S128N−A158E−H249R、N062E−A158E−R186H−S188D−H249R、A016S−V104L−A158E−R186H−E271F、N062E−L148I−G159E、N062E−S101A−A158E−R186H−H249R、N062E−S101A−R186H−S188D−H249R、V104L−A158E−R186H−S188D−H249R、N062E−S101A−V104L−R186H−S188D−E271F、T022A−S101A−A158E−R186H−H249R、S101A−S128N−A158E−Y209E、A158E−R186H−S188D−H249R−E271F、V104L−A158E−R186H−S188D−H249R−E271F、S101A−V104L−A158E−R186H−H249R、V104L−A158E−H249R、S101A−V104L−S128N−A158E−R186H−E271F、A016S−V104L−S188D−H249R、S101A−V104L−A158E−R186H−S188D−E271F、V104L−S128N−G159E−E271F、V104L−A158E−R186H−H249R−E271F、A158E−R186H−H249R、S101A−A158E−R186H−H249R、V104L−A158E−S188D−H249R−E271F、A016S−S128N−A158E−R186H、V104L−S128N−R186H−S188D−H249R、A016S−S101A−S128N−R186H、A016S−N062E−S128N−R186H−E271F、A016S−S128N−R186H−E271F、S128N−P129E−R186H、A158E−R186H−H249R−E271F、A016S−A158E−H249R、A016S−A158E−R186H−H249R、A016S−T022A−A158E−R186H−E271F、E089P−S101A−P129E−R186H、T022A−S128N−A158E−R186H、S101A−V104L−S128N−A158E−R186H、T022A−S128N−R186H−S188D−、N062E−V104L−A158E−R186H−S188D−H249R、T022A−A158E−R186H−H249R−E271F、T022A−V104L−A158E−H249R、S101A−L111V−P129E、A016S−A158E−H249R−E271F、A016S−L111V−S188D−、T022A−V104L−R186H−S188D−H249R、及びV104L−L148I−S188D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、N018R−S024R−N076D−T213A−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、G020R−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S101G−S103A−V104I、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−S103A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−G211Q−H249R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−S024R−N076D−A232V−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−Q245R、S024R−V104I−Q245R、S101G−A232V、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、S024R−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、S024R−S101G−V104I−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−V104I、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−T213A−H249R、S024R−V104I−H249R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−N076D−S103A−V104I−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q245R−E271G、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、S024R−S103A−M175L−A232V−H249R、N018R−S024R−N076D−N116A−T213A−H249R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−A232V、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、S024R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、S101G−S103A−V104I−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R
−S103A−A232V、N018R−S024R−N076D−S101A−G211Q−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101G−A232V、A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、S024R−N076D−S103A−V104I−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S103A−V104I−A232V、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、S024R−N076D−V104I−Q245R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−N076D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、N018R−S024R−N076D−N116A−H249R、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−S101G−Q245R、S024R−N076D−S101G−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、S024R−S101G、N018R−T22W−S024R−N076D−T213A−A215F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−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088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S024R−N076D−Q245R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N018R−S103A、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−V104I、S101G−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S103A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、S101G−H249R、S024R−N076D−S101G−S103A−V104I−M175L−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S103A−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−A232V、S024R−S103A−V104I、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−S103A−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、S103A−V104I−Q245R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、A016T−N043R−R045T−N076D−S101G−S10
3A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101G、N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−A215F−H249R、N018R−V104I−A232V、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S101G−A232V−H249R、S103A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S024R−N076D−S103A−V104I−H249R、S024R−S101G−S103A−V104I、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N018R−N076D−A232V−H249R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、A232V−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N076D−V104I−Q245R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、S024R−S101G−S103A−A232V、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、S103A−A232V−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、S024R−S103A−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、S103A−A232V、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−A232V、N018R−T022W−S024R−N076D−S101A−N116A−H249R、G020R−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−N263S、S024R−N076D−S101G−V104I−A232V−H249R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、S024R−S101G−S103A、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−V104I−A232V、N018R−S024R−N076D−N183D−G211Q−H249R、G020R−N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N183D−
T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、S024R−N076D−A232V−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、G020R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N076D−S101G−S103A−Q245R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T22W−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N076D−Q245R、N076D−S101G−V104I−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、G020R−S024R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S101G−S103A−V104I、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N076D−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−Q245R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183
D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N076D−V104I−A232V−Q245R、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N076D−S101G−S103A−V104I−A232V−H249R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、N076D−S101G−S103A−V104I−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、S024R−N076D−S101G、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−N076D−S101G−I198T−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−N076D−V104I−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−V104I、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G
211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、及びN043D−R045T−S101G−S103A−V104I−A232V−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
078R−H249R、G020R−S101G−S103G−V104I−A232V−Q245R、G020R−S101G−S103A−V104L−A232V−Q245R、G020R−S101G−S103A−V104V−A232V−Q245R、G020R−S101G−S103S−V104I−A232V−Q245R、G020R−S101G−S103S−V104L−A232V−Q245R、G020R−S101S−S103S−V104I−A232V−Q245R、G020R−S101S−S103S−V104L−A232V−Q245R、G020R−S101A−S103A−V104L−A232V−Q245R、G020R−S101S−S103S−V104V−A232V−Q245R、G020R−S101S−S103A−V104I−A232V−Q245R、G020R−S101S−S103A−V104V−A232V−Q245R、G020R−S101S−S103G−V104I−A232V−Q245R、G020R−S101S−S103G−V104V−A232V−Q245R、G020R−S101A−S103A−V104V−A232V−Q245R、G020R−S101A−S103S−V104I−A232V−Q245R、G020R−S101A−S103S−V104V−A232V−Q245R、N018R−S024R−N043R−N076D−S078R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−S242R−Q245R、N018R−G020R−S024R−N076D−L217E−H249R、N018R−S024R−N043R−N076D−L217E−H249R、N018R−S024R−N043D−N076D−S242R−H249R、N018R−G020R−S024R−N043R−N076D−H249R、G020R−S101A−S103G−V104V−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−L217E−H249R−N269R、及びN018R−S024R−N076D−L217E−S242R−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、及びN076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D、T022A−S024R−S101D−S103A−V104I−G118R−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−S103A−V104I−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S101D−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S024R−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−N062E−S103A−V104I−G118R−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−L217D−A232V、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D、T022A−S024R−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−L217D−A232V−N248D−E271F、及びT022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
43F、L021M−S024R−T033S、S024R−T033S−P086W、T033S−K235F、S078R−P086W−Y209A、S024R−T033S−Y209A−K235F、T033S−P086W−G118R、S024R−T033S−S078R−Y209A、T033S−P086W−G118R−Y209A−N243F、P086W−Y209A−N243F、P005S−S078R−G118R−W241R、S024R−A174T、T033S−Y209A−N243F、P086W−G118R−A133V、S024R−T033S−G118R、S024R−P086W−Y209A−K235F、P086W−Y209A、I008T−S024R、P086W−G118R、T033S−W241R、P005S−S024R−T033S−N243F、S024R−Y209A−S242P、S024R−T033S−S078R−G118R、S024R−T033S−A194T、S024R−N243F、S024R−Y209A、S024R−T033S−G118R−Y209A、T033S−P086W、S024R−T033S、S024R−T033S−S078R−N243F、P086W−N243F、T033S−G118D−A138V−Y209A、T033S−Y209A−K235F、S024R−P086R−G118R、T033S−P201S、S024R−P239Q、T033S−G118R−Y209A−、S078R−P086W、K235F−N243F、S024R−Y209A−K235F、G118R−A172V、H017Y−S024R−T033S−P086W、T033S−L148F、S024R−G118R−K235F、T033S−S078R、T033S−N243F、S024C−T033S、G118R−A194T、T033S−Y209A、G118R−Y209A−K235F、S024R−T033S−Y209A−N243F、S024R−T033S−K235F、S024R−T033S−G118R−K235F、S024R−S141G、S024R−T274I、S024R−T033S−Y209A、P086W−K235F、S024R−Y209A−N243F、V004E−T033S−S078R、P086W−Y209A−K235F、A015T−T033S、T033S−P086W−S156L−Y209A、S024R−G118R−N243F−R269H、Y209A−K235F、S024R−R247H、S024R−T033S−A228T、S078R−K235F、S024R−T033S−A174V−K235F、S024R−K235F−N243F、S024R−T033S−K235F−W241R、S024R−T033S−A151V、S024R−V104A、T033S−A048T、Q012H−V104A−G118R、G118R−K235F、T033S−T253A、T143A−Y209A、S024R−T033S−N243F、T033S−P239T、Y209A−N243F、S024R−T033S−P129H−N184D−T253M、S024R−A085V−P086W−G118R−K235F、S024R−A272P、及びS024R−R269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
R−N248D−H249R、S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−N183D−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R−E271G、S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、及びS024R−S101G−S103A−V104I−S128L−S130A−A158E−S188D−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、核酸を提供する。
のサブチリシンGG36プロテアーゼが配列番号2で示されるアミノ酸配列からなり、このプロテアーゼ変異体は、配列番号2のアミノ酸配列とは、G20K、G20R、G23A、S24F、S24R、N43R、N43W、R45T、N62E、N76D、S101A、N116A、N116L、G118R、S128I、P129E、S188D、T213A、A215F、L217E、P239G、及びN269Rからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、このプロテアーゼ変異体のアミノ酸位置は、このプロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体を提供する。
106G、S106T、S106E、S106D、S106A、S106V、S106F、I107M、I107F、A108I、A108G、Q109M、L111V、L111I、E112V、E112L、E112Q、A114G、G115K、G115R、N116K、N116A、N116L、N117F、G118R、G118I、M119C、H120A、H120F、H120R、V121F、V121F、V121E、N123G、N123E、L124S、S128D、S128F、S128L、S128N、S128H、S128M、S128I、S128Q、P129E、S132A、S132E、A138G、S144R、V147L、L148I、A158E、G159D、G159E、G159C、S160D、S166D、S166E、Y167W、M175V、V177C、D181A、Q182R、N183I、N183D、N183M、N183R、N183F、N183R、N185E、N185V、N185I、R186H、R186K、S188E、S188D、S188R、Y192H、Y192W、A194E、A194V、A194F、D197F、D197F、I198L、I198F、V203E、V203C、T208S、Y209S、Y209N、Y209F、Y209T、Y209E、Y209H、Y209G、Y209L、P210R、P210V、P210L、G211Q、G211R、S212I、S212M、S212F、T213A、Y214F、A215N、A215D、A215E、A215H、A215F、S216F、S216A、L217E、L217N、L217D、N218D、N218P、N218E、T224A、T224G、V227I、A230E、A231I、A231C、A232V、L233C、V234F、K235F、Q236F、Q236N、Q236H、N238R、N238K、N238L、P239K、P239G、P239R、P239R、P239H、P239T、P239N、P239S、P239F、S240R、W241R、S242L、S242R、N243F、N243R、V244R、Q245R、I246S、N248D、N248V、N248I、N248R、H249R、H249T、L250I、K251R、K251S、N252I、N252F、N252R、N252K、N252H、T253I、T253R、T253F、A254C、S256N、G258R、T260V、T260I、L262D、L262H、Y263F、S265F、L267V、L267N、L267M、N269I、N269R、A270C、E271I、E271H、E271V、E271H、E271M、E271L、E271P、E271A、E271F、E271T、A272F、A272F、A272R、A273F、A273I、及びT274Gからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、30、35、40、45、又は50箇所以下の変異により異なるアミノ酸配列からなり、プロテアーゼ変異体のアミノ酸位置は、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、核酸を提供する。
の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体を提供する。
−A158E、A016S−G159E、N062E−R186H、S128N−G159E、N062E−S188D、N062E−S128N、L148I−G159E、S103G−A158E、L111V−G159E、A158E−E271F、A016S−S188D、T022A−L111V、S128N−A158E、A016S−A158E、V104L−A158E、S128N−R186H、G159E−Y209E、N062E−S101A、L111V−Y209E、L148I−S188D、S101A−Y209E、T022A−S188D、A016S−T022A、S128N−P129E、A016S−Y209E、A016S−S128N、T022A−E089P、S128N−Y209E、E089P−A158E、N062E−S103G、R186H−E271F、A016S−P129E、E089P−G159E、L111V−H249R、S101A−P129E、L148I−Y209E、T022A−G159E、P129E−H249R、P129E−Y209E、V104L−P129E、S128N−S188D、L111V−A158E、T022A−A158E、N062E−Y209E、N062E−H249R、S101A−R186H、E089P−P129E、P129E−E271、T22A−L111V−G159E、S101A−S103G−V104L−Y209E、S101A−S103G−V104L−G159E、S101A−S103G−V104L−S188D、S101G−S103A−V104I−G159D、T22A−S103G−G159E、T22A−S128N−E271F−Y209E、T22A−Y209E−E271F、T22A−S101A−Y209E、S101A−Y209E−E271F、T22A−L111V−S128N、T22A−S101A−G159E、S101A−S103G−V104L、T22A−S101A−S103G−V104L、S101A−S103G−V104L、S101G−S103A−V104I、S101A−S103G−V104L−S128N、S103A−V104I−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−V104I−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N248D、N62E−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、N62E−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R、T22A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−S24R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−T253R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T22A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N238R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N76D、及び/又はS101G−S103A−V104I−G159E−A232V−Q245R−N248D−E271F。
R−N043R−S242R−E271L、S009A−T022R−S078R−S212F−W241R、V004R−G020R−S024R−H249R、G020R−T022R−E271L、G020R−T022R−N043R−S212F、V004R−G020R−S024R−N043R−S242R、V004R−G020R−S024R−N043R、V004R−S009A−T022R−S078R−S212F、G020R−T022R−S078R−S212F−W241R、及びG020R−T022R−N269Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−L148I−A158E−A232V−Q245R−N248D、A016S−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V
104I−L148I−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、及びS101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
16S−A158E−H249R−E271F、A016S−L111V−S188D−、T022A−V104L−R186H−S188D−H249R、及びV104L−L148I−S188D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
01G−S103A−V104I−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−N116A−G211Q−H249R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S101G−S103A−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−S101G−V104I−A232V−H249R、G020R−T22W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−H249R、S024R−S101G−S103A−V104I−A232V−Q245R、G020R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−V104I−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A215F−A232V−Q245R、S024R−S103A−V104I−H249R、N018R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101G−V104I−Q245R、G020R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、S024R−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−Q245R、S024R−S103A−Q245R、S024R−S103A−V104I−Q245R、G020R−S078R−S101G−A232V−Q245R、N018R−S024R−N076D−V104I−H249R、N018R−S024R−V104I−H249R、S024R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−A215F−H249R、R019H−G020R−T022W−S078R−S101G−S103A−V104I−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S103A−V104I−A232V−Q245R、N018R−S103A−V104I−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−S024R−S101G−V104I−A232V、S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−S024R−S101G−V104I、G020R−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−Q245R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−N076D−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、A001T−N018R−S024R−N076D−N116A−T213A−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、N018R−S024R−N076D−T213A−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、G020R−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−T21
3A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S101G−S103A−V104I、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−S103A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−G211Q−H249R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−S024R−N076D−A232V−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−Q245R、S024R−V104I−Q245R、S101G−A232V、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、S024R−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、S024R−S101G−V104I−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−V104I、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−T213A−H249R、S024R−V104I−H249R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−N076D−S103A−V104I−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q245R−E271G、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、S024R−S103A−M175L−A232V−H249R、N018R−S024R−N076D−N116A−T213A−H249R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−A232V、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、S024R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、S101G−S103A−V104I−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S103A−A232V、N018R−S024R−N076D−S101A−G211Q−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101G−A232V、A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、S024R−N076D−S103A−V104I−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S103A−V104I−A232V、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−A232V−Q245
R−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、S024R−N076D−V104I−Q245R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−N076D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、N018R−S024R−N076D−N116A−H249R、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−S101G−Q245R、S024R−N076D−S101G−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、S024R−S101G、N018R−T22W−S024R−N076D−T213A−A215F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−V104I、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S024R−N076D−Q245R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N018R−S103A、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q
245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−V104I、S101G−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S103A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、S101G−H249R、S024R−N076D−S101G−S103A−V104I−M175L−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S103A−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−A232V、S024R−S103A−V104I、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−S103A−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、S103A−V104I−Q245R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、A016T−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101G、N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−A215F−H249R、N018R−V104I−A232V、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S101G−A232V−H249R、S103A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S024R−N076D−S103A−V104I−H249R、S024R−S101G−S103A−V104I、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−
A215F−H249R、N018R−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N018R−N076D−A232V−H249R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、A232V−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N076D−V104I−Q245R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、S024R−S101G−S103A−A232V、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、S103A−A232V−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、S024R−S103A−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、S103A−A232V、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−A232V、N018R−T022W−S024R−N076D−S101A−N116A−H249R、G020R−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−N263S、S024R−N076D−S101G−V104I−A232V−H249R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、S024R−S101G−S103A、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−V104I−A232V、N018R−S024R−N076D−N183D−G211Q−H249R、G020R−N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N183D−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、S024R−N076D−A232V−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、G020R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N076D−S101G−S103A−Q245R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T22W−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024
R−N076D−S101A−I198L−G211Q−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N076D−Q245R、N076D−S101G−V104I−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、G020R−S024R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S101G−S103A−V104I、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N076D−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−Q245R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N076D−V104I−A232V−Q245R、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N076D−S101G−S103A−V104I−A232V−H249R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A
215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、N076D−S101G−S103A−V104I−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、S024R−N076D−S101G、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−N076D−S101G−I198T−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−N076D−V104I−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−V104I、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232
V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、及びN043D−R045T−S101G−S103A−V104I−A232V−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
020R−S101A−S103A−V104I−G118R−A232V−Q245R、G020R−S024R−N116A−T213A、N043R−S101A−N116A−A215F−N269R、S024R−N043R−S101A−N116A、S024R−N043R−S101A−N116A−A215F−N269R、G020R−S101G−S103A−V104I−A215F−A232V−Q245R、N043R−S101A−N269R、S024R−N043R−N116A−T213A−N269R、G020R−S024R−N043R−R045T−S101A−T213A、S024R−N043R−N116A−A215F−N269R、G020R−S024R−T213A−A215F、G020R−N116A−N269R、S024R−N116A−T213A−N269R、N043R−S101A−N116A−N269R、S101G−S103A−V104I−N116A−T213A−A232V−Q245R−N269R、S024R−N043R−R045T−S101A−N116A−A215F−N269R、G020R−N043R−S101A−N269R、S101A−S103A−V104I−T213A−A232V−Q245R−N269R、S024R−A215F−N269R、N043R−S101A−N116A−T213A−A215F−N269R、N043R−S101A−T213A−N269R、G020R−S024R−N043R−R045T−N116A−T213A、S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−R045T−S101A−N116A−T213A−N269R、S024R−N043R−R045T−N269R、G020R−N043R−R045T−S101A−N269R、S024R−N043R−N116A−N269R、G020R−S024R−N043R−R045T、N043R−N116A−N269R、S024R−N043R−S101A−A215F−N269R、S024R−N043R−R045T−T213A−A215F−N269R、G020R−S024R−R045T−N269R、G020R−N043R−S101A−N116A−T213A−A215F、G020R−S101G−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N116A−N269R、G020R−S101A−N116A−N269R、S024R−N043R−A215F、G020R−S024R−T213A、S024R−N043R−S101A−A215F、G020R−S024R−N043R−R045T−N116A、G020R−S024R−N043R−R045T−S101A−N269R、G020R−S024R−S101A−A215F、G020R−S024R−N116A−T213A−A215F、G020R−S024R−N116A、G020R−S024R−S101A−N116A、N043R−T213A−A215F−N269R、S024R−S101A−N269R、S024R−N043R−N116A−A215F、G020R−T038A−N043R−S101A、G020R−S024R−N116A−A215F、S024R−N043R−S101A−T213A、P014L−G020R−S024R−N043R−R045T−S101A−A215F、G020R−S024R−A215F、G020R−N116A−A215F−N269R、G020R−R045T−N116A−N269R、G020R−S024R−N043R−R045T−A215F、及びG020R−S024R−N043R−R045T−N116A−T213A−A215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
R−N248D−H249R−E271F、T022A−S101G−G102A−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、及びT022A−N043R−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
ミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
R−T033S−K235F−W241R、S024R−T033S−A151V、S024R−V104A、T033S−A048T、Q012H−V104A−G118R、G118R−K235F、T033S−T253A、T143A−Y209A、S024R−T033S−N243F、T033S−P239T、Y209A−N243F、S024R−T033S−P129H−N184D−T253M、S024R−A085V−P086W−G118R−K235F、S024R−A272P、及びS024R−R269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、このサブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体を提供する。
せて番号付けされる、サブチリシン変異体を提供する。
、Y209N、Y209S、L217E、A231I、P239R、P239S、W241R、S242R、S242L、N243R、V244R、N248I、H249R、N252R、T253R、E271T、E271V、E271L、E271H、E271F、E271P、A1R、S9A、S212F及びN269R、のうちの2つ以上から選択され;並びに/又は次の変異の組:T022R−S024R、S009A−E271L、N018R−W241R、N018R−G115R、N043R−H249R、G020R−H249R、V004R−H249R、G020R−S024R、N018R−H249R、S009A−G020R、G020R−W241R、S009A−S078R、G020R−G115R、N018R−S024R、S024R−S242R、T022R−G115R、N018R−N043R、G020R−N043R、N018R−S242R、S242R−N269R、N018R−V244R、S024R−N269R、G020R−E271L、S024R−E271L、V004R−S009A、G020R−N269R、A001R−S024R、V244R−E271L、S009A−N018R、W241R−E271L、V004R−S024R、S009A−H249R、S009A−T022R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−S24R、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N252K、S101G−S103A−V104L−A232V−Q236H−Q245R−N248D−N252K、のうちの1つ以上から選択される。
ポリヌクレオチドを含む単離された、実質的に純粋の、又は組み換えDNAコンストラクト、本発明の少なくとも1種のポリヌクレオチドを含む単離された又は組み換え細胞、本発明の少なくとも1種のポリヌクレオチドを含む細胞を含む細胞培養物、本発明の少なくとも1種の核酸又はポリヌクレオチドを含む細胞培養物、並びにこのようなベクター、核酸、発現ベクター、発現カセット、DNAコンストラクト、細胞、細胞培養物、又はこれらの任意の組み合わせ又はこれらの混合物などを1種以上含む組成物を提供する。
に導入され、一部の実施形態では、好ましくは大腸菌細胞又は形質転換受容性のバチルス細胞に導入される。プラスミドDNAコンストラクト又はベクターを利用して、核酸(例えば、DNA)をバチルス細胞又は大腸菌細胞に導入する方法、及びこのようなプラスミドDNAコンストラクト又はベクターにより細胞を形質転換する方法は周知である。一部の実施形態では、プラスミドは、続いて大腸菌細胞から単離され、バチルス細胞に導入される。しかしながら、必ずしも大腸菌などの微生物を介在させることは本質的ではなく、一部の実施形態では、DNAコンストラクト又はベクターは直接バチルス宿主に導入される。
10S、X14K、X16S、X17R、X18R、X20R、X22A、X22R、X24R、X24W、X25R、X25V、X26F、X42I、X43R、X43A、X46R、X52F、X52E、X52N、X57R、X59A、X62E、X62Q、X68A、X68C、X71G、X72C、X74C、X75A、X75F、X75R、X76D、X78R、X82R、X86W、X89P、X89T、X89G、X89H、X89I、X89V、X89W、X91N、X94N、X100S、X101A、X101N、X101G、X101D、X103G、X103N、X104L、X104I、X106V、X106G、X108I、X111V、X112V、X115K、X115R、X117F、X118I、X121F、X128D、X128F、X128L、X128N、X129E、X144R、X148I、X158E、X159E、X160D、X166D、X185E、X185I、X186H、X188E、X188D、X197F、X203E、X209S、X209N、X209F、X209T、X209E、X209H、X209G、X210R、X212I、X212F、X214F、X215N、X215D、X215E、X217E、X217N、X224A、X230E、X231I、X236F、X238R、X238K、X239K、X239G、X239R、X239S、X241R、X242R、X242L、X243R、X244R、X248I、X248V、X249R、X250I、X252R、X253R、X262D、X263F、X265F、X267V、X267N、X269I、X269R、X271F、X271I、X271H、X271P、X271T、X271V、X271L及びX272F、のうちの1つ以上、好ましくは、2つ以上を含む、少なくとも1種のプロテアーゼ変異体を含む。
236H−X245R−X248D−X252K、X101G−X103A−X104L−X159D−X232V−X245R−X248D−X252K、X101G−X103A−X104L−X159D−X232V−X236H−X248D−X252K、X101G−X103A−X104L−X159D−X232V−X236H−X245R−X252K、X101G−X103A−X104L−X159D−X232V−X236H−X245R−X248D、X62E−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X62E−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X249R、X22A−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X24R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X253R、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X22A−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X238R、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X159D−X232V−X245R−X248D、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X76D及びX101G−X103A−X104I−X159E−X232V−X245R−X248D−X271Fのうちの1つ以上を含む、少なくとも1種にプロテアーゼ変異体を含む。
X241R、X242R、X242L、X243R、X244R、X248I、X249R、X252R、X253R、X271T、X271V、X271L、X271H、X271F、X271P、X1R、X9A、X212F及びX269Rのうちの2つ以上を含み、並びに/あるいは次の変異の組:X022R−X024R、X009A−X271L、X018R−X241R、X018R−X115R、X043R−X249R、X020R−X249R、X004R−X249R、X020R−X024R、X018R−X249R、X009A−X020R、X020R−X241R、X009A−X078R、X020R−X115R、X018R−X024R、X024R−X242R、X022R−X115R、X018R−X043R、X020R−X043R、X018R−X242R、X242R−X269R、X018R−X244R、X024R−X269R、X020R−X271L、X024R−X271L、X004R−X009A、X020R−X269R、X001R−X024R、X244R−X271L、X009A−X018R、X241R−X271L、X004R−X024R、X009A−X249R、X009A−X022R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X24R、X101G−X103A−X104L−X159D−X232V−X236H−X245R−X252K、X101G−X103A−X104L−X232V−X236H−X245R−X248D−X252Kのうちの少なくも1つを含む、少なくとも1種のプロテアーゼ変異体を含み、ここで、この少なくとも1種のプロテアーゼ変異体は、配列番号2のアミノ酸配列を有するB.レンタスのサブチリシンGG36プロテアーゼと比較して、合計正味電荷が0、+1、+2、+3、+4又は+5である。
D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N238R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N76D及びS101G−S103A−V104I−G159E−A232V−Q245R−N248D−E271F、のうちの1つ以上を含む、少なくとも1種のプロテアーゼ変異体を含む。
、A016S−L148I、A158E−H249R、A016S−N062E、L111V−S188D、T022A−N062E、N062E−L148I、T022A−P129E、N062E−E271F、N062E−A158E、A016S−G159E、N062E−R186H、S128N−G159E、N062E−S188D、N062E−S128N、L148I−G159E、S103G−A158E、L111V−G159E、A158E−E271F、A016S−S188D、T022A−L111V、S128N−A158E、A016S−A158E、V104L−A158E、S128N−R186H、G159E−Y209E、N062E−S101A、L111V−Y209E、L148I−S188D、S101A−Y209E、T022A−S188D、A016S−T022A、S128N−P129E、A016S−Y209E、A016S−S128N、T022A−E089P、S128N−Y209E、E089P−A158E、N062E−S103G、R186H−E271F、A016S−P129E、E089P−G159E、L111V−H249R、S101A−P129E、L148I−Y209E、T022A−G159E、P129E−H249R、P129E−Y209E、V104L−P129E、S128N−S188D、L111V−A158E、T022A−A158E、N062E−Y209E、N062E−H249R、S101A−R186H、E089P−P129E、P129E−E271F、T22A−L111V−G159E、S101A−S103G−V104L−Y209E、S101A−S103G−V104L−G159E、S101A−S103G−V104L−S188D、S101G−S103A−V104I−G159D、T22A−S103G−G159E、T22A−S128N−E271F−Y209E、T22A−Y209E−E271F、T22A−S101A−Y209E、S101A−Y209E−E271F、T22A−L111V−S128N、T22A−S101A−G159E、S101A−S103G−V104L、T22A−S101A−S103G−V104L、S101A−S103G−V104L、S101G−S103A−V104I、S101A−S103G−V104L−S128N、S103A−V104I−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−V104I−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N248D、N62E−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、N62E−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R、T22A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−S24R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−T253R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T22A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N238R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N76D及びS101G−S103A−V104I−G159E−A232V−Q245R−N248D−E271Fのうちの少なくも3つを含む、少なくとも1種にプロテアーゼ変異体を含み、ここで、この少なくとも1種のプロテアーゼ変異体は、配列番号2のアミノ酸配列を有するB.レンタスのサブチリシンGG36プロテアーゼと比較して、合計正味電荷が0、+1、+2、+3、+4又は+5である。
2R−X24R−X43Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、サブチリシン変異体のアミノ酸位置は、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる。
、L42I、N43R、N43A、G46R、P52F、P52E、P52N、T57R、Q59A、N62E、N62Q、V68A、V68C、T71G、I72C、A74C、L75A、L75F、L75R、N76D、S78R、L82R、P86W、E89P、E89T、E89G、E89H、E89I、E89V、E89W、Y91N、K94N、G100S、S101A、S101N、S101G、S101D、S103G、S103N、V104L、V104I、S106V、S106G、A108I、L111V、E112V、G115K、G115R、N117F、G118I、V121F、S128D、S128F、S128L、S128N、P129E、S144R、L148I、A158E、G159E、S160D、S166D、N185E、N185I、R186H、S188E、S188D、D197F、V203E、Y209S、Y209N、Y209F、Y209T、Y209E、Y209H、Y209G、P210R、S212I、S212F、Y214F、A215N、A215D、A215E、L217E、L217N、T224A、A230E、A231I、Q236F、N238R、N238K、P239K、P239G、P239R、P239S、W241R、S242R、S242L、N243R、V244R、N248I、N248V、H249R、L250I、N252R、T253R、L262D、Y263F、S265F、L267V、L267N、N269I、N269R、E271F、E271I、E271H、E271P、E271T、E271V、E271L及びA272Fからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、かつ任意選択で、S103A、G159D、Q236H、Q245R、N248D及びN252Kからなる群から選択される少なくとも1つの変異を含み、このプロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる。
種の追加の酵素を更に含む。
、A231I、P239R、P239S、W241R、S242R、S242L、N243R、V244R、N248I、H249R、N252R、T253R、E271T、E271V、E271L、E271H、E271F、E271P、A1R、S9A、S212F及びN269Rのうち2つ以上を含み;並びに/あるいは次の変異の組:T022R−S024R、S009A−E271L、N018R−W241R、N018R−G115R、N043R−H249R、G020R−H249R、V004R−H249R、G020R−S024R、N018R−H249R、S009A−G020R、G020R−W241R、S009A−S078R、G020R−G115R、N018R−S024R、S024R−S242R、T022R−G115R、N018R−N043R、G020R−N043R、N018R−S242R、S242R−N269R、N018R−V244R、S024R−N269R、G020R−E271L、S024R−E271L、V004R−S009A、G020R−N269R、A001R−S024R、V244R−E271L、S009A−N018R、W241R−E271L、V004R−S024R、S009A−H249R、S009A−T022R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−S24R、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N252K及びS101G−S103A−V104L−A232V−Q236H−Q245R−N248D−N252Kのうちの1つ以上を含み、上記冷水用プロテアーゼ変異体は、配列番号2のアミノ酸配列を有するB.レンタスのサブチリシンGG36プロテアーゼと比較して、0、+1、+2、+3、+4又は+5の合計正味電荷を有し、上記洗濯洗剤洗浄液は、約3mS/cm〜約30mS/cm、約3.5mS/cm〜約20mS/cm、又は更には約4mS/cm〜約10mS/cmの伝導度を有する。
記載される。封入剤は、一般的には、炭水化物、天然又は合成ゴム、キチン、キトサン、セルロース及びセルロース誘導体、ケイ酸塩、リン酸塩、ホウ酸塩、ポリビニルアルコール、ポリエチレングリコール、パラフィンワックス、及びこれらの組み合わせからなる群から選択される。封入材が炭水化物である場合、典型的には、単糖、オリゴ糖、多糖、及びこれらの組み合わせから選択される。一部の典型的な実施形態では、封入材はデンプンである(例えば、欧州特許第0 922 499号;米国特許第4,977,252号、同第5,354,559号、及び同第5,935,826号を参照されたい)。一部の実施形態では、封入材は、熱可塑性プラスチック、アクリロニトリル、メタクリロニトリル、ポリアクリロニトリル、ポリメタクリロニトリル及びこれらの混合物から製造されるプラスチック製のマイクロスフェア、並びに限定するものではないが、使用が見出される、EXPANCEL(登録商標)(Stockviksverken,Sweden)により供給されるもの、並びにPM 6545、PM 6550、PM 7220、PM 7228、EXTENDOSPHERES(登録商標)、LUXSIL(登録商標)、Q−CEL(登録商標)、及びSPHERICEL(登録商標)(PQ Corp.,Valley Forge,PA)などの市販のマイクロスフェアである。
TICLEAN(登録商標)、OPTIMASE(登録商標)、PROPERASE(登録商標)、PURAFECT(登録商標)、PURAFECT(登録商標)OXP、PURAMAX(商標)、EXCELLASE(商標)、及びPURAFAST(商標)(Genencor);ALCALASE(登録商標)、SAVINASE(登録商標)、PRIMASE(登録商標)、DURAZYM(商標)、POLARZYME(登録商標)、OVOZYME(登録商標)、KANNASE(登録商標)、LIQUANASE(登録商標)、NEUTRASE(登録商標)、RELASE(登録商標)及びESPERASE(登録商標)(Novozymes);BLAP(商標)及びBLAP(商標)変異体(Henkel Kommanditgesellschaft auf Aktien,Duesseldorf,Germany)、並びにKAP(B.アルカロフィルス(B. alkalophilus)サブチリシン;花王株式会社,東京,日本)が挙げられる。様々なプロテアーゼが国際公開第95/23221号、同第92/21760号、米国特許第2008/0090747号、及び米国特許第5,801,039号、同第5,340,735号、同第5,500,364号、同第5,855,625号、米国再発行特許第34,606号、米国特許第5,955,340号、同第5,700,676号、同第6,312,936号、及び同第6,482,628号、並びに他の多様な特許に記載されている。一部の更なる実施形態では、本発明への使用が見出されるメタロプロテアーゼは、限定するものではないが、国際公開第07/044993号に記載の中性のメタロプロテアーゼである。
ーゼ、マンナナーゼ、及び/又は少なくとも1種のセルラーゼなどの酵素の混合物が、本発明に包含される。実際に、これらの酵素の多様な混合物が本発明への使用を見出され得ることは想到される。変異体プロテアーゼ及び1種以上の追加の酵素の濃度は、いずれも独立して約10%までの範囲で変化し、クリーニング組成物の残部はクリーニング助剤からなることも想到される。具体的なクリーニング助剤の選別は、処理される表面、物品、又は布地、並びに使用時(例えば、洗浄洗剤を用いる)のクリーニング条件に所望される組成物の形態を考慮することで容易になされる。
許第2 100 949号を参照されたい)、任意の好適なビルダーが、本発明への使用を見出されることが想到される。
15,705号、同第4,537,706号、同第4,515,707号、同第4,550,862号、同第4,561,998号、同第4,597,898号、同第4,968,451号、同第5,565,145号、同第5,929,022号、同第6,294,514号及び同第6,376,445号を参照されたい)。
は相補的DNA)、DNA(デオキシリボ核酸)、ssDNA(単鎖DNA)、dsDNA(2本鎖DNA)、dNTP(デオキシリボヌクレオチド三リン酸)、RNA(リボ核酸)、MgCl2(塩化マグネシウム)、NaCl(塩化ナトリウム)、w/v(体積対重量)、v/v(体積対体積)、w/w(重量対重量)、g(重さ)、OD(光学密度)、ppm(100万分率)、ダルベッコリン酸緩衝溶液(DPBS)、SOC(2%バクトトリプトン、0.5%バクト酵母抽出物、10mMのNaCl、2.5mMのKCl)、テリフィック培地(TB、12g/Lバクトトリプトン、24g/Lグリセロール、2.31g/L KH2PO4、及び12.54g/L K2HPO4)、OD280(280nmでの光学密度)、OD600(600nmでの光学密度)、A405(405nmでの吸光度)、Vmax(酵素触媒反応の飽和最大速度)、PAGE(ポリアクリルアミドゲル電気泳動)、PBS(リン酸緩衝生理食塩水[150mMのNaCl、10mMのナトリウムリン酸緩衝液、pH 7.2])、PBST(PBS+0.25% TWEEN(登録商標)−20)、PEG(ポリエチレングリコール)、PCR(ポリメラーゼ連鎖反応)、RT−PCR(逆転写PCR)、SDS(ドデシル硫酸ナトリウム)、トリス(トリス(ヒドロキシメチル)アミノメタン)、HEPES(N−[2−ヒドロキシエチル]ピペラジン−N−[2−エタンスルホン酸])、HBS(HEPES緩衝生理食塩水)、トリス−HCl(トリス[ヒドロキシメチル]アミノメタン−塩酸塩)、トリシン(N−[トリス−(ヒドロキシメチル)−メチル]−グリシン)、CHES(2−(N−シクロ−ヘキシルアミノ)エタン−スルホン酸)、TAPS(3−{[トリス−(ヒドロキシメチル)−メチル]−アミノ}−プロパンスルホン酸)、CAPS(3−(シクロ−ヘキシルアミノ)−プロパン−スルホン酸、DMSO(ジメチルスルホキシド)、DTT(1,4−ジチオ−DL−トレイトール)、SA(シナピン酸(s,5−ジメトキシ−4−ヒドロキシケイ皮酸)、TCA(トリクロロ酢酸)、Glut及びGSH(還元グルタチオン)、GSSG(酸化グルタチオン)、TCEP(トリス[2−カルボキシエチル]ホスフィン)、Ci(キュリー)、mCi(ミリキュリー)、μCi(マイクロキュリー)、HPLC(高速液体クロマトグラフィー)、RP−HPLC(逆相高速液体クロマトグラフィー)、TLC(薄層クロマトグラフィー)、MALDI−TOF(マトリックス支援レーザー脱離/イオン化法−飛空時間型)、Ts(トシル)、Bn(ベンジル)、Ph(フェニル)、Ms(メシル)、Et(エチル)、Me(メチル)、Taq(サーマス・アクアチクスDNAポリメラーゼ)、クレノウ(DNAポリメラーゼIラージフラグメント(クレノウ)フラグメント))、EGTA(エチレングリコール−ビス(β−アミノエチルエーテル)N,N,N’,N’−テトラ酢酸)、EDTA(エチレンジアミン五酢酸)、bla(β−ラクタマーゼ又はアンピシリン耐性遺伝子)、HDL(強力液体)、HDD(強力粉末洗剤)、HSG(高起泡顆粒洗剤)、CEE(中央及び東ヨーロッパ)、WE(西ヨーロッパ)、洗剤を参照する際に使用する場合のNA(北アメリカ)、洗剤を参照する際に使用する場合の日本及びJPN(日本)、MJ Research(MJ Research,Reno,NV)、Baseclear(Baseclear BV,Inc.,Leiden,the Netherlands)、PerSeptive(PerSeptive Biosystems,Framingham,MA)、ThermoFinnigan(ThermoFinnigan,San Jose,CA)、Argo(Argo BioAnalytica,Morris Plains,NJ)、Seitz EKS(SeitzSchenk Filtersystems GmbH,Bad Kreuznach,Germany)、Pall(Pall Corp.,East Hills,NY and Bad Kreuznach,Germany)、Spectrum(Spectrum Laboratories,Dominguez Rancho,CA)、Molecular Structure(Molecular Structure Corp.,Woodlands,TX)、Accelrys(Accelrys,Inc.,San Diego,CA)、Chemical Computing(Chemical Computing Corp.,Montreal,Canada)、New Brunswick(New Brunswick Scientific,Co.,Edison,NJ)、CFT(Center for Test Materials,Vlaardingen,the Netherlands)、P&G and Procter & Gamble(Procter & Gamble,Inc.,Cincinnati,OH)、GE Healthcare(GE Healthcare,Chalfont St.Giles,United Kingdom)、DNA2.0(DNA2.0,Menlo Park,CA)、OXOID(Oxoid,Basingstoke,Hampshire,UK)、Megazyme(Megazyme International Ireland Ltd.,Bray Business Park,Bray,Co.,Wicklow,Ireland)、Finnzymes(Finnzymes Oy,Espoo,Finland)、Kelco(CP Kelco,Wilmington,DE)、Corning(Corning Life Sciences,Corning,NY)、(NEN(NEN Life Science Products,Boston,MA)、Pharma AS(Pharma AS,Oslo,Norway)、Dynal(Dynal,Oslo,Norway)、Bio−Synthesis(Bio−Synthesis,Lewisville,TX)、ATCC(American Type Culture Collection,Rockville,MD)、Gibco/BRL(Gibco/BRL,Grand Island,NY)、Sigma(Sigma Chemical Co.,St.Louis,MO)、Pharmacia(Pharmacia Biotech,Piscataway,NJ)、NCBI(National Center for Biotechnology Information)、Applied Biosystems(Applied Biosystems,Foster City,CA)、BD Biosciences及び/又はClontech(BD Biosciences CLONTECH Laboratories,Palo Alto,CA)、Operon Technologies(Operon Technologies,Inc.,Alameda,CA)、MWG Biotech(MWG Biotech,High Point,NC)、Oligos Etc(Oligos Etc.Inc,Wilsonville,OR)、Bachem(Bachem Bioscience,Inc.,King of Prussia,PA)、Difco(Difco Laboratories,Detroit,MI)、Mediatech(Mediatech,Herndon,VA、Santa Cruz(Santa Cruz Biotechnology,Inc.,Santa Cruz,CA)、Oxoid(Oxoid Inc.,Ogdensburg,NY)、Worthington(Worthington Biochemical Corp.,Freehold,NJ)、GIBCO BRL又はGibco BRL(Life Technologies,Inc.,Gaithersburg,MD)、Millipore(Millipore,Billerica,MA)、Bio−Rad(Bio−Rad,Hercules,CA)、Invitrogen(Invitrogen Corp.,San Diego,CA)、NEB(New England Biolabs,Beverly,MA)、Sigma(Sigma Chemical Co.,St.Louis,MO)、Pierce(Pierce Biotechnology,Rockford,IL)、Takara(Takara Bio Inc.Otsu,Japan)、Roche(Hoffmann−La Roche,Basel,Switzerland)、EM Science(EM Science,Gibbstown,NJ)、Qiagen(Qiagen,Inc.,Valencia,CA)、Biodesign(Biodesign Intl.,Saco,Maine)、Aptagen(Aptagen,Inc.,Herndon,VA)、Sorvall(Sorvall brand,from Kendro Laboratory Products,Asheville,NC)、Molecular Devices(Molecular Devices,Corp.,Sunnyvale,CA)、R&D Systems(R&D Systems,Minneapolis,MN)、Siegfried Handel(Siegfried Handel AG,Zofingen,Switzerland)、Stratagene(Stratagene Cloning Systems,La Jolla,CA)、Marsh(Marsh Biosciences,Rochester,NY)、Geneart(Geneart GmbH,Regensburg,Germany)、Bio−Tek(Bio−Tek Instruments,Winooski,VT)、(Biacore(Biacore,Inc.,Piscataway,NJ)、PeproTech(PeproTech,Rocky Hill,NJ)、SynPep(SynPep,Dublin,CA)、New Objective(New Objective brand、Scientific Instrument Services,Inc.,Ringoes,NJ)、Waters(Waters,Inc.,Milford,MA)、Matrix Science(Matrix Science,Boston,MA)、Dionex(Dionex,Corp.,Sunnyvale,CA)、Monsanto(Monsanto Co.,St.Louis,MO)、Wintershall(Wintershall AG,Kassel,Germany)、BASF(BASF Co.,Florham Park,NJ)、Huntsman(Huntsman Petrochemical Corp.,Salt Lake City,UT)、Shell Chemicals(Shell Chemicals,Inc.,London,UK)、Stepan(Stepan,Northfield,IL)、Clariant(Clariant,Sulzbach,Germany)、Industrial Zeolite(Industrial Zeolite Ltd.,Grays,Essex,UK)、Jungbunzlauer(Jungbunzlauer,Basel,Switzerland)、Solvay(Solvay,Brussels,Belgium)、3V Sigma(3V Sigma,Bergamo,Italy)、Innospec(Innospec,Ellesmere Port,UK)、Thermphos(Thermphos,Vlissiggen−Ost,the
Netherlands)、Ciba Specialty(Ciba Specialty Chemicals,Basel,Switzerland)、Dow Corning(Dow Corning,Barry,UK)、Enichem(Enichem Iberica,Barcelona,Spain)、Fluka Chemie AG(Fluka Chemie AG,Buchs,Switzerland)、Gist−Brocades(Gist−Brocades,NV,Delft,the Netherlands)、Dow Corning(Dow Corning Corp.,Midland,MI)、Mettler−Toledo(Mettler−Toledo Inc,Columbus,OH)、RB(Reckitt−Benckiser,Slough,UK)、及びMicrosoft(Microsoft,Inc.,Redmond,WA)。
ムグラフトコポリマーは、ポリエチレンオキシド主鎖と複数のポリビニルアセテート側鎖とを有する、ポリビニルアセテートグラフト化ポリエチレンオキシドコポリマーである。ポリエチレンオキシド主鎖の分子量は約6000であり、ポリ酢酸ビニルに対するポリエチレンオキシドの重量比は約40:60であり、エチレンオキシド単位50個当たりグラフト点は1個以下である。
液)を含有している100mMのトリス緩衝液(pH 8.6)で希釈した。トリス/Ca緩衝液で、既知の濃度のエグリンc原液の希釈物もいくつか調製した。各希釈エグリンc溶液のアリコートを、等量のサブチリシン変異体溶液と混合した。混合溶液を室温で15〜30分インキュベートし、次いで各サンプルのプロテアーゼ活性をAAPFアッセイにより測定した。各エグリンcサンプル及び既知の濃度のエグリンcの添加に基づくプロテアーゼ活性の減少を観察することで、各サブチリシン酵素変異体を完全に阻害するのに必要とされるエグリンc濃度を算出した。この濃度はサンプル中の酵素濃度と等価である。同様に、エグリンcは不含の、トリス/Ca緩衝液のみのアリコートを各サブチリシン変異体サンプルと混合し、エグリンcの非存在下でのプロテアーゼ活性をAAPFアッセイにより測定した。次いでサブチリシン変異体の比活性を、上記のように測定した酵素濃度を用い算出した。
)円形ダイを用い、切り出す。最終的には2枚のマイクロスウォッチを、表面積全体を曝露させるために96ウェルMTPの各ウェルに垂直に配置する(すなわち、ウェルの底に平らに配置することはない)。
示され、プロペプチドは下線の引かれている小文字で示され、及びGG36成熟配列は大文字で示される)は以下に提供されるものである:
熱した後、続いて94℃で15秒の変性、55℃で15秒のアニーリング、及び72℃で2分の伸長を30サイクル行った。増幅させた後、各変異体につき2〜4つのPCRフラグメント(表4−3)をQIAGEN(登録商標)ゲルバンド精製用キットを用いゲルから精製し、混合した(各フラグメントにつき50ng)。完全長の遺伝子フラグメントを生成するためにプライマーP5954及びP5955を用い伸長PCRする際、これらの混合物をDNAテンプレートとして使用した。伸長工程を72℃で2分にわたって実施したことを除き、PCR条件は上記の条件と同様のものであった。完全長のDNAフラグメントをQIAGEN(登録商標)ゲルバンド精製用キットを用いてゲルから精製し、制限酵素BamHI及びHindIIIを用いて消化し、同様の制限酵素で消化したpHPLT−GG36でライゲーションした。Illustra Templiphiキットでローリングサークル型増幅法を用い、1マイクロリットルのライゲーション混合物を製造元(GE Healthcare)からの取扱説明書に従って増幅させることで、バチルス・サブチルスに形質転換させるための多量体DNAを生成した。ローリングサークル型増幅産物を100倍希釈し、B.サブチリス細胞の形質転換に用いた(遺伝子型:ΔaprE,ΔnprE,amyE::xylRPxylAcomK−phleo)。形質転換混合物のアリコートを、1.6%のスキムミルク及び10μg/mLのネオマイシンを含有しているLBプレートに蒔き、37℃で一晩インキュベートした。続いて、ハローを生じたコロニーを、プラスミドDNAを抽出するため(QIAprep Spinミニプレップキット、Qiagen)10μg/mLのネオマイシンを含有している120μLのルリアブロス培地に接種した。抽出したプラスミドを、配列決定して、所望の変異が存在しているか確認した。表4−4に示される伸長PCRによる変異体生成。
−N43R−H249R、G20R−T22R−N43R、G20R−N43R−S242R、G20R−N43R−E271L、G20R−N43R−V244R、G20R−S24R−N43R−S242R、S9A−T22R−S78R−S212F−W241R、S9A−G20R−N43R−S212F、S9A−N43R−S212F、G20R−N43R−S212F、G20R−T22R−N43R−S212F、S24R−S78R−S212F、S9A−N43R−S78R、S9A−N43R−S78R−S242R、S9A−G20R−N43R−S78R、G20R−S24R−N43R−S78R−S242R、T22R−S24R−S78R−S212F、S9A−G20R−N43R−S78R−S242R、G20R−N43R−S78R−H249R、G20R−N43R−S78R、S9A−S78R−S212F、S9A−T22R−N43R−S78R、S9A−G20R−S24R−N43R、S9A−T22R−S78R−S212F、V4R−S9A−T22R−S78R−S212F、G20R−S24R−N43R、A1R−S9A−N43R、G20R−S24R−N43R−G115R、S9A−S24R−N43R、G20R−T22R−S24R−N43R、A1R−S24R−N43R、S9A−G20R−S24R−N43R−S242R、S9A−G20R−T22R−S78R−S212F、S9A−S24R−N43R−V244R、S9A−S24R−N43R−S242R、V4R−S9A−T22R−S24R−S212F、及びT22R−S24R−N43Rを包含する(BPN’番号に対応する)。
N238K、N238L、P239K、P239G、P239R、P239H、P239T、P239N、P239S、P239F、S240R、W241R、S242L、S242R、N243F、N243R、V244R、Q245R、I246S、N248D、N248V、N248I、N248R、H249R、H249T、L250I、K251R、K251S、N252I、N252F、N252R、N252K、N252H、T253I、T253R、T253F、A254C、S256N、G258R、T260V、T260I、L262D、L262H、Y263F、S265F、L267V、L267N、L267M、N269I、N269R、A270C、E271I、E271V、E271H、E271M、E271L、E271P、E271A、E271F、E271T、A272F、A272F、A272R、A273F、A273I、及びT274G。変異体及びライブラリは実施例11に記載のようにDNA 2.0,Inc.に外注し構築した。作製された変異体はこれらの変異を1つ以上含有しており、この変異体を、BMIマイクロスウォッチクリーニングアッセイ(実施例1)及び表1−2に記載の洗剤組成物で冷水クリーニングについて試験した。
Claims (116)
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつG020R−N043R、N062E−A158E、S103G−A158E、S128N−A158E、A016S−A158E、V104L−A158E、E089P−A158E、L111V−A158E、T022A−A158E、S101A−A158E、L148I−A158E、P129E−A158E、T022A−E089P、A016S−E089P、N062E−E089P、N062E−E271F、A158E−E271F、R186H−E271F、P129E−E271F、L111V−E271F、Y209E−E271F、A016S−E271F、S188D−E271F、T022A−E271F、G159E−E271F、V104L−E271F、S101A−E271F、E089P−E271F、S128N−E271F、S103G−E271F、L148I−E271F、H249R−E271F、N062E−G159E、A016S−G159E、S128N−G159E、L148I−G159E、L111V−G159E、E089P−G159E、T022A−G159E、P129E−G159E、S103G−G159E、V104L−G159E、A158E−G159E、S101A−G159E、A158E−H249R、L111V−H249R、P129E−H249R、N062E−H249R、A016S−H249R、R186H−H249R、L148I−H249R、G159E−H249R、S101A−H249R、S188D−H249R、V104L−H249R、Y209E−H249R、T022A−H249R、S128N−H249R、S103G−H249R、E089P−H249R、T022A−L111V、S101A−L111V、A016S−L111V、V104L−L111V、N062E−L111V、S103G−L111V、E089P−L111V、A016S−L148I、N062E−L148I、T022A−L148I、P129E−L148I、V104L−L148I、S103G−L148I、S128N−L148I、S101A−L148I、E089P−L148I、L111V−L148I、A016S−N062E、T022A−N062E、N062E−P129E、T022A−P129E、S128N−P129E、A016S−P129E、S101A−P129E、V104L−P129E、E089P−P129E、S103G−P129E、L111V−P129E、N062E−R186H、S128N−R186H、S101A−R186H、T022A−R186H、A016S−R186H、A158E−R186H、E089P−R186H、P129E−R186H、G159E−R186H、S103G−R186H、V104L−R186H、L111V−R186H、L148I−R186H、N062E−S101A、T022A−S101A、A016S−S101A、E089P−S101A、N062E−S103G、T022A−S103G、A016S−S103G、S101A−S103G、E089P−S103G、N062E−S128N、A016S−S128N、T022A−S128N、S101A−S128N、V104L−S128N、E089P−S128N、S103G−S128N、L111V−S128N、L111V−S188D、N062E−S188D、A016S−S188D、L148I−S188D、T022A−S188D、S128N−S188D、S101A−S188D、V104L−S188D、E089P−S188D、P129E−S188D、G159E−S188D、R186H−S188D、S103G−S188D、A158E−S188D、A016S−T022A、A016S−V104L、T022A−V104L、S101A−V104L、N062E−V104L、S103G−V104L、E089P−V104L、G159E−Y209E、L111V−Y209E、S101A−Y209E、A016S−Y209E、S128N−Y209E、L148I−Y209E、P129E−Y209E、N062E−Y209E、T022A−Y209E、S103G−Y209E、A158E−Y209E、S188D−Y209E、V104L−Y209E、E089P−Y209E、R186H−Y209E、N018R−W241R、G020R−W241R、S024R−W241R、S009A−W241R、G020R−W241R、V004R−W241R、N043R−W241R、S078R−W241R、T022R−W241R、G115R−W241R、A001R−W241R、S212F−W241R、L082R−W241R、N018R−V244R、S024R−V244R、S078R−V244R、G020R−V244R、S212F−V244R、S009A−V244R、L082R−V244R、A001R−V244R、N043R−V244R、T022R−V244R、V004R−V244R、G115R−V244R、W241R−V244R、S242R−V244R、A001R−V004R、S009A−T022R、N018R−T022R、G020R−T022R、V004R−T022R、A001R−T022R、S024R−S242R、N018R−S242R、V004R−S242R、G020R−S242R、S212F−S242R、L082R−S242R、S078R−S242R、A001R−S242R、S009A−S242R、T022R−S242R、G115R−S242R、N043R−S242R、W241R−S242R、N018R−S212F、T022R−S212F、V004R−S212F、S024R−S212F、A001R−S212F、G115R−S212F、G020R−S212F、S009A−S212F、N043R−S212F、S078R−S212F、L082R−S212F、S009A−S078R、G020R−S078R、S024R−S078R、T022R−S078R、N018R−S078R、V004R−S078R、A001R−S078R、N043R−S078R、T022R−S024R、G020R−S024R、N018R−S024R、A001R−S024R、V004R−S024R、S009A−S024R、V004R−S009A、A001R−S009A、S242R−N269R、S024R−N269R、G020R−N269R、T022R−N269R、H249R−N269R、S212F−N269R、N043R−N269R、V244R−N269R、A001R−N269R、N018R−N269R、S078R−N269R、S009A−N269R、G115R−N269R、W241R−N269R、V004R−N269R、L082R−N269R、N018R−N043R、G020R−N043R、V004R−N043R、T022R−N043R、S009A−N043R、A001R−N043R、S024R−N043R、S009A−N018R、V004R−N018R、A001R−N018R、S024R−L082R、S009A−L082R、N018R−L082R、A001R−L082R、S078R−L082R、G020R−L082R、T022R−L082R、V004R−L082R、N043R−L082R、N043R−H249R、G020R−H249R、V004R−H249R、N018R−H249R、S009A−H249R、S212F−H249R、T022R−H249R、S024R−H249R、G115R−H249R、A001R−H249R、L082R−H249R、S242R−H249R、W241R−H249R、V244R−H249R、S078R−H249R、N018R−G115R、G020R−G115R、T022R−G115R、S078R−G115R、S009A−G115R、V004R−G115R、A001R−G115R、L082R−G115R、N043R−G115R、S024R−G115R、S009A−G020R、N018R−G020R、V004R−G020R、A001R−G020R、S009A−E271L、G020R−E271L、S024R−E271L、V244R−E271L、W241R−E271L、N043R−E271L、T022R−E271L、H249R−E271L、S212F−E271L、G115R−E271L、S242R−E271L、S078R−E271L、V004R−E271L、N269R−E271L、A001R−E271L、N018R−E271L、及びL082R−E271Lから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタス(Bacillus lentus)のサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンス(Bacillus amyloliquefaciens)のサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつG020R−N043R、G020K−N062E、S024F−N116L、G020K−S024F、S024R−A174T、S024R−G118R、S024R−K235F、S024R−P086R、S024R−P086W、S078R−G118R、T033S−G118R、T033S−K235F、Y209A−W241R、G020R−N076D、N018R−Q245R、S024R−R045T、A232V−Q245R、G118R−A172V、G118R−A194T、I008T−S024R、K235F−N243F、N018R−S103A、N018R−V104I、P086W−G118R、P086W−N243F、P086W−Y209A、S024C−T033S、S024R−A232V、S024R−N243F、S024R−P239Q、S024R−S101G、S024R−S141G、S024R−T033S、S024R−T274I、S024R−Y209A、S078R−P086W、S101G−A232V、T033S−L148F、T033S−P086W、T033S−P201S、T033S−S078R、T033S−W241R、T033S−Y209A、A230E−H249R、A232V−H249R、G118R−K235F、N076D−Q245R、P086W−K235F、S024R−R247H、S024R−V104A、S078R−K235F、S101G−H249R、S103A−A232V、T033S−A048T、T033S−P239T、T033S−T253A、T143A−Y209A、Y209A−K235F、N018R−R045T、Y209A−N243F、S024R−A272P、S024R−R269C、S101G−V104I、V104I−A232V、N076D−H249R、及びS024R−N076Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼ
の合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつG020R−N076D、S024R−R045T、A230E−H249R、N018R−R045T、N018R−Q245R、S101G−A232V、S024R−A232V、A232V−Q245R、S024R−S101G、N018R−V104I、N018R−S103A、S101G−H249R、A232V−H249R、S103A−A232V、N076D−Q245R、S101G−V104I、V104I−A232V、N076D−H249R、S024R−N076D、S024F−N116L、G020K−S024F、G020K−N062E、T033S−G118R、S024R−P086W、S024R−G118R、S024R−P086R、Y209A−W241R、S024R−W241R、S024R−K235F、G118R−Y209A、S078R−G118R、T033S−K235F、S024R−A174T、P086W−Y209A、I008T−S024R、P086W−G118R、T033S−W241R、S024R−N243F、S024R−Y209A、T033S−P086W、S024R−T033S、P086W−N243F、T033S−P201S、S024R−P239Q、S078R−P086W、K235F−N243F、G118R−A172V、T033S−L148F、T033S−S078R、T033S−N243F、S024C−T033S、G118R−A194T、T033S−Y209A、S024R−S141G、S024R−T274I、P086W−K235F、A015T−T033S、Y209A−K235F、S024R−R247H、S078R−K235F、S024R−V104A、T033S−A048T、G118R−K235F、T033S−T253A、T143A−Y209A、T033S−P239T、Y209A−N243F、S024R−A272P、及びS024R−R269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつG020K−G023A−N043W−G118R−S128I−P129E−G159D−S188D、G020K−G023A−N062E−N116L、G020K−G023A−N062E−N116L−S188D、G020K−G023A−N062E−N116L−S188D−T213A、G020K−G100S−N116L−A158E−S166D−N243F、G020K−N043W−N062E−N116L−S188D、G020K−N062E、G020K−N062E−N116L、G020K−N062E−N116L−S188D、G020K−N062E−N116L−T213A、G020K−N062E−S188D−T213A、G020K−S024F−N062E−N116L−G118R−S188D、G020K−S024F−N062E−N116L−S188D、G020K−S024F−N062E−S188D−T213A、G023A−N062E−N116L−S188D、G023A−S024F−N062E−N116L−T213A、N043R−N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、N043W−N062E−N116L、N043W−S101D−S212M−N243F、N062E−N116L−G118R−S188D、N062E−N116L−G118R−T213A、N062E−N116L−S188D−T213A、S024F−G118R−S128I−P129E−G159D、S024F−N062E−N116L−S188D、S024R−S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101D−S103N−N116L−S144R−A215D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N043R−S101G−S103A−V104I−G159D−S188D−L217E−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−S128I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−S101G−S103A−V104I−G159D−L217E−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022L−T038F−A048R−N062E−G100S−R186K、T033S−N043W−N218D−P239G−N243F、V026F−A048R−S105T−T213A−N218D−T224A、V026F−L031F−S078N−G102A−S160D、V026F−V051W−V104L−S106E、V104L−S105T−T213A−L217E−S256N、A016S−N062E−A158E−H249R、A016S−N062E−A158E−R186H−E271F、A016S−N062E−A158E−R186H−H249R、A016S−N062E−V104L−A158E−R186H−E271F、A016S−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、G020K−G023A−N062E−S188D、G020K−G023A−S024F−N062E−G118R−S188D−T213A、G020K−N043W−N062E−N116L−S188D−T213A−P239G、G020K−S024F−N062E−S188D−P239G、G023A−N062E−N116L−G118R、G023A−N062E−N116L−G118R−S188D−P239G、G023A−S024F−N062E−N116L−G118R、H017R−T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N062E−A158E−G159E−H249R、N062E−A158E−H249R、N062E−A158E−R186H−E271F、N062E−A158E−R186H−H249R、N062E−A158E−R186H−H249R−E271F、N062E−A158E−S188D−H249R、N062E−A158E−S188D−H249R−E271F、N062E−G159E−H249R、N062E−G159E−H249R−E271F、N062E−G159E−R186H−H249R、N062E−G159E−S188D−H249R、N062E−R186H−S188D−H249R−E271F、N062E−S101A−A158E−H249R、N062E−S101A−A158E−R186H−E271F、N062E−S101A−A158E−R186H−H249R−E271F、N062E−S101A−G159E−H249R、N062E−S101A−R186H−H249R、N062E−S101A−S188D−H249R、N062E−S101A−S188D−H249R−E271F、N062E−S101A−V104L−A158E−R186H−E271F、N062E−S128N−A158E−G159E−E271F、N062E−V104L−A158E−S188D−H249R−E271F、N076D−S101G−S103A−V104I−A232V−M222Q−Q245R、S024F−N062E−N116L−P239G、S024F−N062E−S188D−T213A、S024F−N116L、S024R−N043R−N076D−S101A−S103A−V104I−A158E−S18
8D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F−E271F、S101A−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S128N−A158E−R186H−E271F、S101A−S128N−A158E−Y209E−H249R、S101A−V104L−A158E−R186H−S188D−H249R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222Q−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A232V−M222Q−Q245R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、S128N−A158E−G159E−E271F、S128N−A158E−H249R、S128N−A158E−R186H−E271F、S128N−A158E−R186H−H249R、S128N−A158E−R186H−S188D−E271F、S128N−A158E−S188D−E271F、S128N−A158E−S188D−H249R、S128N−A158E−S188D−Y209E−E271F、S128N−A158E−Y209E−、T022A−N043R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N062E−A158E、T022A−S024R−S101D−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S024R−S103A−V104I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S128N−A158E−H249R、V104L−S128N−A158E−H249R、V104L−S128N−A158E−R186H−E271F、V104L−S128N−A158E−R186H−H249R、及びV104L−S128N−A158E−S188D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+
5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつA016S−N062E−A158E−H249R−E271F、A016S−N062E−S128N−R186H−E271F、A016S−N062E−V104L−R186H−S188D−E271F、A016S−S101A−S128N−R186H、A016S−S128N−A158E−R186H、A016S−V104L−A158E−R186H−E271F、A016S−V104L−S188D−H249R、A158E−R186H−H249R、A158E−R186H−S188D−H249R−E271F、G020K−G023A−N116L−S188D、G020K−G023A−S024F−N062E−N116L−S188D−T213A、G020K−N043W−N062E−N116L−P239G、G020K−S024F−N043W−N062E−N116L−T213A、G020K−S024F−N062E、G023A−N043W−N062E−N116L−G118R−T213A、G023A−T038F−S078N−G100S−S212M−A215D、G100S−N116L−A158E−T213A、G102A−S103N−S105T−A194E、H017R−T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、N043W−N062E−N116L−S188D、N062E−A158E−H249R−E271F、N062E−A158E−R186H−S188D−H249R、N062E−L148I−G159E、N062E−N116L−S188D、N062E−R186H−H249R、N062E−S078N−G102A−N116L−S144R−L250I、N062E−S101A−A158E−R186H−H249R、N062E−S101A−A158E−S188D−H249R、N062E−S101A−R186H、N062E−S101A−R186H−E271F、N062E−S101A−R186H−H249R−E271F、N062E−S101A−R186H−S188D−E271F、N062E−S101A−R186H−S188D−H249R、N062E−S101A−V104L−R186H−S188D−E271F、N062E−S128N−A158E、N062E−S128N−G159E−H249R、N062E−S188D−P239G、N062E−V104L−G159E−H249R、N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A114V−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A232V−M222S−Q245R、S024F−A048R−G118R−S166D−L217E、S024F−N062E−N116L、S024F−N062E−N116L−T213A−P239G、S024F−N062E−S188D−P239G、S024F−S101D−G118R−A215D−L250I−A272F、S024R−K027R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、S078N−V104L−G118R−S128D、S101A−A158E−R186H−H249R、S101A−A158E−R186H−S188D−H249R、S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、S101A−S103G−A158E−R186H−H249R、S101A−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−G159E−A232V−Q245R−N248D−H249R、S101A−S128N−A158E−H249R、S101A−S128N−A158E−S188D−Y209E−E271F、S101A−S128N−A158E−Y209E、S101A−S128N−P129E−R186H−H249R、S101A−V104L−A158E−R186H−H249R、S101A−V104L−A158E−R186H−S188D−E271F、S101A−V104L−S128N−A158E−R186H−E271F、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−A232V−M222S−Q245R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−S130A−A158E−N183D−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101S−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N043R−N062E−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T
022A−N043R−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−N043R−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S024R−N043R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S024R−S101D−S103A−V104I−G118R−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S101A−A158E−R186H−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D、T022A−S103A−V104I−G159D−S188D−A232V−N248D、T022L−L031F−G102A−S128D−T224A−N243F、T022L−T038F−V121F−S160D−A272F、V026F−S078N−G159C−R186K−N243F、V104L−A158E−H249R、V104L−A158E−R186H−H249R、V104L−A158E−R186H−H249R−E271F、V104L−A158E−R186H−S188D−H249R、V104L−A158E−R186H−S188D−H249R−E271F、V104L−A158E−S188D−H249R−E271F、V104L−S128N−A158E−R186H−S188D−E271F、V104L−S128N−G159E−E271F、V104L−S128N−R186H−S188D−H249R、及びV121F−N185E−T224A−P239Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、プロテアーゼ変異体のアミノ酸位置は、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつG118R−Y209A、G118R−Y209A−N243F、L021M−S024R−T033S、P005S−S078R−G118R−W241R、P086W−G118R−A133V、P086W−G118R−N243F、P086W−G118R−Y209A、P086W−Y209A−N243F、S024R−A174T、S024R−G118R、S024R−G118R−Y209A、S024R−G118R−Y209A−K235F、S024R−G118R−Y209A−N243F、S024R−K235F、S024R−P086R、S024R−P086S−S141G、S024R−P086W、S024R−P086W−G118R、S024R−P086W−G118R−V203I、S024R−P086W−N243F、S024R−P086W−Y209A、S024R−S078R−P086W、S024R−S078R−P086W−G118R−A270T、S024R−S078R−P086W−N243F、S024R−T033S−A133V、S024R−T033S−G118R、S024R−T033S−P086S−S085N−K235F、S024R−T033S−P086S−S087N−Y209A、S024R−T033S−P086W、S024R−T033S−P086W−G118R、S024R−T033S−S078R−P086W、S024R−T033S−S078R−P086W−G118R、S024R−T033S−S078R−Y209A、S024R−T033S−W241R、S024R−T033S−Y209A−K235F、S024R−Y209A−W241R、S078R−G118R、S078R−P086W−K235F、S078R−P086W−N243F、S078R−P086W−Y209A、S078R−Y209A−K235F、T033S−A172V−Y209A、T033S−G118R、T033S−G118R−G159D−Y209A、T033S−G118R−N243F、T033S−G118R−W241R、T033S−G118R−Y209A−N243F、T033S−K235F、T033S−P086W−G118R、T033S−P086W−G118R−Y209A−N243F、T033S−P086W−N243F、T033S−S078R−P086W、T033S−S078R−P086W−G118R−Y209A、T033S−S078R−Y209A、T033S−Y209A−N243F、Y209A−W241R、A001R−S009A−N043R、A001R−S101G−S103A−V104I−A232V−Q245R、A001T−N018R−S024R−N076D−N116A−T213A−H249R、A194F−G211Q−Q236N、E089I−N116A−N117F−T224A−H249R、G020R−G025R−N116A−Y167W、G020R−H249R−N269R、G020R−N043D−N076D−A230E−H249R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043R−A230E、G020R−N043R−A230E−S242R、G020R−N043R−E271L、G020R−N043R−H249R、G020R−N043R−H249R−E271L、G020R−N043R−N269R、G020R−N043R−R045T−A230E、G020R−N043R−R045T−S101A−N269R、G020R−N043R−R045T−S242R、G020R−N043R−S101A−N116A−T213A−A215F、G020R−N043R−S101A−N269R、G020R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−N043R−S212F、G020R−N043R−S212F−W241R、G020R−N043R−S242R、G020R−N043R−S242R−E271L、G020R−N043R−S242R−H249R、G020R−N043R−V244R、G020R−N043R−W241R、G020R−N062Q−E089I−R186K−S212M、G020R−N076D、G020R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N116A−N269R、G020R−P052N−N062Q−Y091F−Y192W、G020R−Q059A−S144R−Y192W−T224A、G020R−S024R−K27E−N043R−N076D−A230E、G020R−S024R−N043D−H249R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−N043D−S242R、G020R−S024R−N043R−R045T、G020R−S024R−N043R−R045T−H249R、G020R−S024R−N043R−R045T−N116A、G020R−S024R−N043R−R045T−N116A−T213A、G020R−S024R−N043R−R045T−S101A−N269R、G020R−S024R−
N043R−R045T−S101A−T213A、G020R−S024R−N043R−S242R、G020R−S024R−N076D−H249R、G020R−S024R−N116A、G020R−S024R−N116A−A215F、G020R−S024R−N116A−T213A、G020R−S024R−N116A−T213A−A215F、G020R−S024R−P052N−Q059A−S216F、G020R−S024R−R045T−A230E−S242R、G020R−S024R−R045T−N116A−N269R、G020R−S024R−R045T−N269R、G020R−S024R−S101A−A215F、G020R−S024R−S101A−N116A、G020R−S024R−S101G−S103A−V104I−L217E−A232V−Q245R−H249R、G020R−S024R−S242R−H249R、G020R−S024R−T213A、G020R−S024R−T213A−A215F、G020R−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S078R−S101G−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S087D−S101G−S103A−V104I−A232V−Q245R、G020R−S101A−N116A−N269R、G020R−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−G118R−A232V−Q245R、G020R−S101A−S103A−V104L−A232V−Q245R、G020R−S101A−S103A−V104V−A232V−Q245R、G020R−S101A−S103S−V104I−A232V−Q245R、G020R−S101A−S103S−V104V−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、G020R−S101G−S103A−A232V−Q245R、G020R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−V150L−A232V−Q245R、G020R−S101G−S103A−V104L−A232V−Q245R、G020R−S101G−S103A−V104V−A232V−Q245R、G020R−S101G−S103G−V104I−A232V−Q245R、G020R−S101G−S103S−V104I−A232V−Q245R、G020R−S101G−S103S−V104L−A232V−Q245R、G020R−S101G−V104I−T213A−A215F−A232V−Q245R、G020R−S101S−S103A−V104I−A232V−Q245R、G020R−S101S−S103A−V104V−A232V−Q245R、G020R−S101S−S103G−V104I−A232V−Q245R、G020R−S101S−S103G−V104V−A232V−Q245R、G020R−S101S−S103S−V104I−A232V−Q245R、G020R−S101S−S103S−V104L−A232V−Q245R、G020R−S101S−S103S−V104V−A232V−Q245R、G020R−S103N−S216F−Q236N−N252R、G020R−S144R−N185I−L233C−Q236N、G020R−S212F−H249R、G020R−S242R−N269R、G020R−T022R−E271L、G020R−T022R−N043R、G020R−T022R−N043R−S212F、G020R−T022R−N043R−W241R、G020R−T022R−S024R−S242R、G020R−T022R−S078R−S242R、G020R−T022R−S078R−W241R、G020R−T022R−S212F−W241R、G020R−T022R−S242R、G020R−T022R−W241R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116S−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T038A−N043R−S101A、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A232V、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T22W−S103A−V104I−A232V−Q245R、G023A−P052N−S144R−Y192W−S216F、G023A−P052N−Y192W−I198L−N252R、G023A−S024R−N117F−S212M−S216F、G023A−S078R−S216F−Q236N−H249R、G023A−Y091F−S101A−I198L−N252R、G023A−Y091F−V121F−Y192W−Q236N、G025R−E089I−N116A−P239S−A270C、G025R−G046R−V121F、G025R−N043A−E089I−N117F、G025R−S103N−R186K−A194F−T224A、G046R−A194F−S212M、G046R−E089I−Y091F−S101A−N116A、G046R−E089I−Y192W−L233C−A270C、G046R−N183D−N238L、G046R−Q059A−S103N−G211Q−S212M、G046R−Q059A−S106G−L217E−H249R、L148I−T213A−N252R、N018R−G020R−N043D、N018R−G020R−N043D−A230E−S242R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−R045T−A230E、N018R−G020R−N043R−N076D−H249R、N018R−G020R−N043R−N076D−S242R−H249R、N018R−G020R−N043R−R045T−S242R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−R045T、N018R−G020R−S024R−N043D−R045T−L233I−S242R、N018R−G020R−S024R−N043R−R045T−N076D−A230E、N018R−G020R−S024R−N076D−S087D−H249R、N018R−G020R−S024R−N076D−V150L−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−N076D−A230E、N018R−N043R−R045T−H249R、N018R−N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−R045T−S242R−H249R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−S242R−H249R、N018R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−
N076D−S101G−V104I−A232V−Q245R、N018R−Q245R、N018R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−A230E、N018R−S024R−N043D−N076D−H249R、N018R−S024R−N043D−N076D−H249R−N269R、N018R−S024R−N043D−N076D−S078R−H249R、N018R−S024R−N043D−R045T−H249R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N043R−N076D−H249R、N018R−S024R−N043R−N076D−H249R−N269R、N018R−S024R−N043R−N076D−S087D−H249R、N018R−S024R−N043R−N076D−V150L−H249R、N018R−S024R−N076D−G211Q−A215F−H249R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−H249R、N018R−S024R−N076D−H249R−N269R、N018R−S024R−N076D−N116A−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N018R−S024R−N076D−S078R−H249R、N018R−S024R−N076D−S078R−S087D−H249R、N018R−S024R−N076D−S078R−V150L−H249R、N018R−S024R−N076D−S087D−H249R−N269R、N018R−S024R−N076D−S087D−S242R−H249R、N018R−S024R−N076D−S087D−V150L−H249R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−S024R−N076D−S242R−H249R、N018R−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−V104I−H249R、N018R−S024R−N076D−V150L−H249R、N018R−S024R−R045T−S242R、N018R−S024R−S101G−V104I、N018R−S024R−S101G−V104I−A232V、N018R−S024R−S242R、N018R−S024R−V104I−H249R、N018R−S024R−V244R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−Q245R、N018R−S101G−S103A−H249R、N018R−S101G−S103A−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−S101G−V104I−A232V−H249R、N018R−S101G−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、N018R−S103A−A232V−H249R、N018R−S103A−V104I−H249R、N018R−T022R−S024R−N043D−N076D−H249R、N018R−T022R−S024R−N043R−N076D−H249R、N018R−T022R−S024R−N076D−H249R、N018R−T022R−S024R−N076D−S087D−H249R、N018R−T022R−S024R−N076D−V150L−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−T22K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−V104I−A232V−H249R、N043A−N062Q−A194F−G211Q、N043A−T057R−N117F−S144R−N183D、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−R045T−N076D−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S242R−H249R、N043R−N116A−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101A−N116A−A215F−N269R、N043R−S101A−N116A−N269R、N043R−S101A−N116A−T213A−A215F−N269R、N043R−S101A−N269R、N043R−S101A−T213A−N269R、N043R−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−A232V−Q245R−E271L、N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−A232V−S242R−Q245R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R、N043R−S242R−H249R、N043R−T213A−A215F−N269R、N062Q−S103N−N117F−A194F、N062Q−S103N−V121F−S144R−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S103A−V104I−Q109R、N076D−S103A−V104I−Q109R−Q245R、N076D−S103A−V104I−S212P−E271V、N076D−S103A−V104I−S212P−Q245L−E271V、N076D−S87R−S103A−V104I−S212P−E271V、N117F−A194F−T213A−A270C、N117F−T213A−A215F、P052N−S078R−S103N−L148I−T213A、P052N−S103N−N116A−L148I−Y192W、R019H−G020R−T022W−S078R−S101G−S103A−V104I−G211Q−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S009A−G020R−N043R−S212F、S009A−G020R−N043R−W241R、S009A−G020R−S024R−N043R、S009A−N043R−S078R、S009A−N043R−S078R−S242R、S009A−N043R−S212F、S009A−N043R−W241R、S009A−T022R−N043R−S078R、S009A−T022R−S078R−S212F、S009A−T022R−S078R−S212F−W241R、S009A−T022R−S212F−W241R、S024R−A215F−N269R、S024R−A232V−Q245R、S024R−G025R−N183D−Y192W−P239S、S024R−N043A−N117F−A194F−G211Q、S024R−N043D−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−A215F、S024R−N043R−A230E、S024R−N043R−A230E−S242R、S024R−N043R−H249R、S024R−N043R−N076D−H249R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N
116A−A215F、S024R−N043R−N116A−A215F−N269R、S024R−N043R−N116A−N269R、S024R−N043R−N116A−T213A−N269R、S024R−N043R−R045T−N076D−A230E−H249R、S024R−N043R−R045T−N269R、S024R−N043R−R045T−S101A−N116A−A215F−N269R、S024R−N043R−R045T−S101A−N116A−T213A−N269R、S024R−N043R−R045T−S242R、S024R−N043R−R045T−T213A−A215F−N269R、S024R−N043R−S101A−A215F、S024R−N043R−S101A−A215F−N269R、S024R−N043R−S101A−N116A、S024R−N043R−S101A−N116A−A215F−N269R、S024R−N043R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−S242R、S024R−N062Q−V104L−S106G−H249R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−V104I−A232V−Q245R、S024R−N116A−T213A−N269R、S024R−R045T、S024R−R045T−N076D−A230E−S242R−H249R、S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S078R−S212F、S024R−S078R−V104L−N116A−N183D、S024R−S087D−S101G−S103A−V104I−A232V−Q245R、S024R−S101A−H120F−A194F−H249R、S024R−S101A−N269R、S024R−S101G−S103A−V104I−A232V−Q245R、S024R−S101G−S103A−V104I−V150L−A232V−Q245R、S024R−S101G−V104I−Q245R、S024R−S103A−Q245R、S024R−S103A−V104I−A232V−H249R、S024R−S103A−V104I−H249R、S024R−S103A−V104I−Q245R、S024R−Y167W−T224A−H249R、S078R−S087D−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−V150L−A232V−Q245R、S078R−S103N−S106G−Y167W−Q236N、S078R−V104L−T213A−A215F−T224A、S078R−Y091F−V121F−L233C−N252R、S087D−S101G−S103A−V104I−A232V−Q245R−N269R、S087R−S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S099F−S144R−Y167W−N252R、S101A−H120F−Y192W−A215F−T224A、S101A−S103A−V104I−T213A−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−Q245R、S101G−S103A−V104I−A232V−Q245R−E271L、S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−A232V−S242R−Q245R、S101G−S103A−V104I−A232V−V244R−Q245R、S101G−S103A−V104I−G115R−A232V−Q245R、S101G−S103A−V104I−N116A−T213A−A232V−Q245R−N269R、S101G−S103A−V104I−Q109R−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S101G−S103A−V104I−S212F−A232V−Q245R、S101G−S103A−V104I−V150L−A232V−Q245R−H249R、S101G−S103A−V104I−V150L−A232V−Q245R−N269R、S105T−S128N−S144R−L148I−S212M、S106G−N117F−N238L、S144R−G211Q−N238L−P239S−H249R、T022R−N043R−S101G−S103A−V104I−A232V−Q245R、T022R−N076D−S101G−S103A−V104I−A232V−Q245R、T022R−S087D−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−A232V−Q245R、T022W−S078R−Y167W−S212M−A270C、T057R−E089I−I198L、T057R−S099F−S105T−I198L−T213A、T057R−S099F−V121F−N185I−Y192W、T057R−Y167W−H249R、V004R−G020R−H249R、V004R−G020R−N043R、V004R−G020R−S024R、V004R−G020R−S024R−H249R、V004R−G020R−S024R−N043R、V004R−G020R−S024R−N043R−S242R、V004R−G020R−S024R−V244R、V004R−N043R−S101G−S103A−V104I−A232V−Q245R、V004R−S009A−G020R−N043R、V004R−S009A−G020R−N043R−S242R、V004R−S009A−G020R−S024R−S242R、V004R−S009A−G020R−S242R、V004R−S009A−N043R−W241R、V004R−S009A−S024R−N043R−W241R、V004R−S009A−S078R−W241R、V004R−S009A−W241R、V004R−S101G−S103A−V104I−A232V−Q245R、V104L−L217E−T224A−H249R−N252R、V104L−T213A−S216F、V121F−N252R−A270C、Y091F−S099F−S101A−S105T−Y167W、N043R−N076D−A230E−H249R、S024R−N043D−N076D−S242R−H249R、G020R−S024R−N043D−R045T、N043R−N076D−H249R、N043R−R045T−H249R、G020R−N043R−N076D、A230E−H249R、N043D−S242R−H249R、G020R−S024R−N043D−N076D−S242R−H249R、S024R−N043D−S242R−H249R、N018R−N043D−R045T−N076D−S242R−H249R、S024R−N043R−N076D、N018R−G020R−H249R、N018R−G020R−N043R、G020R−S024R−T38I−N043R−R045T−N076D−S242R−H249R、S024R−N043R−N076D−A230E−S242R、N018R−G020R−N043D−R045T−N076D−S242R、N018R−S024R−N043D−A230E−H249R、N018R−N043R−N076D−S242R−H249R、G020R−S024R−K27R−N043D−S242R−H249R、G020R−S242R−H249R、N018R−N043R−R045T−S242R、G020R−N043R−N076D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−G020R−N043R−N076D、N018R−S024R−N043D−S242R、R045T−S242R−H249R、N018R−G020R−N043R−R045T−N076D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつA016S−S128N−R186H−E271F、N076D−S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R−E271G、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−G102A−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、A016S−A158E−H249R、A016S−A158E−H249R−E271F、A016S−A158E−R186H−H249R、A016S−L111V−S188D−、A016S−T022A−A158E−R186H−E271F、A048R−S078N−N116L−N185E−L217E−P239G、A048R−S128D−N185E−P239G、A158E−R186H−H249R−E271F、E089P−S101A−P129E−R186H、G020K−G023A−N043W−N116L−S188D−T213A−P239G、G020K−G023A−N062E−N116L−G118R−T213A、G020K−G023A−S024F−N062E−S188D−T213A−P239G、G020K−K027R−P129E−S166D−P239G、G020K−S024F−
N062E−P239G、G020K−S024F−T033S−P129E−A194E、G023A−G100S−A194E−S212M、G023A−N043W−N116L−G118R−S188D、G023A−S024F−G118R−S188D−P239G、G023A−S024F−K027R−N062E、G023A−S024F−N043W−N062E−N116L−G118R、G023A−S024F−N116L−G118R−S188D−T213A、G023A−S024F−N116L−S188D−P239G、K027R−G100S−G118R−S160D−S188D−N243F、K027R−S101D−S103N−S105T−A272F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、N062E−S078N−N116L−T224A、N062E−V104L−A158E−R186H−S188D−H249R、N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S024F−G102A−R186K−T213A−L217E−N243F、S024F−N043W−G118R−S188D、S024F−N043W−V104L−V121F−P129E、S024F−N116L−G118R−S188D−P239G、S024F−S103N−V104L−G118R−S188D、S024R−N043R−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−N076D−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101A−L111V−P129E、S101A−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−V104L−S128N−A158E−R186H、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S128N−P129E−R186H、T022A−A158E−R186H−H249R−E271F、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S103A−V104I−S128I−G159D−S188D−A232V−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S128N−A158E−R186H、T022A−S128N−R186H−S188D−、T022A−V104L−A158E−H249R、T022A−V104L−R186H−S188D−H249R、T022L−G023A−K027R−S101D−V104L−S216F、T022L−S078N−N116L−P129E−S256N、T022L−S078N−S128D−T213A、T033S−G118R−P129E−A194E−P239G、T033S−S105T−S188D−S216F、V026F−V104L−S256N−A272F、T022A−N043R−S103A−V104I−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S101D−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249R、V104L−L148I−S188D−H249R、S024R−S101A−S103A−V104I−A158E−S166D−S188D−L217E−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、T022A−N043R−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271F、S101A−S103G−V104V−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104V−G159E−A232V−Q245R−N248D−H249R、G023A−S024F−V051W−A158E、K027R−T038F−G102A−N116L、N062E−S078N−S144R−S212M、L031F−N116L−S256N−A272F、T022L−T033S−V104L−N116L−S160D−R186K、S024F−G118R−P129E−R186K−T213A、N043W−S105T−T213A−A215D−S216F、L031F−S105T−R186K−S188D、V026F−A194E−T213A−S256N、S103N−S160D−L250I−S256N、S024R−S101G−S103A−V104I−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−N062E−S103A−V104I−G118R−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−L217D−A232V、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D、T022A−S024R−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、G020K−N043W−S188D−T213A、S024F−N062E−G118R−P239G、G023A−N043W−S188D−T213A、G020K−S024F−N043W−N062E−N116L−G118R−S188D−P239G、G020K−N116L−S188D−P239G、G020K−N043W−N062E−G118R、G020K−N043W−N116L−S188D−T213A、G020K−S024F、G023A−N043W−N116L−P239G、G023A−S024F−N043W−N116L−G118R−S188D−P239G、G020K−G023A−N043W−T213A、及びG023A−S024F−N062E−G118R−T213A−P239Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつS101G−S103A−V104I−A232V−Q236H−Q245R−N252K、S101G−S103A−V104I−A232V−Q245R−N248R、S101G−S103A−V104I−G159R−A232V−Q245R−N248D、A232V−Q2
45R、E089I−N117F−N185I−A215F−L233C、G020R−E089I−L217E、G020R−G023A−V104L−Y192W−L233C、G020R−N043D−R045T−N076D−S242R−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−N043R−N076D−A230E−H249R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N116A−A215F−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−R045T−N116A−N269R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−A215F、G020R−S024R−K27R−N043D−S242R−H249R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S024R−N043R−N076D、G020R−S024R−N043R−R045T−A215F、G020R−S024R−N043R−R045T−N076D−S242R−H249R、G020R−S024R−N043R−R045T−N116A−T213A−A215F、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−T38I−N043R−R045T−N076D−S242R−H249R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q245R−E271G、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S101A−S103G−V104V−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、G020R−S103A−V104I−A232V−Q245R、G020R−S242R−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G025R−N043A−Y091F−I198L−A270C、G025R−S105T−S128N−S144R−A270C、G046R−E089I−S099F−R186K−S212M、G118R−A172V、G118R−A194T、G118R−Y209A−K235F、H017Y−S024R−T033S−P086W、I008T−S024R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、K235F−N243F、N018R−G020R−H249R、N018R−G020R−N043D−H249R、N018R−G020R−N043D−R045T−A230E−S242R、N018R−G020R−N043D−R045T−N076D−S242R、N018R−G020R−N043D−R045T−S240P、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043R、N018R−G020R−N043R−N076D、N018R−G020R−N043R−N076D−A230E−S242R、N018R−G020R−N043R−R045T−N076D−H249R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S242R、N018R−G020R−S024R−N043D−R045T−S242R、N018R−G020R−S024R−N043R−N076D−H249R、N018R−G020R−S024R−N043R−R045T−N076D−H249R、N018R−G
020R−S024R−N076D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−L217E−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−R045T−N076D−S242R−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−N076D−A230E−S242R−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−N076D−S242R−H249R、N018R−N043R−R045T−N076D−A230E−S242R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043R−R045T−N076D−S242R、N018R−N043R−R045T−S242R、N018R−N076D−H249R、N018R−N076D−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−N076D−S101G−V104I−H249R、N018R−N076D−S103A−V104I−H249R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−A230E−H249R、N018R−S024R−N043D−A230E−S242R、N018R−S024R−N043D−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−N076D−S242R−H249R、N018R−S024R−N043D−N076D−V150L−H249R、N018R−S024R−N043D−S242R、N018R−S024R−N043D−S242R−H249R、N018R−S024R−N043R−N076D−L217E−H249R、N018R−S024R−N043R−N076D−S078R−H249R、N018R−S024R−N043R−R045T−A230E−H249R、N018R−S024R−N076D、N018R−S024R−N076D−A232V−H249R、N018R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−S024R−N076D−N116A−T213A−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−H249R、N018R−S024R−N076D−S101A−H249R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−S024R−N076D−S101G−A232V、N018R−S024R−N076D−S103A−A232V−Q245R、N018R−S024R−N076D−T213A−H249R、N018R−S024R−N076D−V104I、N018R−S024R−Q245R、N018R−S024R−R045T−A230E−S242R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−S242R、N018R−S024R−V104I、N018R−S024R−V30S−L31S−D32I−T33Q−G34V−I35F、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S101G−S103A−V104I、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S101G−V104I、N018R−S103A、N018R−S103A−V104I−A232V、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、N018R
−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−T22W−S024R−N076D−T213A−A215F−H249R、N018R−V104I、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、N043D−S101G−S103A−V104I−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R、N062Q−S101A−Q236N−N252R−A270C、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N076D−S101G−S103A−V104I−A232V−S242R−Q245R、P005S−S024R−T033S−N243F、P014L−G020R−S024R−N043R−R045T−S101A−A215F、P052N−V104L−N183D−S216F−H249R、P086W−G118R、P086W−N243F、P086W−Y209A、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、R045T−S242R−H249R、S024C−T033S、S024R−A232V、S024R−G046R−Y091F−V121F、S024R−G118R−K235F、S024R−N043A−S105T−S106G−I198L、S024R−N043D−R045T−S242R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R、S024R−N043D−S242R−H249R、S024R−N043R−N076D、S024R−N043R−N076D−A230E−S242R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−R045T−S242R−H249R、S024R−N043R−S101A−T213A、S024R−N076D−Q245R、S024R−N076D−S101G−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、S024R−N076D−S101G−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S103A−V104I−Q245R、S024R−N076D−V104I−Q245R、S024R−N243F、S024R−P086R−G118R、S024R−P086W−Y209A−K235F、S024R−P239Q、S024R−Q245R−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101G、S024R−S101G−Q245R、S024R−S101G−V104I−H249R、S024R−S103A−A232V、S024R−S103A−M175L−A232V−H249R、S024R−S141G、S024R−T033S、S024R−T033S−A194T、S024R−T033S−G118R−K235F、S024R−T033S−G118R−Y209A、S024R−T033S−K235F、S024R−T033S−S078R−G118R、S024R−T033S−S078R−N243F、S024R−T033S−Y209A、S024R−T033S−Y209A−N243F、S024R−T274I、S024R−V104I−H249R、S024R−V104I−Q245R、S024R−Y091F−I198L−A215F−P239S、S024R−Y209A、S024R−Y209A−K235F、S024R−Y209A−S242P、S078R−P086W、S078R−S099F−N116A−R186K−T224A、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−A232V、S101G−S103A−V104I−A232V−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S101G−S103A−V104I−Q245R、S105T−G211Q−S216F、S106G−N185I−S216F−Q236N、T022R−S101G−S103A−V104I−V150L−A232V−Q245R、T033S−G118D−A138V−Y209A、T033S−G118R−Y209A−、T033S−L148F、T033S−N243F、T033S−P086W、T033S−P201S、T033S−S078R、T033S−W241R、T033S−Y209A、T033S−Y209A−K235F、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、及びV104L−H120F−R186K−S216F−N252Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつA015T−T033S、A016T−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、A230E−H249R、A232V−H249R、E089I−S105T−N116A−A215F−S216F、E089I−Y091F−N185I−G211Q−A270C、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−N043R−N076D、G020R−N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−P052N−S101A−I198L−L233C、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V
−Q245R−N269R、G020R−S024R−N043D−N076D−H249R、G020R−S024R−N043D−N076D−S242R−H249R、G020R−S024R−N043D−R045T−A230E−S242R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S024R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S024R−R045T−N076D−S242R−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022R−N269R、G020R−T022R−S078R−S212F−W241R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−N263S、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、G025R−N062Q−S128N−S144R−N185I、G025R−N116A−H120F−T224A−A270C、G118R−K235F、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−N043D−N076D−S242R−H249R、N018R−G020R−N043D−R045T−N076D−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−N043R−R045T−H249R、N018R−G020R−N043R−R045T−N076D−A230E−H249R、N018R−G020R−N076D、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N043R−N076D、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N1
83D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、N018R−N043D−A230E−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043D−N076D−S242R−H249R、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−N043R−N076D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−N043R−R045T−A230E−S242R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−A232V−H249R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N076D−S101G−I198T−A232V、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−N076D−S101G−V104I、N018R−N076D−S242R、N018R−N076D−S242R−H249R、N018R−N076D−V104I−Q245R−H249R、N018R−R045T−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N043D−N076D−S087D−H249R、N018R−S024R−N043D−N076D−S242R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−A232V、N018R−S024R−N076D−I198L−A215F−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−L217E−H249R−N269R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S087D−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−S024R−N076D−S101A−N116A
−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、N018R−S024R−N076D−S101G、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、N018R−S024R−N076D−S103A−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−V150L−S242R−H249R、N018R−S024R−R045T−A230E−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A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−S101A−I198L−H249R、N018R−V104I−A232V、N043A−Q059A−S101A−S216F−T224A、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S242R−H249R、N043R−A230E−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、N043R−R045T−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R−N269R、N076D−A232V−Q245R、N076D−Q245R、N076D−S101G−A232V−Q245R、N076D−S101G−S103A−Q245R、N076D−S101G−S103A−V104I−A232V−H249R、N076D−S101G−S103A−V104I−H249R、N076D−S101G−S103A−V104I−V150L−A232V−Q245R、N076D−S101G−V104I−H249R、N076D−S101G−V104I−Q245R、N076D−S103A−V104I−A232V−Q245R、N076D−S103A−V104I−Q245R、N076D−V104I−A232V−Q245R、N076D−V104I−Q245R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、P086W−K235F、P086W−Y209A−K235F、Q012H−V104A−G118R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、S024R−G118R−N243F−R269H、S024R−K235F−N243F、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−N076D−A230E−H249R、S024R−N076D−A232V−H249R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N076D−S101G、S024R−N076D−S101G−A232V−H249R、S024R−N076D−S101G−S103A−A232V、S024R−N076D−S101G−S103A−V104I−M175L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S101G−V104I−A232V−H249R、S024R−N076D−S103A−H249R、S024R−N076D−S103A−Q245R、S024R−N076D−S103A−V104I−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−R045T−S242R−A273V、S024R−R247H、S024R−S101G−S103A、S024R−S101G−S103A−A232V、S024R−S101G−S103A−V104I、S024R−S103A−Q245R−H249R、S024R−S103A−V104I、S024R−S106G−N116A−S212M−T224A、S024R−T033S−A151V、S024R−T033S−A174V−K235F、S024R−T033S−A228T、S024R−T033S−K235F−W241R、S024R−T033S−N243F、S024R−V104A、S024R−V104I−A232V、S024R−Y209A−N243F、S078R−K235F、S087D−S101G−S103A−V104I−A232V−S242R−Q245R、S099F−S105T−S106G−A194F−S212M、S101G−H249R、S101G−S103A−V104I、S101G−S103A−V104I−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R、S101G−S103A−V104I−G159D−A232V−Q245R−N248R、S101G−S103A−V104I−V150L−A232V−Q245R、S103A−A232V、S103A−A232V−H249R、S103A−A232V−Q245R、S103A−V104I−Q245R、S103N−H120F−Y167W−I198L−L233C、T022W−A194F−T213A−L233C−N238L、T022W−E089I−S216F、T033S−A048T、T033S−P086W−S156L−Y209A、T033S−P239T、T033S−T253A、T057R−N183D−Q236N、T143A−Y209A、V004E−T033S−S078R、V004R−S009A−T022R−S078R−S212F、Y209A−K235F、N043R−N076D−H249R、N018R−R045T、G020R−N076D−A230E−S242R、G020R−S024R−N043D−R045T、S024R−N043D−N076D−S242R−H249R、G020R−R045T−H249R、N043R−N076D−S153A−H249R、N043R−N076D−A230E−H249R、N018R−N043D−N076D−H249R、G020R−N043R−N076D−V227I、L111I−A215F−P239S、S024R−N116A−R186K−L233C−Q236N、G023A−S103N−S106G−S212M−A215F、Y209A−N243F、S024R−T033S−P129H−N184D−T253M、S024R−A085V−P086W−G118R−K235F、S024R−A272P、S024R−R269C、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N1
83D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−L217E−S242R−H249R、N076D−S087D−S101G−S103A−V104I−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−Q245R、及びS101G−S103A−V104I−V150L−A232V−S242R−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記変異体の合計正味電荷が、バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷と比較して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記合計正味電荷が:N43D、R45T、N62E、N76D、S101D、P129E、A158E、G159D、G159E、S166D、S188D、A230E、N18R、G20K、G20R、T22R、S24R、N43R、G118R、Q245R、H249R、N269R、E271F、及びE271Lから選択された1箇所以上の置換により得られ、前記プロテアーゼ変異体のアミノ酸位置が、配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の、対応するアミノ酸位置に割り振られた番号に従って番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020R−X−43R、X020K−X062E、X024F−X116L、X020K−X024F、X024R−X174T、X024R−X118R、X024R−X235F、X024R−X086R、X024R−X086W、X078R−X118R、X033S−X118R、X033S−X235F、X209A−X241R、X020R−X076D、X018R−X245R、X024R−X045T、X232V−X245R、X118R−X172V、X118R−X194T、X008T−X024R、X235F−X243F、X018R−X103A、X018R−X104I、X086W−X118R、X086W−X243F、X086W−X209A、X024C−X033S、X024R−X232V、X024R−X243F、X024R−X239Q、X024R−X101G、X024R−X141G、X024R−X033S、X024R−X274I、X024R−X209A、X078R−X086W、X101G−X232V、X033S−X148F、X033S−X086W、X033S−X201S、X033S−X078R、X033S−X241R、X033S−X209A、X230E−X249R、X232V−X249R、X118R−X235F、X076D−X245R、X086W−X235F、X024R−X247H、X024R−X104A、X078R−X235F、X101G−X249R、X103A−X232V、X033S−X048T、X033S−X239T、X033S−X253A、X143A−X209A、X209A−X235F、X018R−X045T、X209A−X243F、X024R−X272P、X024R−X269C、X101G−X104I、X104I−X232V、X076D−X249R、及びX024R−X076Dから選択されるアミノ酸置換の組み合わせを
含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020R−X076D、X024R−X045T、X230E−X249R、X018R−X045T、X018R−X245R、X101G−X232V、X024R−X232V、X232V−X245R、X024R−X101G、X018R−X104I、X018R−X103A、X101G−X249R、X232V−X249R、X103A−X232V、X076D−X245R、X101G−X104I、X104I−X232V、X076D−X249R、X024R−X076D、X024F−X116L、X020K−X024F、X020K−X062E、X033S−X118R、X024R−X086W、X024R−X118R、X024R−X086R、X209A−X241R、X024R−X241R、X024R−X235F、X118R−X209A、X078R−X118R、X033S−X235F、X024R−X174T、X086W−X209A、X008T−X024R、X086W−X118R、X033S−X241R、X024R−X243F、X024R−X209A、X033S−X086W、X024R−X033S、X086W−X243F、X033S−X201S、X024R−X239Q、X078R−X086W、X235F−X243F、X118R−X172V、X033S−X148F、X033S−X078R、X033S−X243F、X024C−X033S、X118R−X194T、X033S−X209A、X024R−X141G、X024R−X274I、X086W−X235F、X015T−X033S、X209A−X235F、X024R−X247H、X078R−X235F、X024R−X104A、X033S−X048T、X118R−X235F、X033S−X253A、X143A−X209A、X033S−X239T、X209A−X243F、X024R−X272P、及びX024R−X269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX004R−X009A−X020R−X242R、X020R−X043R−X241R、X020R−X242R−X269R、X004R−X009A−X020R−X043R、X004R−X020R−X249R、X018R−X024R−X244R、X009A−X022R−X212F−X241R、X020R−X043R−X269R、X018R−X024R−X242R、X004R−X009A−X043R−X241R、X020R−X043R−X244R、X020R−X022R−X242R、X004R−X020R−X043R、X004R−X009A−X020R−X043R−X242R、X020R−X043R−X242R、X020R−X043R−X242R−X249R、X020R−X212F−X249R、X004R−X009A−X241R、X001R−X009A−X043R、X020R−X043R−X249R、X009A−X020R−X043R−X241R、X020R−X022R−X043R、X020R−X249R−X269R、X020R−X022R−X241R、X004R−X009A−X024R−X043R−X241R、X009A−X043R−X078R、X004R−X020R−X024R−X244R、X020R−X022R−X078R−X242R、X020R−X024R−X242R−X249R、X004R−X009A−X078R−X241R、X009A−X043R−X078R−X242R、X004R−X020R−X024R、X009A−X043R−X212F、X020R−X043R−X212F、X024R−X078R−X212F、X009A−X020R−X024R−X043R、X009A−X022R−X043R−X078R、X020R−X022R−X212F−X241R、X020R−X043R−X212F−X241R、X009A−X043R−X241R、X020R−X043R−X271L、X020R−X022R−X078R−X241R、X020R−X024R−X043R−X242R、X020R−X022R−X043R−X241R、X009A−X020R−X043R−X212F、X004R−X009A−X020R−X024R−X242R、X020R−X043R−X249R−X271L、X020R−X022R−X024R−X242R、X009A−X022R−X078R−X212F、X020R−X043R−X242R−X271L、X009A−X022R−X078R−X212F−X241R、X004R−X020R−X024R−X249R、X020R−X022R−X271L、X020R−X022R−X043R−X212F、X004R−X020R−X024R−X043R−X242R、X004R−X020R−X024R−X043R、X004R−X009A−X022R−X078R−X212F、X020R−X022R−X078R−X212F−X241R、及びX020R−X022R−X269Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX018R−X020R−X043D−X045T−X230E、X018R−X043R−X045T−X242R−X249R、X024R−X043D−X249R、X018R−X020R−X045T、X020R−X024R−X076D−X249R、X024R−X043R−X230E−X242R、X018R−X024R−X043D−X230E、X020R−X076D、X018R−X024R−X043D−X076D−X249R、X024R−X043R−X076D−X249R、X018R−X024R−X045T−X242R、X020R−X043D−X076D−X230E−X249R、X020R−X043R−X045T−X242R、X018R−X024R−X076D−X249R、X018R−X020R−X024R−X043D−X045T−X233I−X242R、X024R−X043R−X230E、X018R−X020R−X043D、X043R−X242R−X249R、X020R−X043R−X045T−X230E、X043R−X076D−X242R−X249R、X020R−X024R−X045T−X230E−X242R、X024R−X045T−X076D−X230E−X242R−X249R、X024R−X045T、X024R−X043R−X045T−X076D−X230E−X249R、X018R−X024R−X043D−X045T−X249R、X018R−X043R−X045T−X249R、X024R−X043R−X242R、X018R−X020R−X043R−X076D−X249R、X020R−X024R−X043D−X249R、X020R−X043R−X230E−X242R、X020R−X043R−X242R、X018R−X043R−X076D−X230E、X020R−X024R−X043D−X242R、X020R−X043R−X230E、X018R−X020R−X043R−X076D−X242R−X249R、X043D−X045T−X076D−X249R、X018R−X043R−X242R−X249R、X018R−X020R−X043R−X045T−X242R、X018R−X020R−X043D−X230E−X242R、X020R−X024R−X043R−X045T−X249R、X024R−X043R−X249R、X020R−X024R−X27E−X043R−X076D−X230E、X024R−X043R−X045T−X242R、X018R−X020R−X024R−X043R−X045T−X076D−X230E、X020R−X043R−X076D−X230E−X249R、X018R−X043R−X045T−X242R、X020R−X242R−X249R、X018R−X043R−X076D−X230E−X242R−X249R、X018R−X024R−X076D、X020R−X024R−X27R−X043D−X242R−X249R、X018R−X020R−X024R−X043D−X076D−X242R、X018R−X043R−X076D−X242R−X249R、X018R−X024R−X043D−X230E−X249R、X018R−X020R−X043D−X249R、X018R−X020R−X043D−X045T−X076D−X242R、X024R−X043R−X076D−X230E−X242R、X020R−X024R−X38I−X043R−X045T−X076D−X242R−X249R、X018R−X020R−X043R、X018R−X024R−X045T−X230E−X242R、X018R−X020R−X249R、X024R−X043R−X076D、X018R−X020R−X024R−X043R−X045T−X076D−X249R、X018R−X043D−X045T−X076D−X242R−X249R、X024R−X043D−X242R−X249R、X018R−X020R−X024R−X043D−X045T−X242R、X020R−X024R−X043R−X076D、X018R−X020R−X043D−X045T−X230E−X242R、X020R−X024R−X043R−X045T−X076D−X242R−X249R、X018R−X043R−X045T−X076D−X242R、X018R−X020R−X043R−X076D−X230E−X242R、X018R−X024R−X043D−X249R、X018R−X024R−X043R−X045T−X230E−X249R、X018R−X020R−X043R−X045T−X076D−X249R、X018R−X024R−X242R、X018R−X043R−X045T−X076D−X230E−X242R、X045T−X242R−X249R、X018R−X024R−X043D−X242R、X018R−X020R−X043D−X045T−X240P、X024R−X043R−X045T−X242R−X249R、X018R−X024R−X30S−X31S−X32I−X33Q−X34V−X35F、X018R−X020R−X043R−X076D、X020R−X043D−X045T−X076D−X242R−X249R、X018R−X024R−X043D−X230E−X242R、X018R−X024R−X043D−X242R−X249R、X024R−X043D−X045T−X242R−X249R、X043R−X230E−X249R、X024R−X043R−X076D−X230E−X249R、X020R−X024R−X043D−X076D−X249R、X024R−X045T−X242R−X273V、X020R−X024R−X045T−X076D−X242R−X249R、X018R−X024R−X043D−X07
6D−X242R、X018R−X043R−X076D−X230E−X249R、X018R−X020R−X043R−X045T−X249R、X018R−X043R−X045T−X230E−X242R、X020R−X024R−X043D−X045T−X230E−X242R、X018R−X043D−X230E−X249R、X018R−X043R−X076D−X242R、X018R−X020R−X076D、X018R−X020R−X043D−X076D−X242R−X249R、X020R−X024R−X043D−X076D−X242R−X249R、X043D−X242R−X249R、X018R−X020R−X024R−X043R−X076D、X018R−X020R−X043D−X045T−X076D−X249R、X018R−X020R−X043R−X045T−X076D−X230E−X249R、X018R−X076D−X242R、X020R−X043R−X249R、X018R−X076D−X242R−X249R、X018R−X024R−X045T−X230E−X249R、X230E−X249R、X018R−X045T−X249R、X020R−X043R−X076D、X043R−X045T−X249R、X018R−X043D−X076D−X242R−X249R、X043R−X076D−X249R、X018R−X045T、X020R−X076D−X230E−X242R、X020R−X024R−X043D−X045T、X024R−X043D−X076D−X242R−X249R、X020R−X045T−X249R、X043R−X076D−X153A−X249R、X043R−X076D−X230E−X249R、X018R−X043D−X076D−X249R、及びX020R−X043R−X076D−X227Iから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101G−X103A−X104I−X232V−X236H−X245R−X252K、X101G−X103A−X104I−X232V−X245R−X248R、X101G−X103A−X104I−X159R−X232V−X245R−X248D、X101G−X103A−X104I−X159D−X232V−X245R−X248R、X101G−X103A−X104I−X232V−X245R、X101G−X103A−X104I−X159D−X232V−X245R、及びX101G−X103A−X104I−X232V−X245R−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X232V−X245R−X248D、X016S−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X158E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X159E−X188D−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X232V−X238R−X245R−
X248D、X022A−X101G−X103A−X104I−X129E−X159E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X158E−X159E−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X245R−X248D、X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X159E−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X128N−X129E−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128N−X158E−X159E−X188D−X232V−X245R−X248D、X022A−X024K−X101G−X103A−X104I−X128N−X158E−X159E−X232V−X245R−X248D、X101G−X103A−X104I−X129E−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X148I−X232V−X245R−X248D、X022A−X101G−X103A−X104I−X148I−X188D−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X128N−X129E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X128N−X129E−X158E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X148I−X158E−X188D−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X188D−X232V−X245R−X248D、X101G−X103A−X104I−X148I−X159E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D、及びX101G−X103A−X104I−X128N−X129E−X158E−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX022A−X024R−X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X245R−X248D−X249R、X022A−X024R−X101G−X103A−X104I−X158E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X159E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X148I−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D−X249R、X016S−X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129E−X159E−X232V−X238R−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X129E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X148I−X158E−X232V−X245R−X248D、X024R−X101G−X103A−X104I−X129E−X188D−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X158E−X159E−X188D−X232V−X238R−X245R−X248D、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X238R−X245R−X248D、X022A−X024R−X101G−X103A−X104I−X129E−X158E−X232V−X245R−X248D、X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X022A−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248D−X249R、及びX024R−X101G−X103A−X104I−X158E−X159E−X232V−X245R−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX104L−X128N−X158E−X186H−X249R、X128N−X158E−X188D−X249R、X062E−X128N−X158E−X159E−X271F、X062E−X158E−X188D−X249R−X271F、X062E−X158E−X186H−X249R−X271F、X128N−X158E−X188D−X209E−X271F、X062E−X159E−X188D−X249R、X016S−X062E−X158E−X186H−X249R、X062E−X158E−X159E−X249R、X101A−X128N−X158E−X209E−X249R、X128N−X158E−X186H−X271F、X062E−X158E−X188D−X249R、X062E−X158E−X186H−X271F、X062E−X158E−X186H−X249R、X062E−X101A−X186H−X249R、X062E−X101A−X158E−X186H−X271F、X062E−X104L−X158E−X188D−X249R−X271F、X062E−X159E−X186H−X249R、X062E−X159E−X249R、X128N−X158E−X186H−X249R、X128N−X158E−X188D−X271F、X062E−X158E−X249R、X062E−X186H−X188D−X249R−X271F、X12
8N−X158E−X209E−、X062E−X101A−X158E−X249R、X104L−X128N−X158E−X186H−X271F、X062E−X101A−X158E−X186H−X249R−X271F、X016S−X062E−X158E−X249R、X062E−X101A−X159E−X249R、X128N−X158E−X186H−X188D−X271F、X101A−X128N−X158E−X186H−X271F、X062E−X101A−X188D−X249R、X101A−X104L−X158E−X186H−X188D−X249R、X062E−X159E−X249R−X271F、X128N−X158E−X159E−X271F、X016S−X062E−X104L−X158E−X186H−X271F、X022A−X128N−X158E−X249R、X128N−X158E−X249R、X062E−X101A−X104L−X158E−X186H−X271F、X016S−X062E−X158E−X186H−X271F、X104L−X128N−X158E−X249R、X104L−X128N−X158E−X188D−X249R、X022A−X062E−X158E、X062E−X101A−X188D−X249R−X271F、X062E−X158E−X249R−X271F、X104L−X128N−X158E−X186H−X188D−X271F、X062E−X101A−X186H−X271F、X062E−X104L−X159E−X249R、X062E−X186H−X249R、X062E−X101A−X186H−X249R−X271F、X101A−X158E−X186H−X188D−X249R、X062E−X101A−X186H、X101A−X128N−X129E−X186H−X249R、X101A−X103G−X158E−X186H−X249R、X016S−X062E−X104L−X186H−X188D−X271F、X104L−X158E−X186H−X249R、X101A−X128N−X158E−X188D−X209E−X271F、X062E−X101A−X186H−X188D−X271F、X016S−X062E−X158E−X249R−X271F、X062E−X128N−X158E、X062E−X128N−X159E−X249R、X062E−X101A−X158E−X188D−X249R、X101A−X128N−X158E−X249R、X062E−X158E−X186H−X188D−X249R、X016S−X104L−X158E−X186H−X271F、X062E−X148I−X159E、X062E−X101A−X158E−X186H−X249R、X062E−X101A−X186H−X188D−X249R、X104L−X158E−X186H−X188D−X249R、X062E−X101A−X104L−X186H−X188D−X271F、X022A−X101A−X158E−X186H−X249R、X101A−X128N−X158E−X209E、X158E−X186H−X188D−X249R−X271F、X104L−X158E−X186H−X188D−X249R−X271F、X101A−X104L−X158E−X186H−X249R、X104L−X158E−X249R、X101A−X104L−X128N−X158E−X186H−X271F、X016S−X104L−X188D−X249R、X101A−X104L−X158E−X186H−X188D−X271F、X104L−X128N−X159E−X271F、X104L−X158E−X186H−X249R−X271F、X158E−X186H−X249R、X101A−X158E−X186H−X249R、X104L−X158E−X188D−X249R−X271F、X016S−X128N−X158E−X186H、X104L−X128N−X186H−X188D−X249R、X016S−X101A−X128N−X186H、X016S−X062E−X128N−X186H−X271F、X016S−X128N−X186H−X271F、X128N−X129E−X186H、X158E−X186H−X249R−X271F、X016S−X158E−X249R、X016S−X158E−X186H−X249R、X016S−X022A−X158E−X186H−X271F、X089P−X101A−X129E−X186H、X022A−X128N−X158E−X186H、X101A−X104L−X128N−X158E−X186H、X022A−X128N−X186H−X188D−、X062E−X104L−X158E−X186H−X188D−X249R、X022A−X158E−X186H−X249R−X271F、X022A−X104L−X158E−X249R、X101A−X111V−X129E、X016S−X158E−X249R−X271F、X016S−X111V−X188D−、X022A−X104L−X186H−X188D−X249R、及びX104L−X148I−X188D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX001R−X101G−X103A−X104I−X232V−X245R、X004R−X101G−X103A−X104I−X232V−X245R、X043R−X101G−X103A−X104I−X232V−X245R−X271L、X078R−X101G−X103A−X104I−X232V−X245R、X004R−X043R−X101G−X103A−X104I−X232V−X245R、X018R−X043R−X101G−X103A−X104I−X232V−X245R、X020R−X101G−X103A−X104I−X232V−X245R、X101G−X103A−X104I−X232V−X245R−X271L、X020R−X043R−X101G−X103A−X104I−X232V−X245R、X024R−X043R−X101G−X103A−X104I−X232V−X245R、X020R−X025R−X116A−X167W、X018R−X101G−X103A−X104I−X232V−X245R、X022R−X101G−X103A−X104I−X232V−X245R、X078R−X103N−X106G−X167W−X236N、X018R−X043D−X101G−X103A−X104I−X232V−X245R−X269R、X043R−X101G−X103A−X104I−X232V−X245R−X269R、X024R−X101A−X120F−X194F−X249R、X020R−X043D−X101G−X103A−X104I−X232V−X245R−X269R、X101G−X103A−X104I−X212F−X232V−X245R、X020R−X144R−X185I−X233C−X236N、X023A−X078R−X216F−X236N−X249R、X101G−X103A−X104I−X232V−X245R−X269R、X101G−X103A−X104I−X115R−X232V−X245R、X052N−X078R−X103N−X148I−X213A、X018R−X043D−X101G−X103A−X104I−X232V−X245R−X249R、X024R−X043D−X101G−X103A−X104I−X232V−X245R−X249R、X024R−X043D−X101G−X103A−X104I−X232V−X245R−X269R、X025R−X089I−X116A−X239S−X270C、X024R−X101G−X103A−X104I−X232V−X245R、X148I−X213A−X252R、X024R−X025R−X183D−X192W−X239S、X046R−X194F−X212M、X104L−X217E−X224A−X249R−X252R、X023A−X091F−X121F−X192W−X236N、X101G−X103A−X104I−X232V−X244R−X245R、X099F−X144R−X167W−X252R、X101G−X103A−X104I−X232V−X245R−X249R、X043R−X101G−X103A−X104I−X232V−X245R、X022W−X078R−X167W−X212M−X270C、X121F−X252R−X270C、X020R−X103N−X216F−X236N−X252R、X043R−X101G−X103A−X104I−X232V−X245R−X249R、X023A−X052N−X192W−X198L−X252R、X025R−X046R−X121F、X024R−X078R−X104L−X116A−X183D、X046R−X059A−X103N−X211Q−X212M、X020R−X052N−X062Q−X091F−X192W、X023A−X052N−X144R−X192W−X216F、X101G−X103A−X104I−X232V−X242R−X245R、X052N−X103N−X116A−X148I−X192W、X089I−X116A−X117F−X224A−X249R、X144R−X211Q−X238L−X239S−X249R、X043A−X062Q−X194F−X211Q、X020R−X024R−X052N−X059A−X216F、X024R−X167W−X224A−X249R、X057R−X167W−X249R、X025R−X103N−X186K−X194F−X224A、X105T−X128N−X144R−X148I−X212M、X020R−X059A−X144R−X192W−X224A、X024R−X043A−X117F−X194F−X211Q、X117F−X194F−X213A−X270C、X078R−X091F−X121F−X233C−X252R、X057R−X099F−X105T−X198L−X213A、X023A−X091F−X101A−X198L−X252R、X062Q−X103N−X121F−X144R−X249R、X043R−X101G−X103A−X104I−X232V−X242R−X245R、X023A−X024R−X117F−X212M−X216F、X104L−X213A−X216F、X194F−X211Q−X236N、X062Q−X103N−X117F−X194F、X024R−X062Q−X104L−X106G−X249R、X057R−X089I−X198L、X046R−X059A−X106G−X217E−X249R、X117F−X213A−X215F、X101A−X120F−X192W−X215F−X224A、X043A−X057R−X117F−X144R−X183D、X046R−X183D−X238L、X025R−X043A−X089I−X117F、X078R−X104L−X213A−X215F−X224A、X091F−X099F−X101A−X105T−X167W、X106G−X117F−X238L、X046R−X089I−X091F−X101A−X116A、X020R−X062Q−X089I−X186K−X212M、X057R−X099F−X121F−X185I−X192W、X046R−X089I−X192W−X233C−X270C、X089I−X117F−X185I−X215F−X233C、X052N−X104L−X183D−X216F−X249R、X078R−X09
9F−X116A−X186K−X224A、X025R−X105T−X128N−X144R−X270C、X105T−X211Q−X216F、X024R−X046R−X091F−X121F、X106G−X185I−X216F−X236N、X062Q−X101A−X236N−X252R−X270C、X025R−X043A−X091F−X198L−X270C、X020R−X023A−X104L−X192W−X233C、X024R−X043A−X105T−X106G−X198L、X020R−X089I−X217E、X024R−X091F−X198L−X215F−X239S、X046R−X089I−X099F−X186K−X212M、X104L−X120F−X186K−X216F−X252R、X022W−X194F−X213A−X233C−X238L、X099F−X105T−X106G−X194F−X212M、X089I−X105T−X116A−X215F−X216F、X025R−X116A−X120F−X224A−X270C、X043A−X059A−X101A−X216F−X224A、X057R−X183D−X236N、X025R−X062Q−X128N−X144R−X185I、X103N−X120F−X167W−X198L−X233C、X022W−X089I−X216F、X024R−X106G−X116A−X212M−X224A、X020R−X052N−X101A−X198L−X233C、X089I−X091F−X185I−X211Q−X270C、X111I−X215F−X239S、X024R−X116A−X186K−X233C−X236N、及びX023A−X103N−X106G−X212M−X215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020R−X022W−X078R−X101A−X103A−X104I−X116S−X213A−X215F−X232V−X245R、X018R−X078R−X101G−X103A−X104I−X232V−X245R、X024R−X045T−X101G−X103A−X104I−X232V−X245R−X269R、X020R−X022W−X078R−X101G−X103A−X104I−X116A−X232V−X245R、X020R−X22W−X101G−X103A−X104I−X232V−X245R、X018R−X043R−X101G−X103A−X104I−X232V−X245R、X018R−X022W−X024R−X076D−X101A−X116A−X232V−X245R、X018R−X104I−X232V−X249R、X018R−X024R−X076D−X101A−X116A−X211Q−X249R、X018R−X043D−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X018R−X043R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X045T−X076D−X101G−X103A−X104I−X232V−X245R−X269R、X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X020R−X043D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X043D−X076D−X101G−X103A−X104I−X232V−X245R−X269R、X024R−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X103A−X232V−X249R、X018R−X101G−X104I−X232V−X245R、X020R−X024R−X101G−X103A−X104I−X217E−X232V−X245R−X249R、X018R−X22K−X043D−X101G−X103A−X104I−X232V−X245R、X043R−X045T−X101G−X103A−X104I−X232V−X245R−X269R、X020R−X22W−X101G−X103A−X104I−X211Q−X232V−X245R、X024R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X020R−X22W−X078R−X101A−X103A−X104I−X116A−X183D−X232V、X018R−X024R−X076D−X116A−X215F−X249R、X018R−X043R−X045T−X101G−X103A−X104I−X232V−X245R、X024R−X043R−X076D−X101G−X103A−X104I−X232V−X245R、X020R−X022W−X101G−X103A−X104I−X232V−X245R、X020R−X022W−X101G−X103A−X104I−X211Q−X232V−X245R、X020R−X022W−X078R−X101G−X103A−X104I−X116A−X213A−X215F−X232V−X245R、X043D−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X024R−X076D−X101A−X116A−X213A−X249R、X018R−X024R−X076D−X116A−X211Q−X249R、X043R−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X101G−X245R、X020R−X22W−X101A−X103A−X104I−X211Q−X213A−X232V−X245R、X020R−X024R−X043D−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X020R−X078R−X101G−X103A−X104I−X211Q−X213A−X215F−X232V−X245R、X045T−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X024R−X043D−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X101G−X103A−X249R、X018R−X22W−X024R−X076D−X101A−X116A−X232V−X245R、X018R−X101G−X104I−X232V−X249R、X020R−X22W−X101A−X103A−X104I−X215F−X232V−X245R、X018R−X024R−X076D−X211Q−X213A−X249R、X018R−X022W−X024R−X076D−X101A−X198L−X249R、X024R−X101G−X103A−X104I−X232V−X245R、X020R−X076D−X101G−X103A−X104I−X232V−X245R−X269R、X020R−X101G−X103A−X104I−X232V−X245R−X269R、X043D−X078R−X101G−X103A−X104I−X232V−X245R、X020R−X101G−X104I−X213A−X215F−X232V−X245R、X020R−X101G−X103A−X104I−X116A−X215F−X232V−X245R、X024R−X103A−X104I−X249R、X018R−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X024R−X101G−X104I−X245R、X020R−X101G−X103A−X104I−X211Q−X213A−X215F−X232V−X245R、X024R−X103A−X104I−X232V−X249R、X018R−X024R−X076D−X116A−X211Q−X215F−X249R、X018R−X245R、X024R−X103A−X245R、X024R−X103A−X104I−X245R、X020R−X078R−X101G−X232V−X245R、X018R−X024R−X076D−X104I−X249R、X018R−X024R−X104I−X249R、X024R−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X076D−X211Q−X215F−X249R、X019H−X020R−X022W−X078R−X101G−X103A−X104I−X211Q−X232V−X245R、X018R−X024R−X076D−X101A−X198L−X211Q−X213A−X249R、X018R−X024R−X043D−X101G−X103A−X104I−X232V−X245R、X020R−X22W−X103A−X104I−X232V−X245R、X018R−X103A−X104I−X249R、X018R−X022W−X024R−X076D−X101A−X198L−X215F−X249R、X018R−X024R−X101G−X104I−X232V、X078R−X101G−X103A−X104I−X232V−X245R−X269R、X024R−X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X020R−X043D−X076D−X101G−X103A−X104I−X232V−X245R、X018R−X22W−X024R−X076D−X116A−X213A−X249R、X018R−X024R−X101G−X104I、X020R−X101A−X103A−X104I−X215F−X232V−X245R、X018R−X045T−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X101G−X103A−X245R、X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X020R−X022W−X101A−X103A−X104I−X211Q−X215F−X232V−X245R、X020R−X22W−X078R−X101G−X103A−X104I−X116A−X213A−X215F−X232V−X245R、X020R−X078R−X101G−X103A−X104I−X215F−X232V−X245R、X020R−X022W−X078R−X101G−X103A−X104I−X116A−X183D−X232V−X245R、X076D−X101G−X103A−X104I−X232V−X245R、X076D−X101G−X103A−X104I−X232V−X245R−X269R、X020R−X22W−X101A−X103A−X104I−X232V−X245R、X020R−X101G−X103A−X232V−X245R、X020R−X022W−X078R−X101A−X103A−X104I−X116A−X183D−X232V−X245R、X018R−X020R−X024R−X045T−X076D−X101G−X103A−X104I−X232V−X245R−X269R、X043R−X045T−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X101G−X104I−X249R、X020R−X22W−X078R−X101G−X103A−X104I−
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5F−X249R−X269H、X018R−X043D−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X045T−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X078R−X101G−X103A−X104I−X217E−X232V−X245R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X198L−X213A−X215F−X249R、X018R−X020R−X024R−X076D−X183D−X198L−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X211Q−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X198L−X211Q−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X249R、X020R−X022W−X101G−X103A−X104I−X116A−X183D−X198L−X211Q−X213A−X215F−X232V−X245R、X104I−X232V、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X183D−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X211Q−X213A−X249R、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X249R、X043D−X045T−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X211Q−X249R、X018R−X020R−X043R−X101G−X103A−X104I−X217E−X232V−X245R、X024R−X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X043R−X045T−X076D−X078R−X101G−X103A−X104I−X166F−X176P−X179V−X184T−X187P−X194P、X018R−X022W−X024R−X041E−X076D−X101A−X160T−X183D−X211Q−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X213A−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X198L−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X183D−X211Q−X215F−X249R、X024R−X076D−X104I、X018R−X076D−X101G−X232V、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X215F−X249R、X018R−X024R−X031F−X076D−X116A−X183D−X211Q−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X213A−X249R−X269S、X018R−X020R−X024R−X076D−X101A−X116A−X198L−X215F−X249R、X018R−X043R−X076D−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X114T−X198L−X211Q−X215F−X249R、X024R−X043R−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X024R−X076D−X103A−X104I−X232V、X018R−X020R−X022W−X024R−X076D−X101A−X198L−X211Q−X215F−X249R、X101G−X104I−X232V、X018R−X022W−X024R−X076D−X183D−X198L−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X183D−X213A−X249R、X018R−X024R−X076D−X101A−X183D−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X211Q−X213A−X249R、X018R−X078R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X211Q−X215F−X249R−X260A、X076D−X249R、X018R−X022W−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X116A−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X213A−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X183D−X198L−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X183D−X249R、X076D−X104I−X249R、X020R−X022W−X101A−X103A−X104I−X116A−X183D−X211Q−X213A−X215F−X232V−X245R、X024R−X043R−X045T−X078R−X101G−X103A−X104I−X217E−X232V−X245R、X018R−X020R−X022W−X024R−X076D−X183D−X198L−X215F−X249R、X018R−X076D−X101G−X103A、X020R−X024R−X101G−X103A−X104I−X232V−X245R−X269R、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R、X101G−X103A−X232V、X024R−X076D−X101G−X232V、X018R−X022W−X024R−X076D−X101A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X211Q−X215F−X249R、X018R−X020R−X024R−X076D−X183D−X198L−X249R、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X249R、X018R−X020R−X024R−X076D−X116A−X156V−X183D−X211Q−X215F−X249R−X269S、X045T−X076D−X101G−X103A−X104I−X232V−X245R−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X198L−X249R、X018R−X020R−X022W−X024R−X076D−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X211Q−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X116A−X249R、X018R−X076D−X101G、X018R−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X018R−X020R−X022W−X024R−X076D−X101A−X116A−X198L−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X249R、X018R−X076D−X232V、X018R−X020R−X024R−X076D−X101A−X232V−X245R、X018R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X018R−X022W−X024R−X076D−X183D−X213A−X215F−X249R、X018R−X024R−X076D−X101A−X116A−X211Q−X213A−X237D−X249R、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X211Q−X249R−X275S、X018R−X022W−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X215F−X249R、X024R−X076D、X018R−X024R−X076D−X183D−X211Q−X215F−X249R、X018R−X022W−X024R−X076D−X116A−X183D−X198L−X213A−X215F−X249R、X076D−X104I−X232V−X249R、X018R−X076D−X103A−X232V、X018R−X020R−X024R−X076D−X101A−X116A−X183D−X198L−X211Q−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X183D−X213A−X249R、X018R−X020R−X024R−X076D−X101A−X175E−X183D−X211Q−X215F−X249R、X018R−X020R−X043D−X078R−X101G−X103A−X104I−X217E−X232V−X245R−X273E、X020R−X024R−X043D−X045T−X076D−X101G−X103A−X104I−X232V−X245R、X005S−X101G−X103A−X104I−X232V−X245R−X249R、X103A−X104I−X232V、X018R−X020R−X024R−X068A−X076D−X101A−X116A−X213A−X215F−X249R、X018R−X022W−X024R−X076D−X101A−X198L−X215F−X249R−X275S、X018R−X024R−X076D−X183D−X198L−X211Q−X213A−X249R、及びX043D−X045T−X101G−X103A−X104I−X232V−X245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる
、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX018R−X024R−X043R−X076D−X249R−X269R、X018R−X022R−X024R−X043R−X076D−X249R、X018R−X043D−X101G−X103A−X104I−X232V−X245R、X020R−X043D−X101G−X103A−X104I−X232V−X245R、X043D−X101G−X103A−X104I−X232V−X245R−X269R、X043D−X078R−X101G−X103A−X104I−X232V−X245R、X043R−X076D−X101G−X103A−X104I−X232V−X245R、X022R−X043R−X101G−X103A−X104I−X232V−X245R、X043R−X078R−X101G−X103A−X104I−X232V−X245R、X020R−X076D−X101G−X103A−X104I−X232V−X245R、X043R−X076D−X101G−X103A−X104I−X232V−X245R、X022R−X076D−X101G−X103A−X104I−X232V−X245R、X076D−X078R−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X043R−X076D−X249R、X018R−X024R−X076D−X242R−X249R、X018R−X024R−X076D−X249R−X269R、X018R−X022R−X024R−X076D−X249R、X018R−X024R−X076D−X078R−X249R、X018R−X024R−X043D−X076D−X249R−X269R、X018R−X022R−X024R−X043D−X076D−X249R、X018R−X024R−X043D−X076D−X078R−X249R、X020R−X101G−X103G−X104I−X232V−X245R、X020R−X101G−X103A−X104L−X232V−X245R、X020R−X101G−X103A−X104V−X232V−X245R、X020R−X101G−X103S−X104I−X232V−X245R、X020R−X101G−X103S−X104L−X232V−X245R、X020R−X101S−X103S−X104I−X232V−X245R、X020R−X101S−X103S−X104L−X232V−X245R、X020R−X101A−X103A−X104L−X232V−X245R、X020R−X101S−X103S−X104V−X232V−X245R、X020R−X101S−X103A−X104I−X232V−X245R、X020R−X101S−X103A−X104V−X232V−X245R、X020R−X101S−X103G−X104I−X232V−X245R、X020R−X101S−X103G−X104V−X232V−X245R、X020R−X101A−X103A−X104V−X232V−X245R、X020R−X101A−X103S−X104I−X232V−X245R、X020R−X101A−X103S−X104V−X232V−X245R、X018R−X024R−X043R−X076D−X078R−X249R、X024R−X043D−X101G−X103A−X104I−X232V−X245R、X043D−X101G−X103A−X104I−X232V−X245R−X249R、X024R−X076D−X101G−X103A−X104I−X232V−X245R、X076D−X101G−X103A−X104I−X232V−X242R−X245R、X018R−X020R−X024R−X076D−X217E−X249R、X018R−X024R−X043R−X076D−X217E−X249R、X018R−X024R−X043D−X076D−X242R−X249R、X018R−X020R−X024R−X043R−X076D−X249R、X020R−X101A−X103G−X104V−X232V−X245R、X043D−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X076D−X217E−X249R−X269R、及びX018R−X024R−X076D−X217E−X242R−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020R−X101A−X103A−X104I−X118R−X232V−X245R、X020R−X024R−X116A−X213A、X043R−X101A−X116A−X215F−X269R、X024R−X043R−X101A−X116A、X024R−X043R−X101A−X116A−X215F−X269R、X020R−X101G−X103A−X104I−X215F−X232V−X245R、X043R−X101A−X269R、X024R−X043R−X116A−X213A−X269R、X020R−X024R−X043R−X045T−X101A−X213A、X024R−X043R−X116A−X215F−X269R、X020R−X024R−X213A−X215F、X020R−X116A−X269R、X024R−X116A−X213A−X269R、X043R−X101A−X116A−X269R、X101G−X103A−X104I−X116A−X213A−X232V−X245R−X269R、X024R−X043R−X045T−X101A−X116A−X215F−X269R、X020R−X043R−X101A−X269R、X101A−X103A−X104I−X213A−X232V−X245R−X269R、X024R−X215F−X269R、X043R−X101A−X116A−X213A−X215F−X269R、X043R−X101A−X213A−X269R、X020R−X024R−X043R−X045T−X116A−X213A、X101G−X103A−X104I−X232V−X245R−X269R、X024R−X043R−X045T−X101A−X116A−X213A−X269R、X024R−X043R−X045T−X269R、X020R−X043R−X045T−X101A−X269R、X024R−X043R−X116A−X269R、X020R−X024R−X043R−X045T、X043R−X116A−X269R、X024R−X043R−X101A−X215F−X269R、X024R−X043R−X045T−X213A−X215F−X269R、X020R−X024R−X045T−X269R、X020R−X043R−X101A−X116A−X213A−X215F、X020R−X101G−X103A−X104I−X213A−X215F−X232V−X245R、X020R−X024R−X045T−X116A−X269R、X020R−X101A−X116A−X269R、X024R−X043R−X215F、X020R−X024R−X213A、X024R−X043R−X101A−X215F、X020R−X024R−X043R−X045T−X116A、X020R−X024R−X043R−X045T−X101A−X269R、X020R−X024R−X101A−X215F、X020R−X024R−X116A−X213A−X215F、X020R−X024R−X116A、X020R−X024R−X101A−X116A、X043R−X213A−X215F−X269R、X024R−X101A−X269R、X024R−X043R−X116A−X215F、X020R−X038A−X043R−X101A、X020R−X024R−X116A−X215F、X024R−X043R−X101A−X213A、X014L−X020R−X024R−X043R−X045T−X101A−X215F、X020R−X024R−X215F、X020R−X116A−X215F−X269R、X020R−X045T−X116A−X269R、X020R−X024R−X043R−X045T−X215F、及びX020R−X024R−X043R−X045T−X116A−X213A−X215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX043R−X076D−X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X024R−X043R−X076D−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R−X271F−X271F、X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R−X271F、X076D−X101G−X103A−X104I−X114V−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X024R−X076D−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X024R−X043R−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X043R−X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101A−X103A−X104I−X158E−X166D−X188D−X217E−X232V−X245R−X248D−X249R、X076D−X101G−X103A−X104I−X128L−X158E−X188D−X232V−X245R−X248D−X249R−X271F、及びX043R−X076D−X101G−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンス(B. amyloliquefaciens)のサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX022A−X101G−X103A−X104I−X159D−X217E−X232V−X245R−X248D−X271F、X022A−X043R−X101G−X103A−X104I−X159D−X188D−X217E−X232V−X245R−X248D−X271F、X022A−X101G−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X271F、X043R−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X04
3R−X076D−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R−X271F、X024R−X101G−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X022A−X076D−X101G−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X271F、X022A−X043R−X076D−X101G−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X271F、X022A−X076D−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X022A−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X076D−X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X043R−X101A−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R、X024R−X076D−X101A−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271F、X076D−X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101A−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271F、X043R−X076D−X101A−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271F、X101G−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271F、X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R−X271F、X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X076D−X101A−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271F、X101G−X103A−X104I−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X158E−X188D−X232V−X245R−X248D−X249R、X076D−X101G−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R−X271F、X043R−X076D−X101A−X103A−X104I−X158E−X166D−X188D−X232V−X245R−X248D−X249R、及びX076D−X101A−X103A−X104I−X158E−X188D−X217E−X232V−X245R−X248D−X249R−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX017R−X022A−X076D−X101G−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X271F、X022A−X043R−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X022A−X101G−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X249R−X271F、X017R−X022A−X076D−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X022A−X076D−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X249R−X271F、X022A−X101G−X102A−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X271F、及びX022A−X043R−X076D−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X249R−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101S−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101S−X103G−X104V−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103S−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101A−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101A−X103A−X104L−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103G−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101S−X103G−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101S−X103S−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101S−X103S−X104V−X158E−X188D−X232V−X245R−X248D−X249R、X101A−X103S−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101A−X103S−X104I−X159E−X232V−X245R−X248D−X249R、X101S−X103A−X104I−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104L−X158E−X188D−X232V−X245R−X248D−X249R、X101A−X103A−X104L−X159E−X232V−X245R−X248D−X249R、X101A−X103S−X104L−X159E−X232V−X245R−X248D−X249R、X101G−X103S−X104L−X159E−X232V−X245R−X248D−X249R、X101S−X103A−X104L−X159E−X232V−X245R−X248D−X249R、X101A−X103G−X104V−X159E−X232V−X245R−X248D−X249R、及びX101S−X103A−X104V−X159E−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX026F−X051W−X104L−X106E、X026F−X031F−X078N−X102A−X160D、X020K−X100S−X116L−X158E−X166D−X243F、X033S−X043W−X218D−X239G−X243F、X022L−X038F−X048R−X062E−X100S−X186K、X101D−X103N−X116L−X144R−X215D、X104L−X105T−X213A−X217E−X256N、X043W−X101D−X212M−X243F、X026F−X048R−X105T−X213A−X218D−X224A、X024F−X101D−X118R−X215D−X250I−X272F、X121F−X185E−X224A−X239G、X022L−X031F−X102A−X128D−X224A−X243F、X062E−X078N−X102A−X116L−X144R−X250I、X022L−X038F−X121F−X160D−X272F、X026F−X078N−X159C−X186K−X243F、X024F−X048R−X118R−X166D−X217E、X023A−X038F−X078N−X100S−X212M−X215D、X100S−X116L−X158E−X213A、X078N−X104L−X118R−X128D、X102A−X103N−X105T−X194E、X022L−X078N−X128D−X213A、X027R−X100S−X118R−X160D−X188D−X243F、X024F−X102A−X186K−X213A−X217E−X243F、X033S−X105T−X188D−X216F、X023A−X100S−X194E−X212M、X048R−X128D−X185E−X239G、X020K−X024F−X033S−X129E−X194E、X020K−X027R−X129E−X166D−X239G、X022L−X023A−X027R−X101D−X104L−X216F、X033S−X118R−X129E−X194E−X239G、X022L−X078N−X116L−X129E−X256N、X027R−X101D−X103N−X105T−X272F、X048R−X078N−X116L−X185E−X217E−X239G、X023A−X024F−X027R−X062E、X024F−X103N−X104L−X118R−X188D、X026F−X104L−X256N−X272F、X024F−X043W−X104L−X121F−X129E、X062E−X078N−X116L−X224A、X023A−X024F−X051W−X158E、X027R−X038F−X102A−X116L、X062E−X078N−X144R−X212M、X031F−X116L−X256N−X272F、X022L−X033S−X104L−X116L−X160D−X186K、X024F−X118R−X129E−X186K−X213A、X043W−X105T−X213A−X215D−X216F、X031F−X105T−X186K−X188D、X026F−X194E−X213A−X256N、及びX103N−X160D−X250I−X256Nから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX022A−X024R−X101D−X103A−
X104I−X118R−X159D−X188D−X232V−X248D−X271F、X022A−X024R−X103A−X104I−X129E−X159D−X188D−X232V−X248D−X271F、X022A−X024R−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X248D、X022A−X024R−X101D−X103A−X104I−X118R−X129E−X159D−X188D−X232V−X245R−X248D、X022A−X024R−X101D−X103A−X104I−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X103A−X104I−X118R−X129E−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D、X022A−X043R−X101D−X103A−X104I−X118R−X129E−X159D−X188D−X232V−X248D−X271F、X022A−X024R−X043R−X101D−X103A−X104I−X159D−X188D−X232V−X245R−X248D、X022A−X103A−X104I−X159D−X188D−X232V−X248D、X022A−X024R−X103A−X104I−X118R−X129E−X159D−X188D−X232V−X248D−X271F、X022A−X024R−X103A−X104I−X159D−X188D−X217D−X232V−X245R−X248D−X271F、X022A−X043R−X062E−X103A−X104I−X159D−X188D−X232V−X245R−X248D−X271F、X022A−X043R−X103A−X104I−X129E−X159D−X188D−X232V−X245R−X248D、X022A−X024R−X103A−X104I−X159D−X188D−X217D−X232V−X248D−X271F、X022A−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X245R−X248D、X022A−X024R−X101D−X103A−X104I−X118R−X128I−X159D−X188D−X232V−X245R−X248D、X022A−X024R−X043R−X103A−X104I−X159D−X188D−X217D−X232V−X248D−X271F、X022A−X043R−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X248D−X271F、X022A−X043R−X103A−X104I−X118R−X159D−X188D−X232V−X248D−X271F、X022A−X103A−X104I−X128I−X129E−X159D−X188D−X232V−X248D−X271F、X022A−X103A−X104I−X159D−X188D−X217D−X232V−X245R−X248D−X271F、X022A−X043R−X103A−X104I−X128I−X159D−X188D−X232V−X245R−X248D、X022A−X101D−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X245R−X248D−X271F、X022A−X103A−X104I−X118R−X129E−X159D−X188D−X232V−X245R−X248D−X271F、X022A−X024R−X043R−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X248D、X022A−X062E−X103A−X104I−X118R−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X101D−X103A−X104I−X118R−X129E−X159D−X188D−X217D−X232V、X022A−X024R−X103A−X104I−X159D−X188D−X217D−X232V−X248D、X022A−X024R−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X217D−X232V−X248D−X271F、及びX022A−X103A−X104I−X118R−X159D−X188D−X217D−X232V−X245R−X248D−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020K−X024F−X062E−X188D−X239G、X024F−X062E−X116L−X239G、X020K−X023A−X062E−X188D、X020K−X023A−X024F−X062E−X118R−X188D−X213A、X020K−X043W−X062E−X116L−X188D−X213A−X239G、X023A−X062E−X116L−X118R、X023A−X024F−X062E−X116L−X118R、X024F−X116L、X024F−X062E−X188D−X213A、X023A−X062E−X116L−X118R−X188D−X239G、X020K−X024F−X062E、X020K−X043W−X062E−X116L−X239G、X024F−X062E−X116L−X213A−X239G、X020K−X024F−X043W−X062E−X116L−X213A、X020K−X023A−X024F−X062E−X116L−X188D−X213A、X024F−X062E−X188D−X239G、X023A−X043W−X062E−X116L−X118R−X213A、X062E−X188D−X239G、X020K−X024F−X062E−X239G、X024F−X116L−X118R−X188D−X239G、X020K−X023A−X062E−X116L−X118R−X213A、X020K−X023A−X024F−X062E−X188D−X213A−X239G、X024F−X043W−X118R−X188D、X023A−X024F−X116L−X118R−X188D−X213A、X020K−X023A−X043W−X116L−X188D−X213A−X239G、X023A−X024F−X116L−X188D−X239G、X023A−X043W−X116L−X118R−X188D、X023A−X024F−X118R−X188D−X239G、X023A−X024F−X043W−X062E−X116L−X118R、X020K−X043W−X188D−X213A、X024F−X062E−X118R−X239G、X023A−X043W−X188D−X213A、X020K−X024F−X043W−X062E−X116L−X118R−X188D−X239G、X020K−X116L−X188D−X239G、X020K−X043W−X062E−X118R、X020K−X043W−X116L−X188D−X213A、X020K−X024F、X023A−X043W−X116L−X239G、X023A−X024F−X043W−X116L−X118R−X188D−X239G、X020K−X023A−X043W−X213A、及びX023A−X024F−X062E−X118R−X213A−X239Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020K−X023A−X043W−X118R−X128I−X129E−X159D−X188D、X024F−X118R−X128I−X129E−X159D、X020K−X024F−X062E−X116L−X118R−X188D、X020K−X062E−X116L−X188D、X062E−X116L−X118R−X213A、X020K−X023A−X062E−X116L−X188D、X062E−X116L−X118R−X188D、X020K−X062E−X116L−X213A、X020K−X023A−X062E−X116L、X020K−X062E−X188D−X213A、X020K−X062E、X020K−X024F−X062E−X116L−X188D、X020K−X043W−X062E−X116L−X188D、X020K−X024F−X062E−X188D−X213A、X062E−X116L−X188D−X213A、X020K−X062E−X116L、X020K−X023A−X062E−X116L−X188D−X213A、X023A−X024F−X062E−X116L−X213A、X022A−X043R−X103A−X104I−X128I−X129E−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D−X271F、X024F−X062E−X116L−X188D、X022A−X024R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D、X023A−X062E−X116L−X188D、X043W−X062E−X116L、X020K−X023A−X116L−X188D、X043W−X062E−X116L−X188D、X024F−X062E−X116L、X062E−X116L−X188D、及びX022A−X024R−X103A−X104I−X128I−X159D−X188D−X232V−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020K−X023A−X043W−X118R−X128I−X129E−X159D−X188D、X024F−X118R−X128I−X129E−X159D、X020K−X024F−X062E−X116L−X118R−X188D、X020K−X062E−X116L−X188D、X062E−X116L−X118R−X213A、X020K−X023A−X062E−X116L−X188D、X062E−X116L−X118R−X188D、X020K−X062E−X116L−X213A、X020K−X023A−X062E−X116L、X020K−X062E−X188D−X213A、X020K−X062E、X020K−X024F−X062E−X116L−X188D、X020K−X043W−X062E−X116L−X188D、X020K−X024F−X062E−X188D−X213A、X062E−X116L−X188D−X213A、X020K−X062E−X116L、X020K−X023A−X062E−X116L−X188D−X213A、X023A−X024F−X062E−X116L−X213A、X022A−X043R−X103A−X104I−X128I−X12
9E−X159D−X188D−X232V−X245R−X248D、X022A−X043R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D−X271F、X024F−X062E−X116L−X188D、X022A−X024R−X103A−X104I−X118R−X128I−X129E−X159D−X188D−X232V−X248D、X023A−X062E−X116L−X188D、X043W−X062E−X116L、X020K−X023A−X116L−X188D、X043W−X062E−X116L−X188D、X024F−X062E−X116L、X062E−X116L−X188D、及びX022A−X024R−X103A−X104I−X128I−X159D−X188D−X232V−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX024R−X086W−X118R、X024R−X078R−X086W−X243F、X024R−X033S−X086S−X087N−X209A、X033S−X118R、X024R−X078R−X086W−X118R−X270T、X024R−X033S−X086W−X118R、X078R−X086W−X243F、X033S−X078R−X086W−X118R−X209A、X033S−X078R−X209A、X086W−X118R−X243F、X024R−X086W、X078R−X086W−X235F、X024R−X118R、X024R−X086R、X101G−X103A−X104I−X232V、X024R−X033S−X078R−X086W−X118R、X024R−X118R−X209A、X209A−X241R、X033S−X086W−X243F、X033S−X172V−X209A、X118R−X209A−X243F、X024R−X086S−X141G、X024R−X118R−X209A−X243F、X024R−X033S−X086S−X085N−X235F、X024R−X033S−X133V、X024R−X033S−X078R−X086W、X024R−X086W−X209A、X024R−X241R、X033S−X118R−X243F、X024R−X235F、X024R−X078R−X086W、X024R−X118R−X209A−X235F、X024R−X209A−X241R、X033S−X118R−X241R、X086W−X118R−X209A、X033S−X118R−X159D−X209A、X033S−X078R−X086W、X024R−X086W−X243F、X118R−X209A、X024R−X086W−X118R−X203I、X078R−X209A−X235F、X024R−X033S−X241R、X078R−X118R、X033S−X118R−X209A−X243F、X021M−X024R−X033S、X024R−X033S−X086W、X033S−X235F、X078R−X086W−X209A、X024R−X033S−X209A−X235F、X033S−X086W−X118R、X024R−X033S−X078R−X209A、X033S−X086W−X118R−X209A−X243F、X086W−X209A−X243F、X005S−X078R−X118R−X241R、X024R−X174T、X033S−X209A−X243F、X086W−X118R−X133V、X024R−X033S−X118R、X024R−X086W−X209A−X235F、X086W−X209A、X008T−X024R、X086W−X118R、X033S−X241R、X005S−X024R−X033S−X243F、X024R−X209A−X242P、X024R−X033S−X078R−X118R、X024R−X033S−X194T、X024R−X243F、X024R−X209A、X024R−X033S−X118R−X209A、X033S−X086W、X024R−X033S、X024R−X033S−X078R−X243F、X086W−X243F、X033S−X118D−X138V−X209A、X033S−X209A−X235F、X024R−X086R−X118R、X033S−X201S、X024R−X239Q、X033S−X118R−X209A−、X078R−X086W、X235F−X243F、X024R−X209A−X235F、X118R−X172V、X017Y−X024R−X033S−X086W、X033S−X148F、X024R−X118R−X235F、X033S−X078R、X033S−X243F、X024C−X033S、X118R−X194T、X033S−X209A、X118R−X209A−X235F、X024R−X033S−X209A−X243F、X024R−X033S−X235F、X024R−X033S−X118R−X235F、X024R−X141G、X024R−X274I、X024R−X033S−X209A、X086W−X235F、X024R−X209A−X243F、X004E−X033S−X078R、X086W−X209A−X235F、X015T−X033S、X033S−X086W−X156L−X209A、X024R−X118R−X243F−X269H、X209A−X235F、X024R−X247H、X024R−X033S−X228T、X078R−X235F、X024R−X033S−X174V−X235F、X024R−X235F−X243F、X024R−X033S−X235F−X241R、X024R−X033S−X151V、X024R−X104A、X033S−X048T、X012H−X104A−X118R、X118R−X235F、X033S−X253A、X143A−X209A、X024R−X033S−X243F、X033S−X239T、X209A−X243F、X024R−X033S−X129H−X184D−X253M、X024R−X085V−X086W−X118R−X235F、X024R−X272P、及びX024R−X269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX020R−X087D−X101G−X103A−X104I−X232V−X245R、X020R−X101G−X103A−X104I−X150L−X232V−X245R、X018R−X020R−X024R−X076D−X087D−X249R、X018R−X020R−X024R−X076D−X150L−X249R、X018R−X024R−X043R−X076D−X087D−X249R、X018R−X024R−X043R−X076D−X150L−X249R、X018R−X024R−X076D−X078R−X087D−X249R、X018R−X024R−X076D−X078R−X150L−X249R、X018R−X024R−X076D−X087D−X249R−X269R、X018R−X024R−X076D−X087D−X242R−X249R、X018R−X024R−X076D−X087D−X150L−X249R、X018R−X024R−X076D−X150L−X249R、X018R−X087D−X101G−X103A−X104I−X232V−X245R、X018R−X101G−X103A−X104I−X150L−X232V−X245R、X018R−X022R−X024R−X076D−X087D−X249R、X018R−X022R−X024R−X076D−X150L−X249R、X043R−X087D−X101G−X103A−X104I−X232V−X245R−X269R、X043R−X101G−X103A−X104I−X150L−X232V−X245R、X024R−X087D−X101G−X103A−X104I−X232V−X245R、X024R−X101G−X103A−X104I−X150L−X232V−X245R、X078R−X087D−X101G−X103A−X104I−X232V−X245R、X078R−X101G−X103A−X104I−X150L−X232V−X245R、X087D−X101G−X103A−X104I−X232V−X245R−X269R、X101G−X103A−X104I−X150L−X232V−X245R−X249R、X101G−X103A−X104I−X150L−X232V−X245R−X269R、X022R−X087D−X101G−X103A−X104I−X232V−X245R、X018R−X024R−X043D−X076D−X150L−X249R、X043R−X087D−X101G−X103A−X104I−X232V−X245R、X022R−X101G−X103A−X104I−X150L−X232V−X245R、X018R−X024R−X043D−X076D−X087D−X249R、X018R−X024R−X076D−X087D−X249R、X018R−X024R−X076D−X150L−X242R−X249R、X043R−X101G−X103A−X104I−X150L−X232V−X245R−X269R、X076D−X101G−X103A−X104I−X150L−X232V−X245R、X087D−X101G−X103A−X104I−X232V−X242R−X245R、X101G−X103A−X104I−X150L−X232V−X245R、X076D−X087D−X101G−X103A−X104I−X232V−X245R、X087D−X101G−X103A−X104I−X232V−X245R、及びX101G−X103A−X104I−X150L−X232V−X242R−X245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX024R−X101G−X103A−X104I−X129Q−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X130A−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129Q−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129Q−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129Q−X130A−X158E−X183D−X188D
−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129Q−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129Q−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129Q−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R、及びX024R−X027R−X101G−X103A−X104I−X128L−X129Q−X130A−X158E−X188D−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101G−X103A−X104I−X232V−X222Q−X245R、X101G−X103A−X104I−X158E−X188D−X222S−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X188D−X222Q−X232V−X245R−X248D−X249R、X076D−X101G−X103A−X104I−X232V−X222Q−X245R、X101G−X103A−X104I−X232V−X222S−X245R、X076D−X101G−X103A−X104I−X232V−X222S−X245R、及びX076D−X101G−X103A−X104I−X158E−X188D−X222S−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX024R−X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129Q−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X130A−X158E−X183D−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X130A−X158E−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X129Q−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X128L−X130A−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X130A−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X129Q−X158E−X188D−X232V−X245R−X248D−X249R−X271G、X101G−X103A−X104I−X129Q−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X130A−X158E−X188D−X217E−X232V−X245R−X248D−X249R、X024R−X101G−X103A−X104I−X128L−X158E−X183D−X188D−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X129Q−X158E−X188D−X217E−X232V−X245R−X248D−X249R、及びX024R−X101G−X103A−X104I−X128L−X130A−X158E−X188D−X232V−X245R−X248D−X249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX1R、X2W、X2M、X2R、X2A、X2S、X3R、X4R、X4C、X4S、X8A、X9F、X9W、X9A、X10S、X10M、X10H、X10A、X12R、X12F、X14K、X14F、X14Q、X15R、X15F、X16S、X17R、X17M、X17F、X18R、X18K、X20F、X20R、X20K、X22Y、X22A、X22R、X22V、X22Q、X22W、X22L、X23F、X23S、X23A、X24W、X24R、X24H、X24F、X24Q、X24L、X25V、X25F、X25R、X26F、X27V、X27F、X27L、X27R、X28N、X28E、X28A、X29T、X30E、X31F、X33D、X33G、X33S、X34P、X35M、X36F、X36R、X36T、X38L、X38F、X38R、X40L、X40W、X40N、X40R、X40T、X40H、X42I、X43D、X43I、X43R、X43M、X43F、X43W、X43S、X43A、X45T、X46R、X48R、X50C、X51H、X51W、X51F、X52F、X52E、X52N、X55Y、X57R、X59R、X59A、X59F、X60A、X60Q、X60P、X62E、X62Q、X63I、X63V、X63T、X63P、X63D、X63M、X63H、X63Q、X63E、X63A、X63S、X64F、X64T、X68C、X68A、X69N、X69P、X69W、X69T、X71G、X72C、X74C、X75F、X75A、X75R、X75E、X76D、X78I、X78R、X78N、X79W、X79Q、X81R、X82V、X82T、X82F、X82M、X82R、X85M、X86L、X86I、X86W、X89P、X89T、X89V、X89G、X89W、X89H、X89F、X89L、X89I、X91N、X91F、X92F、X94N、X99G、X99F、X99M、X99T、X99P、X100I、X100S、X100N、X100Q、X101N、X101A、X101G、X101P、X101F、X101E、X101T、X101D、X102H、X102N、X102E、X102T、X102A、X103G、X103D、X103N、X104D、X104E、X104I、X104L、X105Q、X105E、X105T、X106F、X106V、X106G、X106E、X106T、X106D、X106A、X107F、X107M、X108G、X108I、X109M、X111V、X111I、X112V、X112L、X112Q、X114G、X115K、X115R、X116A、X116K、X116L、X117F、X118I、X118R、X119C、X120F、X120A、X120R、X121E、X121F、X123G、X123E、X124S、X128F、X128H、X128I、X128L、X128Q、X128N、X128M、X128D、X129E、X132E、X132A、X138G、X144R、X147L、X148I、X158E、X158E、X159E、X159C、X160D、X166D、X166E、X167W、X175V、X177C、X181A、X182R、X183F、X183I、X183D、X183R、X183M、X185E、X185I、X185V、X186H、X186K、X188R、X188E、X188D、X192H、X192W、X194V、X194F、X194E、X197F、X198L、X198F、X203E、X203C、X208S、X209N、X209F、X209E、X209S、X209H、X209G、X209T、X209L、X210R、X210V、X210L、X211R、X211Q、X212I、X212M、X212F、X213A、X214F、X215F、X215N、X215D、X215H、X215E、X216F、X216A、X217N、X217E、X217D、X218P、X218D、X218E、X224A、X224G、X227I、X230E、X231I、X231C、X233C、X234F、X235F、X236F、X236N、X238L、X238K、X238R、X239K、X239S、X239T、X239G、X239H、X239R、X239N、X239F、X240R、X241R、X242L、X242R、X243R、X243F、X244R、X246S、X248I、X248V、X248R、X249R、X249T、X250I、X251S、X251R、X252I、X252F、X252H、X252R、X253F、X253I、X253R、X254C、X256N、X258R、X260V、X260I、X262H、X262D、X263F、X265F、X267N、X267V、X267M、X269I、X269R、X270C、X271F、X271V、X271I、X271P、X271H、X271M、X271T、X271L、X271A、X272F、X272R、X272F、X273I、X273F、及びX274Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 前記サブチリシン変異体が、タンパク質分解活性を有する成熟型であり、かつX16S、X18R、X20R、X22A、X24R、X43R/D、X45T、X76D、X101A、X103G、X104L、X111V、X128N、X148I、X230E、X242R、及びX249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、請求項35に記載の単離されたサブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX1R、X230E、X271L、X115R、X20R、X249R、X235F、X27V/F/L、X75E、X82R、X18R、X269R、X43D、X43R、X76D、X45T、X212F、X242R、X24R、X78R、X9A、X22R、X121E、X244R、X28E、X30E、X4R、及びX241Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX062E−X158E、X103G−X158E、X128N−X158E、X016S−X158E、X104L−X158E、X089P−X158E、X111V−X158E、X022A−X158E、X101A−X158E、X148I−X158E、X129E−X158E、X022A−X089P、X016S−X089P、X062E−X089P、X062E−X271F、X158E−X271F、X186H−X271F、X129E−X271F、X111V−X271F、X209E−X271F、X016S−X271F、X188D−X271F、X022A−X271F、X159E−X271F、X104L−X271F、X101A−X271F、X089P−X271F、X128N−X271F、X103G−X271F、X148I−X271F、X249R−X271F、X062E−X159E、X016S−X159E、X128N−X159E、X148I−X159E、X111V−X159E、X089P−X159E、X022A−X159E、X129E−X159E、X103G−X159E、X104L−X159E、X158E−X159E、X101A−X159E、X158E−X249R、X111V−X249R、X129E−X249R、X062E−X249R、X016S−X249R、X186H−X249R、X148I−X249R、X159E−X249R、X101A−X249R、X188D−X249R、X104L−X249R、X209E−X249R、X022A−X249R、X128N−X249R、X103G−X249R、X089P−X249R、X022A−X111V、X101A−X111V、X016S−X111V、X104L−X111V、X062E−X111V、X103G−X111V、X089P−X111V、X016S−X148I、X062E−X148I、X022A−X148I、X129E−X148I、X104L−X148I、X103G−X148I、X128N−X148I、X101A−X148I、X089P−X148I、X111V−X148I、X016S−X062E、X022A−X062E、X062E−X129E、X022A−X129E、X128N−X129E、X016S−X129E、X101A−X129E、X104L−X129E、X089P−X129E、X103G−X129E、X111V−X129E、X062E−X186H、X128N−X186H、X101A−X186H、X022A−X186H、X016S−X186H、X158E−X186H、X089P−X186H、X129E−X186H、X159E−X186H、X103G−X186H、X104L−X186H、X111V−X186H、X148I−X186H、X062E−X101A、X022A−X101A、X016S−X101A、X089P−X101A、X062E−X103G、X022A−X103G、X016S−X103G、X101A−X103G、X089P−X103G、X062E−X128N、X016S−X128N、X022A−X128N、X101A−X128N、X104L−X128N、X089P−X128N、X103G−X128N、X111V−X128N、X111V−X188D、X062E−X188D、X016S−X188D、X148I−X188D、X022A−X188D、X128N−X188D、X101A−X188D、X104L−X188D、X089P−X188D、X129E−X188D、X159E−X188D、X186H−X188D、X103G−X188D、X158E−X188D、X016S−X022A、X016S−X104L、X022A−X104L、X101A−X104L、X062E−X104L、X103G−X104L、X089P−X104L、X159E−X209E、X111V−X209E、X101A−X209E、X016S−X209E、X128N−X209E、X148I−X209E、X129E−X209E、X062E−X209E、X022A−X209E、X103G−X209E、X158E−X209E、X188D−X209E、X104L−X209E、X089P−X209E、及びX186H−X209Eから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX018R−X241R、X020R−X241R、X024R−X241R、X009A−X241R、X020R−X241R、X004R−X241R、X043R−X241R、X078R−X241R、X022R−X241R、X115R−X241R、X001R−X241R、X212F−X241R、X082R−X241R、X018R−X244R、X024R−X244R、X078R−X244R、X020R−X244R、X212F−X244R、X009A−X244R、X082R−X244R、X001R−X244R、X043R−X244R、X022R−X244R、X004R−X244R、X115R−X244R、X241R−X244R、X242R−X244R、X001R−X004R、X009A−X022R、X018R−X022R、X020R−X022R、X004R−X022R、X001R−X022R、X024R−X242R、X018R−X242R、X004R−X242R、X020R−X242R、X212F−X242R、X082R−X242R、X078R−X242R、X001R−X242R、X009A−X242R、X022R−X242R、X115R−X242R、X043R−X242R、X241R−X242R、X018R−X212F、X022R−X212F、X004R−X212F、X024R−X212F、X001R−X212F、X115R−X212F、X020R−X212F、X009A−X212F、X043R−X212F、X078R−X212F、X082R−X212F、X009A−X078R、X020R−X078R、X024R−X078R、X022R−X078R、X018R−X078R、X004R−X078R、X001R−X078R、X043R−X078R、X022R−X024R、X020R−X024R、X018R−X024R、X001R−X024R、X004R−X024R、X009A−X024R、X004R−X009A、X001R−X009A、X242R−X269R、X024R−X269R、X020R−X269R、X022R−X269R、X249R−X269R、X212F−X269R、X043R−X269R、X244R−X269R、X001R−X269R、X018R−X269R、X078R−X269R、X009A−X269R、X115R−X269R、X241R−X269R、X004R−X269R、X082R−X269R、X018R−X043R、X020R−X043R、X004R−X043R、X022R−X043R、X009A−X043R、X001R−X043R、X024R−X043R、X009A−X018R、X004R−X018R、X001R−X018R、X024R−X082R、X009A−X082R、X018R−X082R、X001R−X082R、X078R−X082R、X020R−X082R、X022R−X082R、X004R−X082R、X043R−X082R、X043R−X249R、X020R−X249R、X004R−X249R、X018R−X249R、X009A−X249R、X212F−X249R、X022R−X249R、X024R−X249R、X115R−X249R、X001R−X249R、X082R−X249R、X242R−X249R、X241R−X249R、X244R−X249R、X078R−X249R、X018R−X115R、X020R−X115R、X022R−X115R、X078R−X115R、X009A−X115R、X004R−X115R、X001R−X115R、X082R−X115R、X043R−X115R、X024R−X115R、X009A−X020R、X018R−X020R、X004R−X020R、X001R−X020R、X009A−X271L、X020R−X271L、X024R−X271L、X244R−X271L、X241R−X271L、X043R−X271L、X022R−X271L、X249R−X271L、X212F−X271L、X115R−X271L、X242R−X271L、X078R−X271L、X004R−X271L、X269R−X271L、X001R−X271L、X018R−X271L、及びX082R−X271Lから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101G−X103A−X104I、X22A−X101A−X209E、S103G−L111V−G159E、X22A−X103G−X159E、X22A−X111V−X159E、X22A−X128N−X271F−X209E、X22A−X103G−X111V、X62E−X111V−X128N、X22A−X111V−X128N、X22A−X62E−X111V、X101A−X103G−X104L−X188D、X101G−X103A−X104I−X159D、X101A−X103G−X104L−X128N、X22A−X101A−X159E、X101A−X103G−X104L、X101A−X103G−X104L−X159E、X22A−X101A−X103G−X104L、X101A−X103G−X104L−X209E、X22A−X209E−X271F、X22A−X101A−X271F、及びX101A−X209E−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX103A−X104I−X159D−X232V−X236H−X245R−X248D−X252K、X101G−X104I−X159D−X232V−X236H−X245R−X248D−X252K、X101G−X103A−X159D−X232V−X236H−X245R−X248D−X252K、X101G−X103A−X104L−X2
32V−X236H−X245R−X248D−X252K、X101G−X103A−X104L−X159D−X236H−X245R−X248D−X252K、X101G−X103A−X104L−X159D−X232V−X245R−X248D−X252K、X101G−X103A−X104L−X159D−X232V−X236H−X248D−X252K、X101G−X103A−X104L−X159D−X232V−X236H−X245R−X252K、及びX101G−X103A−X104L−X159D−X232V−X236H−X245R−X248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101G−X103A−X104I−X159D−X232V−X245R−X248D、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X238R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X248R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X253R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X24R、X101G−X103A−X104I−X159D−X232V−X245R−X248D−X76D、X101G−X103A−X104I−X159E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X159E−X232V−X245R−X248D−X271F、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X249R、X101G−X103A−X104I−X158E−X232V−X245R−X248D−X271F、X22A−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X249R、X22A−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271F、X62E−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X249R、及びX62E−X101G−X103A−X104I−X159D−X232V−X245R−X248D−X271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX20R−X43R−X249R、X20R−X22R−X43R、X20R−X43R−X242R、X20R−X43R−X271L、X20R−X43R−X244R、X20R−X24R−X43R−X242R、X9A−X22R−X78R−X212F−X241R、X9A−X20R−X43R−X212F、X9A−X43R−X212F、X20R−X43R−X212F、X20R−X22R−X43R−X212F、X24R−X78R−X212F、X9A−X43R−X78R、X9A−X43R−X78R−X242R、X9A−X20R−X43R−X78R、X20R−X24R−X43R−X78R−X242R、X22R−X24R−X78R−X212F、X9A−X20R−X43R−X78R−X242R、X20R−X43R−X78R−X249R、X20R−X43R−X78R、X9A−X78R−X212F、X9A−X22R−X43R−X78R、X9A−X20R−X24R−X43R、X9A−X22R−X78R−X212F、X4R−X9A−X22R−X78R−X212F、X20R−X24R−X43R、X1R−X9A−X43R、X20R−X24R−X43R−X115R、X9A−X24R−X43R、X20R−X22R−X24R−X43R、X1R−X24R−X43R、X9A−X20R−X24R−X43R−X242R、X9A−X20R−X22R−X78R−X212F、X9A−X24R−X43R−X244R、X9A−X24R−X43R−X242R、X4R−X9A−X22R−X24R−X212F、及びX22R−X24R−X43Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX101G−X103A−X104I−X232V−X245R−X248D、X101G−X103A−X104I−X159D−X232V−X245R、X101G−X103A−X104I−X159R−X232V−X245R−X248D、X101G−X103A−X104I−X159D−X232V−X245R−X248R、X101G−X103A−X104I−X232V−X245R、X101G−X103A−X104I−X232V−X245R−X248R、X101G−X103A−X104I−X159R−X232V−X245R−X248R、及びX101G、X103A、X104I、X232V、X236H、X245R、及びX252Kから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつX16S、X22A、X24R、X62E、X76D、X89P、X101A/G、X103G/A、X104L/I、X111V、X128N、X129E、X232V、X148I、X158E、X159D/E、X166D、X186H、X188D、X209E、X236H、X238R、X245R、X248D/R、X249R、X252K/R、X253R、及びX271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有する成熟型であり、かつN062E−A158E、S103G−A158E、S128N−A158E、A016S−A158E、V104L−A158E、E089P−A158E、L111V−A158E、T022A−A158E、S101A−A158E、L148I−A158E、P129E−A158E、T022A−E089P、A016S−E089P、N062E−E089P、N062E−E271F、A158E−E271F、R186H−E271F、P129E−E271F、L111V−E271F、Y209E−E271F、A016S−E271F、S188D−E271F、T022A−E271F、G159E−E271F、V104L−E271F、S101A−E271F、E089P−E271F、S128N−E271F、S103G−E271F、L148I−E271F、H249R−E271F、N062E−G159E、A016S−G159E、S128N−G159E、L148I−G159E、L111V−G159E、E089P−G159E、T022A−G159E、P129E−G159E、S103G−G159E、V104L−G159E、A158E−G159E、S101A−G159E、A158E−H249R、L111V−H249R、P129E−H249R、N062E−H249R、A016S−H249R、R186H−H249R、L148I−H249R、G159E−H249R、S101A−H249R、S188D−H249R、V104L−H249R、Y209E−H249R、T022A−H249R、S128N−H249R、S103G−H249R、E089P−H249R、T022A−L111V、S101A−L111V、A016S−L111V、V104L−L111V、N062E−L111V、S103G−L111V、E089P−L111V、A016S−L148I、N062E−L148I、T022A−L148I、P129E−L148I、V104L−L148I、S103G−L148I、S128N−L148I、S101A−L148I、E089P−L148I、L111V−L148I、A016S−N062E、T022A−N062E、N062E−P129E、T022A−P129E、S128N−P129E、A016S−P129E、S101A−P129E、V104L−P129E、E089P−P129E、S103G−P129E、L111V−P129E、N062E−R186H、S128N−R186H、S101A−R186H、T022A−R186H、A016S−R186H、A158E−R186H、E089P−R186H、P129E−R186H、G159E−R186H、S103G−R186H、V104L−R186H、L111V−R186H、L148I−R186H、N062E−S101A、T022A−S101A、A016S−S101A、E089P−S101A、N062E−S103G、T022A−S103G、A016S−S103G、S101A−S103G、E089P−S103G、N062E−S128N、A016S−S128N、T022A−S128N、S101A−S128N、V104L−S128N、E089P−S128N、S103G−S128N、L111V−S128N、L111V−S188D、N062E−S188D、A016S−S188D、L148I−S188D、T022A−S188D、S128N−S188D、S101A−S188D、V104L−S188D、E089P−S188D、P129E−S188D、G159E−S188D、R186H−S188D、S103G−S188D、A158E−S188D、A016S−T022A、A016S−V104L、T022A−V104L、S101A−V104L、N062E−V104L、S103G−V104L、E089P−V104L、G159E−Y209E、L111V−Y209E、S101A−Y209E、A016S−Y209E、S128N−Y209E、L148I−Y209E、P129E−Y209E、N062E−Y209E、T022A−Y209E、S103G−Y209E、A158E−Y209E、S188D−Y209E、V104L−Y209E、E089P−Y209E、及びR186H−Y209Eから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、N018R−W241R、G020R−W241R、S024R−W241R、S009A−W241R、G020R−W241R、V004R−W241R、N043R−W241R、S078R−W241R、T022R−W241
R、G115R−W241R、A001R−W241R、S212F−W241R、L082R−W241R、N018R−V244R、S024R−V244R、S078R−V244R、G020R−V244R、S212F−V244R、S009A−V244R、L082R−V244R、A001R−V244R、N043R−V244R、T022R−V244R、V004R−V244R、G115R−V244R、W241R−V244R、S242R−V244R、A001R−V004R、S009A−T022R、N018R−T022R、G020R−T022R、V004R−T022R、A001R−T022R、S024R−S242R、N018R−S242R、V004R−S242R、G020R−S242R、S212F−S242R、L082R−S242R、S078R−S242R、A001R−S242R、S009A−S242R、T022R−S242R、G115R−S242R、N043R−S242R、W241R−S242R、N018R−S212F、T022R−S212F、V004R−S212F、S024R−S212F、A001R−S212F、G115R−S212F、G020R−S212F、S009A−S212F、N043R−S212F、S078R−S212F、L082R−S212F、S009A−S078R、G020R−S078R、S024R−S078R、T022R−S078R、N018R−S078R、V004R−S078R、A001R−S078R、N043R−S078R、T022R−S024R、G020R−S024R、N018R−S024R、A001R−S024R、V004R−S024R、S009A−S024R、V004R−S009A、A001R−S009A、S242R−N269R、S024R−N269R、G020R−N269R、T022R−N269R、H249R−N269R、S212F−N269R、N043R−N269R、V244R−N269R、A001R−N269R、N018R−N269R、S078R−N269R、S009A−N269R、G115R−N269R、W241R−N269R、V004R−N269R、L082R−N269R、N018R−N043R、G020R−N043R、V004R−N043R、T022R−N043R、S009A−N043R、A001R−N043R、S024R−N043R、S009A−N018R、V004R−N018R、A001R−N018R、S024R−L082R、S009A−L082R、N018R−L082R、A001R−L082R、S078R−L082R、G020R−L082R、T022R−L082R、V004R−L082R、N043R−L082R、N043R−H249R、G020R−H249R、V004R−H249R、N018R−H249R、S009A−H249R、S212F−H249R、T022R−H249R、S024R−H249R、G115R−H249R、A001R−H249R、L082R−H249R、S242R−H249R、W241R−H249R、V244R−H249R、S078R−H249R、N018R−G115R、G020R−G115R、T022R−G115R、S078R−G115R、S009A−G115R、V004R−G115R、A001R−G115R、L082R−G115R、N043R−G115R、S024R−G115R、S009A−G020R、N018R−G020R、V004R−G020R、A001R−G020R、S009A−E271L、G020R−E271L、S024R−E271L、V244R−E271L、W241R−E271L、N043R−E271L、T022R−E271L、H249R−E271L、S212F−E271L、G115R−E271L、S242R−E271L、S078R−E271L、V004R−E271L、N269R−E271L、A001R−E271L、N018R−E271L、及びL082R−E271Lから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020R−N043R、G020K−N062E、S024F−N116L、G020K−S024F、S024R−A174T、S024R−G118R、S024R−K235F、S024R−P086R、S024R−P086W、S078R−G118R、T033S−G118R、T033S−K235F、Y209A−W241R、G020R−N076D、N018R−Q245R、S024R−R045T、A232V−Q245R、G118R−A172V、G118R−A194T、I008T−S024R、K235F−N243F、N018R−S103A、N018R−V104I、P086W−G118R、P086W−N243F、P086W−Y209A、S024C−T033S、S024R−A232V、S024R−N243F、S024R−P239Q、S024R−S101G、S024R−S141G、S024R−T033S、S024R−T274I、S024R−Y209A、S078R−P086W、S101G−A232V、T033S−L148F、T033S−P086W、T033S−P201S、T033S−S078R、T033S−W241R、T033S−Y209A、A230E−H249R、A232V−H249R、G118R−K235F、N076D−Q245R、P086W−K235F、S024R−R247H、S024R−V104A、S078R−K235F、S101G−H249R、S103A−A232V、T033S−A048T、T033S−P239T、T033S−T253A、T143A−Y209A、Y209A−K235F、N018R−R045T、Y209A−N243F、S024R−A272P、S024R−R269C、S101G−V104I、V104I−A232V、N076D−H249R、及びS024R−N076Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020R−N076D、S024R−R045T、A230E−H249R、N018R−R045T、N018R−Q245R、S101G−A232V、S024R−A232V、A232V−Q245R、S024R−S101G、N018R−V104I、N018R−S103A、S101G−H249R、A232V−H249R、S103A−A232V、N076D−Q245R、S101G−V104I、V104I−A232V、N076D−H249R、S024R−N076D、S024F−N116L、G020K−S024F、G020K−N062E、T033S−G118R、S024R−P086W、S024R−G118R、S024R−P086R、Y209A−W241R、S024R−W241R、S024R−K235F、G118R−Y209A、S078R−G118R、T033S−K235F、S024R−A174T、P086W−Y209A、I008T−S024R、P086W−G118R、T033S−W241R、S024R−N243F、S024R−Y209A、T033S−P086W、S024R−T033S、P086W−N243F、T033S−P201S、S024R−P239Q、S078R−P086W、K235F−N243F、G118R−A172V、T033S−L148F、T033S−S078R、T033S−N243F、S024C−T033S、G118R−A194T、T033S−Y209A、S024R−S141G、S024R−T274I、P086W−K235F、A015T−T033S、Y209A−K235F、S024R−R247H、S078R−K235F、S024R−V104A、T033S−A048T、G118R−K235F、T033S−T253A、T143A−Y209A、T033S−P239T、Y209A−N243F、S024R−A272P、及びS024R−R269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、V004R−S009A−G020R−S242R、G020R−N043R−W241R、G020R−S242R−N269R、V004R−S009A−G020R−N043R、V004R−G020R−H249R、N018R−S024R−V244R、S009A−T022R−S212F−W241R、G020R−N043R−N269R、N018R−S024R−S242R、V004R−S009A−N043R−W241R、G020R−N043R−V244R、G020R−T022R−S242R、V004R−G020R−N043R、V004R−S009A−G020R−N043R−S242R、G020R−N043R−S242R、G020R−N043R−S242R−H249R、G020R−S212F−H249R、V004R−S009A−W241R、A001R−S009A−N043R、G020R−N043R−H249R、S009A−G020R−N043R−W241R、G020R−T022R−N043R、G020R−H249R−N269R、G020R−T022R−W241R、V004R−S009A−S024R−N043R−W241R、S009A−N043R−S078R、V004R−G020R−S024R−V244R、G020R−T022R−S078R−S242R、G020R−S024R−S242R−H249R、V004R−S009A−S078R−W241R、S009A−N043R−S078R−S242R、V004R−G020R−S024R、S009A−N043R−S212F、G020R−N043R−S212F、S024R−S078R−S212F、S009A−G020R−S024R−N043R、S009A−T022R−N043R−S078R、G020R−T022R−S212F−W241R、G020R−N043R−S212F−W241R、S009A−N043R−W241R、G020R−N043R−E271L、G020R−T022R−S078R−W241R、G020R−S024R−N043R−S242R、G020R−T022R−N043R−W241R、S009A−G020R−N043R−S212F、V004R−S009A−G020R−S024R−S242R、G020R−N043R−H249R−E271L、G020R−T022R−S024R−S242R、S009A−T022R−S078R−S212F、G020R−N043R−S242R−E271L、S009A−T022R−S078R−S212F−W241R、V004R−G020R−S024R−H249R、G020R−T022R−E271L、G020R−T022R−N043R−S212F、V004R−G020R−S024R−N043R−S242R、V004R−G020R−S024R−N043R、V004R−S009A−T022R−S078R−S212F、G020R−T022R−S078R−S212F−W241
R、及びG020R−T022R−N269Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、N018R−G020R−N043D−R045T−A230E、N018R−N043R−R045T−S242R−H249R、S024R−N043D−H249R、N018R−G020R−R045T、G020R−S024R−N076D−H249R、S024R−N043R−A230E−S242R、N018R−S024R−N043D−A230E、G020R−N076D、N018R−S024R−N043D−N076D−H249R、S024R−N043R−N076D−H249R、N018R−S024R−R045T−S242R、G020R−N043D−N076D−A230E−H249R、G020R−N043R−R045T−S242R、N018R−S024R−N076D−H249R、N018R−G020R−S024R−N043D−R045T−L233I−S242R、S024R−N043R−A230E、N018R−G020R−N043D、N043R−S242R−H249R、G020R−N043R−R045T−A230E、N043R−N076D−S242R−H249R、G020R−S024R−R045T−A230E−S242R、S024R−R045T−N076D−A230E−S242R−H249R、S024R−R045T、S024R−N043R−R045T−N076D−A230E−H249R、N018R−S024R−N043D−R045T−H249R、N018R−N043R−R045T−H249R、S024R−N043R−S242R、N018R−G020R−N043R−N076D−H249R、G020R−S024R−N043D−H249R、G020R−N043R−A230E−S242R、G020R−N043R−S242R、N018R−N043R−N076D−A230E、G020R−S024R−N043D−S242R、G020R−N043R−A230E、N018R−G020R−N043R−N076D−S242R−H249R、N043D−R045T−N076D−H249R、N018R−N043R−S242R−H249R、N018R−G020R−N043R−R045T−S242R、N018R−G020R−N043D−A230E−S242R、G020R−S024R−N043R−R045T−H249R、S024R−N043R−H249R、G020R−S024R−K27E−N043R−N076D−A230E、S024R−N043R−R045T−S242R、N018R−G020R−S024R−N043R−R045T−N076D−A230E、G020R−N043R−N076D−A230E−H249R、N018R−N043R−R045T−S242R、G020R−S242R−H249R、N018R−N043R−N076D−A230E−S242R−H249R、N018R−S024R−N076D、G020R−S024R−K27R−N043D−S242R−H249R、N018R−G020R−S024R−N043D−N076D−S242R、N018R−N043R−N076D−S242R−H249R、N018R−S024R−N043D−A230E−H249R、N018R−G020R−N043D−H249R、N018R−G020R−N043D−R045T−N076D−S242R、S024R−N043R−N076D−A230E−S242R、G020R−S024R−T38I−N043R−R045T−N076D−S242R−H249R、N018R−G020R−N043R、N018R−S024R−R045T−A230E−S242R、N018R−G020R−H249R、S024R−N043R−N076D、N018R−G020R−S024R−N043R−R045T−N076D−H249R、N018R−N043D−R045T−N076D−S242R−H249R、S024R−N043D−S242R−H249R、N018R−G020R−S024R−N043D−R045T−S242R、G020R−S024R−N043R−N076D、N018R−G020R−N043D−R045T−A230E−S242R、G020R−S024R−N043R−R045T−N076D−S242R−H249R、N018R−N043R−R045T−N076D−S242R、N018R−G020R−N043R−N076D−A230E−S242R、N018R−S024R−N043D−H249R、N018R−S024R−N043R−R045T−A230E−H249R、N018R−G020R−N043R−R045T−N076D−H249R、N018R−S024R−S242R、N018R−N043R−R045T−N076D−A230E−S242R、R045T−S242R−H249R、N018R−S024R−N043D−S242R、N018R−G020R−N043D−R045T−S240P、S024R−N043R−R045T−S242R−H249R、N018R−S024R−V30S−L31S−D32I−T33Q−G34V−I35F、N018R−G020R−N043R−N076D、G020R−N043D−R045T−N076D−S242R−H249R、N018R−S024R−N043D−A230E−S242R、N018R−S024R−N043D−S242R−H249R、S024R−N043D−R045T−S242R−H249R、N043R−A230E−H249R、S024R−N043R−N076D−A230E−H249R、G020R−S024R−N043D−N076D−H249R、S024R−R045T−S242R−A273V、G020R−S024R−R045T−N076D−S242R−H249R、N018R−S024R−N043D−N076D−S242R、N018R−N043R−N076D−A230E−H249R、N018R−G020R−N043R−R045T−H249R、N018R−N043R−R045T−A230E−S242R、G020R−S024R−N043D−R045T−A230E−S242R、N018R−N043D−A230E−H249R、N018R−N043R−N076D−S242R、N018R−G020R−N076D、N018R−G020R−N043D−N076D−S242R−H249R、G020R−S024R−N043D−N076D−S242R−H249R、N043D−S242R−H249R、N018R−G020R−S024R−N043R−N076D、N018R−G020R−N043D−R045T−N076D−H249R、N018R−G020R−N043R−R045T−N076D−A230E−H249R、N018R−N076D−S242R、G020R−N043R−H249R、N018R−N076D−S242R−H249R、N018R−S024R−R045T−A230E−H249R、A230E−H249R、N018R−R045T−H249R、G020R−N043R−N076D、N043R−R045T−H249R、N018R−N043D−N076D−S242R−H249R、N043R−N076D−H249R、N018R−R045T、G020R−N076D−A230E−S242R、G020R−S024R−N043D−R045T、S024R−N043D−N076D−S242R−H249R、G020R−R045T−H249R、N043R−N076D−S153A−H249R、N043R−N076D−A230E−H249R、N018R−N043D−N076D−H249R、及びG020R−N043R−N076D−V227Iから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S101G−S103A−V104I−A232V−Q236H−Q245R−N252K、S101G−S103A−V104I−A232V−Q245R−N248R、S101G−S103A−V104I−G159R−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R−N248R、S101G−S103A−V104I−A232V−Q245R、S101G−S103A−V104I−G159D−A232V−Q245R、及びS101G−S103A−V104I−A232V−Q245R−N248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−L148I−A158E−A232V−Q245R−N248D、A016S−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A
158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−A158E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−G159E−S188D−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−S188D−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−A158E−G159E−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−Q245R−N248D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−G159E−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−S128N−P129E−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128N−A158E−G159E−S188D−A232V−Q245R−N248D、T022A−S024K−S101G−S103A−V104I−S128N−A158E−G159E−A232V−Q245R−N248D、S101G−S103A−V104I−P129E−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、T022A−S101G−S103A−V104I−L148I−S188D−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−S128N−P129E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−S128N−P129E−A158E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−L148I−A158E−S188D−A232V−Q245R−N248D、T022A−S024R−S101
G−S103A−V104I−L148I−A158E−S188D−A232V−Q245R−N248D、S101G−S103A−V104I−L148I−G159E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D、及びS101G−S103A−V104I−S128N−P129E−A158E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、T022A−S024R−S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−G159E−S188D−A232V−Q245R−N248D−H249R、T022A−S024R−S101G−S103A−V104I−A158E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−L148I−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D−H249R、A016S−S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129E−G159E−A232V−N238R−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−P129E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−L148I−A158E−A232V−Q245R−N248D、S024R−S101G−S103A−V104I−P129E−S188D−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−N238R−Q245R−N248D、T022A−S101G−S103A−V104I−A158E−G159E−A232V−N238R−Q245R−N248D、T022A−S024R−S101G−S103A−V104I−P129E−A158E−A232V−Q245R−N248D、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、T022A−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248D−H249R、及びS024R−S101G−S103A−V104I−A158E−G159E−A232V−Q245R−N248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、V104L−S128N−A158E−R186H−H249R、S128N−A158E−S188D−H249R、N062E−S128N−A158E−G159E−E271F、N062E−A158E−S188D−H249R−E271F、N062E−A158E−R186H−H249R−E271F、S128N−A158E−S188D−Y209E−E271F、N062E−G159E−S188D−H249R、A016S−N062E−A158E−R186H−H249R、N062E−A158E−G159E−H249R、S101A−S128N−A158E−Y209E−H249R、S128N−A158E−R186H−E271F、N062E−A158E−S188D−H249R、N062E−A158E−R186H−E271F、N062E−A158E−R186H−H249R、N062E−S101A−R186H−H249R、N062E−S101A−A158E−R186H−E271F、N062E−V104L−A158E−S188D−H249R−E271F、N062E−G159E−R186H−H249R、N062E−G159E−H249R、S128N−A158E−R186H−H249R、S128N−A158E−S188D−E271F、N062E−A158E−H249R、N062E−R186H−S188D−H249R−E271F、S128N−A158E−Y209E−、N062E−S101A−A158E−H249R、V104L−S128N−A158E−R186H−E271F、N062E−S101A−A158E−R186H−H249R−E271F、A016S−N062E−A158E−H249R、N062E−S101A−G159E−H249R、S128N−A158E−R186H−S188D−E271F、S101A−S128N−A158E−R186H−E271F、N062E−S101A−S188D−H249R、S101A−V104L−A158E−R186H−S188D−H249R、N062E−G159E−H249R−E271F、S128N−A158E−G159E−E271F、A016S−N062E−V104L−A158E−R186H−E271F、T022A−S128N−A158E−H249R、S128N−A158E−H249R、N062E−S101A−V104L−A158E−R186H−E271F、A016S−N062E−A158E−R186H−E271F、V104L−S128N−A158E−H249R、V104L−S128N−A158E−S188D−H249R、T022A−N062E−A158E、N062E−S101A−S188D−H249R−E271F、N062E−A158E−H249R−E271F、V104L−S128N−A158E−R186H−S188D−E271F、N062E−S101A−R186H−E271F、N062E−V104L−G159E−H249R、N062E−R186H−H249R、N062E−S101A−R186H−H249R−E271F、S101A−A158E−R186H−S188D−H249R、N062E−S101A−R186H、S101A−S128N−P129E−R186H−H249R、S101A−S103G−A158E−R186H−H249R、A016S−N062E−V104L−R186H−S188D−E271F、V104L−A158E−R186H−H249R、S101A−S128N−A158E−S188D−Y209E−E271F、N062E−S101A−R186H−S188D−E271F、A016S−N062E−A158E−H249R−E271F、N062E−S128N−A158E、N062E−S128N−G159E−H249R、N062E−S101A−A158E−S188D−H249R、S101A−S128N−A158E−H249R、N062E−A158E−R186H−S188D−H249R、A016S−V104L−A158E−R186H−E271F、N062E−L148I−G159E、N062E−S101A−A158E−R186H−H249R、N062E−S101A−R186H−S188D−H249R、V104L−A158E−R186H−S188D−H249R、N062E−S101A−V104L−R186H−S188D−E271F、T022A−S101A−A158E−R186H−H249R、S101A−S128N−A158E−Y209E、A158E−R186H−S188D−H249R−E271F、V104L−A158E−R186H−S188D−H249R−E271F、S101A−V104L−A158E−R186H−H249R、V104L−A158E−H249R、S101A−V104L−S128N−A158E−R186H−E271F、A016S−V104L−S188D−H249R、S101A−V104L−A158E−R186H−S188D−E271F、V104L−S128N−G159E−E271F、V104L−A158E−R186H−H249R−E271F、A158E−R186H−H249R、S101A−A158E−R186H−H249R、V104L−A158E−S188D−H249R−E271F、A016S−S128N−A158E−R186H、V104L−S128N−R186H−S188D−H249R、A016S−S101A−S128N−R186H、A016S−N062E−S128N−R186H−E271F、A016S−S128N−R186H−E271F、S128N−P129E−R186H、A158E−R186H−H249R−E271F、A016S−A158E−H249R、A016S−A158E−R186H−H249R、A016S−T022A−A158E−R186H−E271F、E089P−S101A−P129E−R186H、T022A−S128N−A158E−R186H、S101A−V104L−S128N−A158E−R186H、T022A−S128N−R186H−S188D−、N062E−V104L−A158E−R186H−S188D−H249R、T022A−A158E−R186H−H249R−E271F、T022A−V104L−A158E−H249R、S101A−L111V−P129E、A016S−A158E−H249R−E271F、A016S−L111V−S188D−、T022A−V104L−R186H−S188D−H249R、及びV104L−L148I−S188D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、A001R−S101G−S103A−V104I−A232V−Q245R、V004R−S101G−S103A−V104I−A232V−Q245R、N043R−S
101G−S103A−V104I−A232V−Q245R−E271L、S078R−S101G−S103A−V104I−A232V−Q245R、V004R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−A232V−Q245R、S101G−S103A−V104I−A232V−Q245R−E271L、G020R−N043R−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−S101G−S103A−V104I−A232V−Q245R、G020R−G025R−N116A−Y167W、N018R−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−A232V−Q245R、S078R−S103N−S106G−Y167W−Q236N、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101A−H120F−A194F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−S212F−A232V−Q245R、G020R−S144R−N185I−L233C−Q236N、G023A−S078R−S216F−Q236N−H249R、S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−G115R−A232V−Q245R、P052N−S078R−S103N−L148I−T213A、N018R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G025R−E089I−N116A−P239S−A270C、S024R−S101G−S103A−V104I−A232V−Q245R、L148I−T213A−N252R、S024R−G025R−N183D−Y192W−P239S、G046R−A194F−S212M、V104L−L217E−T224A−H249R−N252R、G023A−Y091F−V121F−Y192W−Q236N、S101G−S103A−V104I−A232V−V244R−Q245R、S099F−S144R−Y167W−N252R、S101G−S103A−V104I−A232V−Q245R−H249R、N043R−S101G−S103A−V104I−A232V−Q245R、T022W−S078R−Y167W−S212M−A270C、V121F−N252R−A270C、G020R−S103N−S216F−Q236N−N252R、N043R−S101G−S103A−V104I−A232V−Q245R−H249R、G023A−P052N−Y192W−I198L−N252R、G025R−G046R−V121F、S024R−S078R−V104L−N116A−N183D、G046R−Q059A−S103N−G211Q−S212M、G020R−P052N−N062Q−Y091F−Y192W、G023A−P052N−S144R−Y192W−S216F、S101G−S103A−V104I−A232V−S242R−Q245R、P052N−S103N−N116A−L148I−Y192W、E089I−N116A−N117F−T224A−H249R、S144R−G211Q−N238L−P239S−H249R、N043A−N062Q−A194F−G211Q、G020R−S024R−P052N−Q059A−S216F、S024R−Y167W−T224A−H249R、T057R−Y167W−H249R、G025R−S103N−R186K−A194F−T224A、S105T−S128N−S144R−L148I−S212M、G020R−Q059A−S144R−Y192W−T224A、S024R−N043A−N117F−A194F−G211Q、N117F−A194F−T213A−A270C、S078R−Y091F−V121F−L233C−N252R、T057R−S099F−S105T−I198L−T213A、G023A−Y091F−S101A−I198L−N252R、N062Q−S103N−V121F−S144R−H249R、N043R−S101G−S103A−V104I−A232V−S242R−Q245R、G023A−S024R−N117F−S212M−S216F、V104L−T213A−S216F、A194F−G211Q−Q236N、N062Q−S103N−N117F−A194F、S024R−N062Q−V104L−S106G−H249R、T057R−E089I−I198L、G046R−Q059A−S106G−L217E−H249R、N117F−T213A−A215F、S101A−H120F−Y192W−A215F−T224A、N043A−T057R−N117F−S144R−N183D、G046R−N183D−N238L、G025R−N043A−E089I−N117F、S078R−V104L−T213A−A215F−T224A、Y091F−S099F−S101A−S105T−Y167W、S106G−N117F−N238L、G046R−E089I−Y091F−S101A−N116A、G020R−N062Q−E089I−R186K−S212M、T057R−S099F−V121F−N185I−Y192W、G046R−E089I−Y192W−L233C−A270C、E089I−N117F−N185I−A215F−L233C、P052N−V104L−N183D−S216F−H249R、S078R−S099F−N116A−R186K−T224A、G025R−S105T−S128N−S144R−A270C、S105T−G211Q−S216F、S024R−G046R−Y091F−V121F、S106G−N185I−S216F−Q236N、N062Q−S101A−Q236N−N252R−A270C、G025R−N043A−Y091F−I198L−A270C、G020R−G023A−V104L−Y192W−L233C、S024R−N043A−S105T−S106G−I198L、G020R−E089I−L217E、S024R−Y091F−I198L−A215F−P239S、G046R−E089I−S099F−R186K−S212M、V104L−H120F−R186K−S216F−N252R、T022W−A194F−T213A−L233C−N238L、S099F−S105T−S106G−A194F−S212M、E089I−S105T−N116A−A215F−S216F、G025R−N116A−H120F−T224A−A270C、N043A−Q059A−S101A−S216F−T224A、T057R−N183D−Q236N、G025R−N062Q−S128N−S144R−N185I、S103N−H120F−Y167W−I198L−L233C、T022W−E089I−S216F、S024R−S106G−N116A−S212M−T224A、G020R−P052N−S101A−I198L−L233C、E089I−Y091F−N185I−G211Q−A270C、L111I−A215F−P239S、S024R−N116A−R186K−L233C−Q236N、及びG023A−S103N−S106G−S212M−A215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020R−T022W−S078R−S101A−S103A−V104I−N116S−T213A−A215F−A232V−Q245R、N018R−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、G020R−T22W−S101G−S103A−V104I−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−V104I−A232V−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−H249R、N018R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S103A−A232V−H249R、N018R−S101G−V104I−A232V−Q245R、G020R−S024R−S101G−S103A−V104I−L217E−A232V−Q245R−H249R、N018R−T22K−N043D−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101G−S103A−V104I−G211Q−A232V−Q245R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A232V、N018R−S024R−N076D−N116A−A215F−H249R、N018R−N043R−R045T−S101G−S103A−V104I−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−N116A−G211Q−H249R、N043R−R045T
−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S101G−S103A−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A232V−Q245R、N018R−S101G−V104I−A232V−H249R、G020R−T22W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−I198L−H249R、S024R−S101G−S103A−V104I−A232V−Q245R、G020R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−V104I−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A215F−A232V−Q245R、S024R−S103A−V104I−H249R、N018R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S101G−V104I−Q245R、G020R−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、S024R−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−Q245R、S024R−S103A−Q245R、S024R−S103A−V104I−Q245R、G020R−S078R−S101G−A232V−Q245R、N018R−S024R−N076D−V104I−H249R、N018R−S024R−V104I−H249R、S024R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−A215F−H249R、R019H−G020R−T022W−S078R−S101G−S103A−V104I−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S103A−V104I−A232V−Q245R、N018R−S103A−V104I−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−S024R−S101G−V104I−A232V、S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−T213A−H249R、N018R−S024R−S101G−V104I、G020R−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−Q245R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−T213A−A215F−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−A215F−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101A−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I−H249R、G020R−T22W−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−N076D−V104I−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101G−V104I−A232V−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、A001T−N018R−S024R−N076D−N116A−T213A−H249R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S101G−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−S101G−I198L−A215F−A232V−Q245R、N018R−S024R−N076D−T213A−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、S024R−A232V−Q245R、N018R−S024R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−H249R、S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N116A−T213A−A215F−H249R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−A215V−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−H249R、G020R−S103A−V104I−A232V−Q245R、G020R−T22W−S101A−S103A−V104I−G211Q−A215F−A232V−Q245R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−A232V−Q245R、N018R−T22W−S024R−N076D−I198L−A215F−H249R、G020R−T022W−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−G211Q−T213A−A215F−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−A215F−H249R、G020R−R045T−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−T180A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S101G−S103A−V104I、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−S103A−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N1
83D−A232V−Q245R、N018R−S024R−N076D−G211Q−H249R、G020R−S101A−S103A−V104I−T213A−A215F−A232V−Q245R、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−G211Q−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−S024R−N076D−A232V−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−Q245R、S024R−V104I−Q245R、S101G−A232V、G020R−T22W−S101A−S103A−V104I−N116A−G211Q−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−A232V−Q245R、G020R−T022W−S078R−S101A−S103A−V104I−I198L−A232V−Q245R、S024R−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−G211Q−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−H249R、S024R−S101G−V104I−H249R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−V104I、G020R−T022W−S078R−S101A−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−G020R−T22W−S024R−N076D−N116A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−A232V−Q245R、Q012H−G020R−S078R−S101G−S103A−V104I−I198L−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−S024R−N076D−T213A−H249R、S024R−V104I−H249R、N018R−T022W−S024R−N076D−G211Q−H249R、N018R−N076D−S103A−V104I−H249R、N043R−N076D−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N183D−G211Q−T213A−A232V−Q245R−E271G、N018R−T022W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、G020R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、R045T−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T22W−S024R−N076D−S101A−N116A−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、S024R−S103A−M175L−A232V−H249R、N018R−S024R−N076D−N116A−T213A−H249R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−Q245R、G020R−S024R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−A232V、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、S024R−N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−H249R、N018R−S024R−N076D−I198M−G211Q−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−A215F−H249R、N018R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S103A−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−A215F−H249R−V268G、N018R−T022W−S024R−N076D−S101A−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、S101G−S103A−V104I−Q245R、N018R−N076D−S101G−A232V−Q245R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−H249R、S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、R045T−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−S103A−A232V、N018R−S024R−N076D−S101A−G211Q−H249R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N043R−R045T−N076D−S076T−S101G−S103A−V104I−A232V−Q245R−A273T、N018R−G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101G−A232V、A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−V234I−Q245R、S024R−N076D−S103A−V104I−Q245R、G020R−S078R−S101A−S103A−V104I−G211Q−T213A−A232V−Q245R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−A272V、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S103A−V104I−A232V、G020R−T022W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S024R−N043R−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、G020R−T022W−S078R−S101G−S103A−V104I−G211Q−T213A−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N116A−M117I−N183D−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T22W−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−A232V−Q245R、N018R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−Y209H−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、S024R−N076D−S101G−M175L−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G
020R−S078R−S101A−S103A−V104I−N116A−N183D−I198L−A215F−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S024R−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−A215F−H249R、S024R−N076D−V104I−Q245R、K027R−N043R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−G211Q−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T22W−S024R−N076D−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−G211Q−A215F−H249R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−V104I、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S078R−S101A−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−I198L−G211Q−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−H249R、N018R−N076D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、G020R−T022W−S078R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−A114T−T213A−A215F−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、N018R−T022K−N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−S078R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V、N018R−S024R−N076D−N116A−H249R、G020R−S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−I198L−T213A−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T22W−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、G020R−S101G−S103A−V104I−N183D−G211Q−A232V−Q245R−、N018R−S024R−N076D−S101A−I198L−T213A−H249R、N018R−S024R−N076D−S101A−I198L−H249R、N018R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−S078R−S101G−S103A−V104I−N116A−A131V−N183D−T213A−A232V−Q245R、N018R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−G211Q−H249R、N076D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−S101G−Q245R、S024R−N076D−S101G−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、S024R−S101G、N018R−T22W−S024R−N076D−T213A−A215F−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N183D−I198L−T213A−A215F−A232V−Q245R、N018R−N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−I198L−G211Q−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−G020R−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−V104I、N018R−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−L088I−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−G020R−S101G−S103A−V104I−A232V−Q245R−H249R、S101G−S103A−V104I−A232V−Q245R−H249R−N269R、S024R−N076D−Q245R、N018R−G020R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−G211Q−A215F−H249R、N043D−S101G−S103A−V104I−A232V−Q245R、G020R−T22W−S078R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−I198L−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−T213A−H249R、G020R−T022W−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N043R−R045T−S078R−S101G−S103A−V104I−N218S−A232V−Q245R、N018R−S103A、G020R−T22W−S101G−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−H249R、N018R−T022W−S024R−N076D−G211Q−T213A−H249R、S024R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、K027R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−V104I、S101G−S103A−V104I−A232V−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A215F−H249
R、N018R−S024R−N076D−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−H249R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R−R275S、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、V004M−N018R−S024R−N076D−N116A−I198L−G211Q−T213A−H249R、V104I−A232V−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−T274I、G020R−S101A−S103A−V104I−T213A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−S103A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−A215F−H249R−A270V、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101G−S103A−V104I−N183D−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−T213A−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−T22W−S024R−N076D−N116A−I198L−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101G−S103A−V104I−A232V、S101G−H249R、S024R−N076D−S101G−S103A−V104I−M175L−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−N269S、N018R−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−T213A−A215F−H249R−T260K、N018R−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−V104I−Q245R、S024R−N076D−S103A−H249R、N018R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、G020R−S024R−R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−A272D、N018R−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N018R−T22W−S024R−N076D−S101A−I198L−H249R、N018R−T022W−S024R−N076D−N116A−I198L−H249R、S024R−N076D−S101G−S103A−A232V、S024R−S103A−V104I、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、G020R−S101G−S103A−V104I−N116A−N183D−A232V−Q245R、S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、G020R−T022W−S101A−S103A−V104I−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−N043R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−T213A−H249R、N018R−S024R−N076D−N116A−N183D−T213A−H249R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N076D−S103A−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、S103A−V104I−Q245R、N018R−T022W−S024R−N076D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−A215F−H249R、A016T−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−A215F−H249R、N043R−N076D−S101G−S103T−V104I−A232V−Q245R−H249R−N269R、G020R−S078R−S101A−S103A−V104I−G115E−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−S024R−N076D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−H249R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−S024R−N076D−S101G、N076D−S101G−A232V−Q245R、N018R−N076D−S101G−S103A−V104I−Q245R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−A215F−H249R、N018R−V104I−A232V、N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S101G−A232V−H249R、S103A−A232V−Q245R、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S024R−N076D−S103A−V104I−H249R、S024R−S101G−S103A−V104I、G020R−S101G−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−A131T−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−G020R−S024R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−S101G−S103A−V104I−Q245R−H249R、N018R−N076D−A232V−H249R、N018K−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−N269R、N018R−G020R−S024R−N043D−N076D−S078R−S101G−S103A−V10
4I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N116A−T213A−A215F−H249R−L267I、A232V−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N076D−V104I−Q245R、N018R−G020R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−S101A−G211Q−T213A−H249R、S024R−S101G−S103A−A232V、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−A215F−A232V−Q245R、N018R−S024R−N076D−N116A−I198L−G211Q−H249R、S103A−A232V−H249R、N018R−G020R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A232V−Q245R−T274I、S024R−S103A−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−T213A−H249R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−T213A−H249R、S103A−A232V、N018R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−S101A−N116A−H249R、N018R−N043R−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−I198L−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−A215F−A232V−Q245R、N018R−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−A232V、N018R−T022W−S024R−N076D−S101A−N116A−H249R、G020R−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R−N263S、S024R−N076D−S101G−V104I−A232V−H249R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−H249R、N018R−S024R−N076D−S101A−V197A−T213A−A215F−H249R、S024R−S101G−S103A、N018R−S024R−N076D−S101A−N116A−G211Q−A215F−H249R、N043R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−V104I−A232V、N018R−S024R−N076D−N183D−G211Q−H249R、G020R−N043R−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−A150T−T213A−H249R、N018R−S024R−N076D−N183D−T213A−H249R、N018R−G020R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−H249R、S024R−N076D−A232V−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116T−I198L−A215F−H249R、N018R−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、R045T−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−H249R、G020R−S101G−S103A−V104I−N116A−N183D−T213A−A232V−Q245R、N076D−S101G−S103A−Q245R、G020R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−N116A−N183D−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−H249R、N018R−T22W−S024R−N076D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N076D−S101G−V104I−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N183D−H249R、N018R−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−G211Q−H249R、G020R−S101A−S103A−V104I−N116A−N183D−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−S101G−S103A−V104I−A232V−Q245R、N018R−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、G020R−S101A−S103A−V104I−N116A−N183D−G211Q−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−Y209H−H249R、N018R−S024R−N076D−N183D−I198L−T213A−A
215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−A215F−H249R、N076D−Q245R、N076D−S101G−V104I−Q245R、N018R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−T213A−H249R、G020R−S024R−N043R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、G020R−S101A−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、S101G−S103A−V104I、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N204D−T213A−H249R、N018R−T022W−S024R−N076D−N183D−I198L−H249R、N018R−S024R−N076D−S101A−N116A−N183D−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A209V−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−N116A−H249R、N018R−G020R−T022W−S024R−N076D−S101A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−I198L−T213A−H249R、N018R−G020R−S024R−N076D−S101A−G211Q−A215F−H249R−N269D、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101G−S103A−V104I−N183D−A215F−A232V−Q245R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−Y209H−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N076D−A232V−Q245R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−Q245R、N018R−G020R−T022W−S024R−N076D−T213A−H249R、G020R−S024R−N043D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−A215F−H249R、G020R−A090S−S101G−S103A−V104I−N116A−N183D−T213A−A215F−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043D−R045T−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−T213A−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、N018R−G020R−S024R−N043D−N076D−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−N043D−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−A232V−Q245R、R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−H249R、N018R−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−N043D−N076D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N076D−S103A−V104I−Q245R、N018R−G020R−S024R−N076D−S101A−N116A−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−S024R−N076D−S101G−Q245R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−A215F−H249R、N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−T213A−A215F−H249R、N076D−V104I−A232V−Q245R、K027R−N043R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S103A−V104I−L135I−A232V、N018R−G020R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−A215F−H249R、N076D−S101G−S103A−V104I−A232V−H249R、P005S−N018R−T022W−S024R−N076D−S101A−T213A−A215F−H249R、N018R−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−H249R、N018R−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N183D−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−A215F−H249R、N018R−G020R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、G020R−T022W−S101A−S103A−V104I−N183D−I198L−A215F−A232V−Q245R、N076D−S101G−S103A−V104I−H249R、N018R−G020R−S024R−N076D−N183D−I198L−A215F−H249R、N018R−G020R−T022W−S024
R−N076D−S101A−N183D−A215F−H249R、N018R−G020R−S024R−N076D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−S024R−N076D−G211Q−N243D−H249R、N018R−G020R−R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−N116A−I198L−G211Q−T213A−A215F−H249R、S024R−N076D−S101G、N018R−G020R−S024R−N076D−S101A−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N183D−A215F−H249R、N018R−N043D−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−Q245R、G020R−S024R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−N116A−I198L−G211Q−A215F−H249R−N269S、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、G020R−T022W−S101A−S103A−V104I−N183D−T213A−A215F−A232V−Q245R、N018R−S024R−N076D−A086V−S101A−N183D−I198L−G211Q−H249R、N018R−N076D−S101G−I198T−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−N183D−H249R−A248T、N018R−N076D−V104I−Q245R−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−H249R、N018R−G020R−S024R−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−H249R、N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N043R−R045T−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−N076D−S101G−V104I、G020R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−H249R、N043D−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−H249R、N018R−N076D−V104I、N018R−G020R−N043D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−T022W−S024R−N076D−N183D−G211Q−H249R、N018R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、S101G−V104I、N018R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−S101A−N183D−G211Q−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N116A−N183D−A215F−H249R−N263D、N018R−T022W−S024R−N076D−S101A−N183D−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−A215F−H249R、N018R−T022W−S024R−N076D−N116A−I198L−A215F−H249R−R269H、N018R−N043D−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−R045T−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−G211Q−H249R、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−H249R、G020R−T022W−S101G−S103A−V104I−N116A−N183D−I198L−G211Q−T213A−A215F−A232V−Q245R、V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N183D−I198L−H249R、N043D−R045T−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−N043R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−R045T−N076D−S078R−S101G−S103A−V104I−Y166F−A176P−A179V−N184T−A187P−A194P、N018R−T022W−S024R−D041E−N076D−S101A−S160T−N183D−G211Q−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−I198L−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−G211Q−A215F−H249R、S024R−N076D−V104I、N018R−N076D−S101G−A232V、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−A215F−H249R、N018R−S024R−L031F−N076D−N116A−N183D−G211Q−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−T213A−H249R−N269S、N018R−G020R−S024R−N076D−S101A−N116A−I198L−A215F−H249R、N018R−N043R−N076D−S078R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N114T−I198L−G211Q−A215F−H249R、S024R−N043R−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、S024R−N076D−S103A−V104I−A232V、N018R−G020R−T022W−S024R−N076D−S101A−I198L−G211Q−A215F−H249R、S101G−V104I−A232V、N018R−T022W−S024R−N076D−N183D−I198L−T213A−A215F−H249R、N018R−T022W−S024R−N076D−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N183D−T213A−H249R、N018R−S024R−N076D−S101A−N183D−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−G211Q−T213A−H249R、N018R−S078R−S
101G−S103A−V104I−A232V−Q245R−N269R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−G211Q−A215F−H249R−T260A、N076D−H249R、N018R−T022W−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N116A−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−T213A−H249R、N018R−G020R−T022W−S024R−N076D−N116A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N183D−H249R、N076D−V104I−H249R、G020R−T022W−S101A−S103A−V104I−N116A−N183D−G211Q−T213A−A215F−A232V−Q245R、S024R−N043R−R045T−S078R−S101G−S103A−V104I−L217E−A232V−Q245R、N018R−G020R−T022W−S024R−N076D−N183D−I198L−A215F−H249R、N018R−N076D−S101G−S103A、G020R−S024R−S101G−S103A−V104I−A232V−Q245R−N269R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R、S101G−S103A−A232V、S024R−N076D−S101G−A232V、N018R−T022W−S024R−N076D−S101A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−G211Q−A215F−H249R、N018R−G020R−S024R−N076D−N183D−I198L−H249R、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−G020R−S024R−N076D−N116A−A156V−N183D−G211Q−A215F−H249R−N269S、R045T−N076D−S101G−S103A−V104I−A232V−Q245R−H249R、N018R−G020R−S024R−N076D−S101A−N183D−I198L−H249R、N018R−G020R−T022W−S024R−N076D−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−G211Q−A215F−H249R、N018R−G020R−T022W−S024R−N076D−N116A−H249R、N018R−N076D−S101G、N018R−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N018R−G020R−T022W−S024R−N076D−S101A−N116A−I198L−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−H249R、N018R−N076D−A232V、N018R−G020R−S024R−N076D−S101A−A232V−Q245R、N018R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、N018R−T022W−S024R−N076D−N183D−T213A−A215F−H249R、N018R−S024R−N076D−S101A−N116A−G211Q−T213A−N237D−H249R、N018R−G020R−S024R−N076D−S101A−N116A−N183D−G211Q−H249R−R275S、N018R−T022W−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−A215F−H249R、S024R−N076D、N018R−S024R−N076D−N183D−G211Q−A215F−H249R、N018R−T022W−S024R−N076D−N116A−N183D−I198L−T213A−A215F−H249R、N076D−V104I−A232V−H249R、N018R−N076D−S103A−A232V、N018R−G020R−S024R−N076D−S101A−N116A−N183D−I198L−G211Q−T213A−H249R、N018R−G020R−S024R−N076D−S101A−N183D−T213A−H249R、N018R−G020R−S024R−N076D−S101A−D175E−N183D−G211Q−A215F−H249R、N018R−G020R−N043D−S078R−S101G−S103A−V104I−L217E−A232V−Q245R−A273E、G020R−S024R−N043D−R045T−N076D−S101G−S103A−V104I−A232V−Q245R、P005S−S101G−S103A−V104I−A232V−Q245R−H249R、S103A−V104I−A232V、N018R−G020R−S024R−V068A−N076D−S101A−N116A−T213A−A215F−H249R、N018R−T022W−S024R−N076D−S101A−I198L−A215F−H249R−R275S、N018R−S024R−N076D−N183D−I198L−G211Q−T213A−H249R、及びN043D−R045T−S101G−S103A−V104I−A232V−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、N018R−S024R−N043R−N076D−H249R−N269R、N018R−T022R−S024R−N043R−N076D−H249R、N018R−N043D−S101G−S103A−V104I−A232V−Q245R、G020R−N043D−S101G−S103A−V104I−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R−N269R、N043D−S078R−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、T022R−N043R−S101G−S103A−V104I−A232V−Q245R、N043R−S078R−S101G−S103A−V104I−A232V−Q245R、G020R−N076D−S101G−S103A−V104I−A232V−Q245R、N043R−N076D−S101G−S103A−V104I−A232V−Q245R、T022R−N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S078R−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043R−N076D−H249R、N018R−S024R−N076D−S242R−H249R、N018R−S024R−N076D−H249R−N269R、N018R−T022R−S024R−N076D−H249R、N018R−S024R−N076D−S078R−H249R、N018R−S024R−N043D−N076D−H249R−N269R、N018R−T022R−S024R−N043D−N076D−H249R、N018R−S024R−N043D−N076D−S078R−H249R、G020R−S101G−S103G−V104I−A232V−Q245R、G020R−S101G−S103A−V104L−A232V−Q245R、G020R−S101G−S103A−V104V−A232V−Q245R、G020R−S101G−S103S−V104I−A232V−Q245R、G020R−S101G−S103S−V104L−A232V−Q245R、G020R−S101S−S103S−V104I−A232V−Q245R、G020R−S101S−S103S−V104L−A232V−Q245R、G020R−S101A−S103A−V104L−A232V−Q245R、G020R−S101S−S103S−V104V−A232V−Q245R、G020R−S101S−S103A−V104I−A232V−Q245R、G020R−S101S−S103A−V104V−A232V−Q245R、G020R−S101S−S103G−V104I−A232V−Q245R、G020R−S101S−S103G−V104V−A232V−Q245R、G020R−S101A−S103A−V104V−A232V−Q245R、G020R−S101A−S103S−V104I−A232V−Q245R、G020R−S101A−S103S−V104V−A232V−Q245R、N018R−S024R−N043R−N076D−S078R−H249R、S024R−N043D−S101G−S103A−V104I−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R−H249R、S024R−N076D−S101G−S103A−V104I−A232V−Q245R、N076D−S101G−S103A−V104I−A232V−S242R−Q245R、N018R−G020R−S024R−N076D−L217E−H249R、N018R−S024R−N043R−N076D−L217E−H249R、N018R−S024R−N043D−N076D−S242R−H249R、N018R−G020R−S024R−N043R−N076D−H249R、G020R−S101A−S103G−V104V−A232V−Q245R、N043D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N076D−L217E−H249R−N269R、及びN018R−S024R−N076D−L217E−S242R−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020R−S101A−S103A−V104I−G118R−A232V−Q245R、G020R−S024R−N116A−T213A、N043R−S101A−N116A−A215F−N269R、S024R−N043R−S101A−N116A、S024R−N043R−S101A−N116A−A215F−N269R、G020R−S101G−S103A−V104I−A215F−A232V−Q245R、N043R−S101A−N269R、S024R−N043R−N116A−T213A−N269R、G020R−S024R−N043R−R045T−S101A−T213A、S024R−N043R−N116A−A215F−N269R、G020R−S024R−T213A−A215F、G020R−N116A−N269R、S024R−N116A−T213A−N269R、N043R−S101A−N116A−N269R、S101G−S103A−V104
I−N116A−T213A−A232V−Q245R−N269R、S024R−N043R−R045T−S101A−N116A−A215F−N269R、G020R−N043R−S101A−N269R、S101A−S103A−V104I−T213A−A232V−Q245R−N269R、S024R−A215F−N269R、N043R−S101A−N116A−T213A−A215F−N269R、N043R−S101A−T213A−N269R、G020R−S024R−N043R−R045T−N116A−T213A、S101G−S103A−V104I−A232V−Q245R−N269R、S024R−N043R−R045T−S101A−N116A−T213A−N269R、S024R−N043R−R045T−N269R、G020R−N043R−R045T−S101A−N269R、S024R−N043R−N116A−N269R、G020R−S024R−N043R−R045T、N043R−N116A−N269R、S024R−N043R−S101A−A215F−N269R、S024R−N043R−R045T−T213A−A215F−N269R、G020R−S024R−R045T−N269R、G020R−N043R−S101A−N116A−T213A−A215F、G020R−S101G−S103A−V104I−T213A−A215F−A232V−Q245R、G020R−S024R−R045T−N116A−N269R、G020R−S101A−N116A−N269R、S024R−N043R−A215F、G020R−S024R−T213A、S024R−N043R−S101A−A215F、G020R−S024R−N043R−R045T−N116A、G020R−S024R−N043R−R045T−S101A−N269R、G020R−S024R−S101A−A215F、G020R−S024R−N116A−T213A−A215F、G020R−S024R−N116A、G020R−S024R−S101A−N116A、N043R−T213A−A215F−N269R、S024R−S101A−N269R、S024R−N043R−N116A−A215F、G020R−T038A−N043R−S101A、G020R−S024R−N116A−A215F、S024R−N043R−S101A−T213A、P014L−G020R−S024R−N043R−R045T−S101A−A215F、G020R−S024R−A215F、G020R−N116A−A215F−N269R、G020R−R045T−N116A−N269R、G020R−S024R−N043R−R045T−A215F、及びG020R−S024R−N043R−R045T−N116A−T213A−A215Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、N043R−N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−N043R−N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F−E271F、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、N076D−S101G−S103A−V104I−A114V−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−N076D−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S024R−N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−N043R−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101A−S103A−V104I−A158E−S166D−S188D−L217E−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、及びN043R−N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、T022A−S101G−S103A−V104I−G159D−L217E−A232V−Q245R−N248D−E271F、T022A−N043R−S101G−S103A−V104I−G159D−S188D−L217E−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、N043R−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、N043R−N076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271F、S024R−S101G−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、S024R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N076D−S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R−E271F、S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、S101G−S103A−V104I−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−S188D−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R−E271F、N043R−N076D−S101A−S103A−V104I−A158E−S166D−S188D−A232V−Q245R−N248D−H249R、及びN076D−S101A−S103A−V104I−A158E−S188D−L217E−A232V−Q245R−N248D−H249R−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、H017R−T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−H249R−E271F、H017R−T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、T022A−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271F、T022A−S101G−G102A−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、及びT022A−N043R−N076D−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S101S−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S
101A−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103G−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101S−S103S−V104V−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103S−V104I−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104L−A158E−S188D−A232V−Q245R−N248D−H249R、S101A−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101G−S103S−V104L−G159E−A232V−Q245R−N248D−H249R、S101S−S103A−V104L−G159E−A232V−Q245R−N248D−H249R、S101A−S103G−V104V−G159E−A232V−Q245R−N248D−H249R、及びS101S−S103A−V104V−G159E−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、V026F−V051W−V104L−S106E、V026F−L031F−S078N−G102A−S160D、G020K−G100S−N116L−A158E−S166D−N243F、T033S−N043W−N218D−P239G−N243F、T022L−T038F−A048R−N062E−G100S−R186K、S101D−S103N−N116L−S144R−A215D、V104L−S105T−T213A−L217E−S256N、N043W−S101D−S212M−N243F、V026F−A048R−S105T−T213A−N218D−T224A、S024F−S101D−G118R−A215D−L250I−A272F、V121F−N185E−T224A−P239G、T022L−L031F−G102A−S128D−T224A−N243F、N062E−S078N−G102A−N116L−S144R−L250I、T022L−T038F−V121F−S160D−A272F、V026F−S078N−G159C−R186K−N243F、S024F−A048R−G118R−S166D−L217E、G023A−T038F−S078N−G100S−S212M−A215D、G100S−N116L−A158E−T213A、S078N−V104L−G118R−S128D、G102A−S103N−S105T−A194E、T022L−S078N−S128D−T213A、K027R−G100S−G118R−S160D−S188D−N243F、S024F−G102A−R186K−T213A−L217E−N243F、T033S−S105T−S188D−S216F、G023A−G100S−A194E−S212M、A048R−S128D−N185E−P239G、G020K−S024F−T033S−P129E−A194E、G020K−K027R−P129E−S166D−P239G、T022L−G023A−K027R−S101D−V104L−S216F、T033S−G118R−P129E−A194E−P239G、T022L−S078N−N116L−P129E−S256N、K027R−S101D−S103N−S105T−A272F、A048R−S078N−N116L−N185E−L217E−P239G、G023A−S024F−K027R−N062E、S024F−S103N−V104L−G118R−S188D、V026F−V104L−S256N−A272F、S024F−N043W−V104L−V121F−P129E、N062E−S078N−N116L−T224A、G023A−S024F−V051W−A158E、K027R−T038F−G102A−N116L、N062E−S078N−S144R−S212M、L031F−N116L−S256N−A272F、T022L−T033S−V104L−N116L−S160D−R186K、S024F−G118R−P129E−R186K−T213A、N043W−S105T−T213A−A215D−S216F、L031F−S105T−R186K−S188D、V026F−A194E−T213A−S256N、及びS103N−S160D−L250I−S256Nから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、T022A−S024R−S101D−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−S024R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−N043R−S101D−S103A−V104I−G159D−S188D−A232V−Q245R−N248D、T022A−S103A−V104I−G159D−S188D−A232V−N248D、T022A−S024R−S103A−V104I−G118R−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−N043R−N062E−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D、T022A−S024R−S101D−S103A−V104I−G118R−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S024R−N043R−S103A−V104I−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D−E271F、T022A−N043R−S103A−V104I−G118R−G159D−S188D−A232V−N248D−E271F、T022A−S103A−V104I−S128I−P129E−G159D−S188D−A232V−N248D−E271F、T022A−S103A−V104I−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−N043R−S103A−V104I−S128I−G159D−S188D−A232V−Q245R−N248D、T022A−S101D−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271F、T022A−S103A−V104I−G118R−P129E−G159D−S188D−A232V−Q245R−N248D−E271F、T022A−S024R−N043R−S103A−V104I−G118R−G159D−S188D−L217D−A232V−N248D、T022A−N062E−S103A−V104I−G118R−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S101D−S103A−V104I−G118R−P129E−G159D−S188D−L217D−A232V、T022A−S024R−S103A−V104I−G159D−S188D−L217D−A232V−N248D、T022A−S024R−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−L217D−A232V−N248D−E271F、及びT022A−S103A−V104I−G118R−G159D−S188D−L217D−A232V−Q245R−N248D−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020K−S024F−N062E−S188D−P239G、S024F−N062E−N116L−P239G、G020K−G023A−N062E−S188D、G020K−G023A−S024F−N062E−G118R−S188D−T213A、G020K−N043W−N062E−N116L−S188D−T213A−P239G、G023A−N062E−N116L−G118R、G023A−S024F−N062E−N116L−G118R、S024F−N116L、S024F−N062E−S188D−T213A、G023A−N062E−N116L−G118R−S188D−P239G、G020K−S024F−N062E、G020K−N043W−N062E−N116L−P239G、S024F−N062E−N116L−T213A−P239G、G020K−S024F−N043W−N062E−N116L−T213A、G020K−G023A−S024F−N062E−N116L−S188D−T213A、S024F−N
062E−S188D−P239G、G023A−N043W−N062E−N116L−G118R−T213A、N062E−S188D−P239G、G020K−S024F−N062E−P239G、S024F−N116L−G118R−S188D−P239G、G020K−G023A−N062E−N116L−G118R−T213A、G020K−G023A−S024F−N062E−S188D−T213A−P239G、S024F−N043W−G118R−S188D、G023A−S024F−N116L−G118R−S188D−T213A、G020K−G023A−N043W−N116L−S188D−T213A−P239G、G023A−S024F−N116L−S188D−P239G、G023A−N043W−N116L−G118R−S188D、G023A−S024F−G118R−S188D−P239G、G023A−S024F−N043W−N062E−N116L−G118R、G020K−N043W−S188D−T213A、S024F−N062E−G118R−P239G、G023A−N043W−S188D−T213A、G020K−S024F−N043W−N062E−N116L−G118R−S188D−P239G、G020K−N116L−S188D−P239G、G020K−N043W−N062E−G118R、G020K−N043W−N116L−S188D−T213A、G020K−S024F、G023A−N043W−N116L−P239G、G023A−S024F−N043W−N116L−G118R−S188D−P239G、G020K−G023A−N043W−T213A、及びG023A−S024F−N062E−G118R−T213A−P239Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020K−G023A−N043W−G118R−S128I−P129E−G159D−S188D、S024F−G118R−S128I−P129E−G159D、G020K−S024F−N062E−N116L−G118R−S188D、G020K−N062E−N116L−S188D、N062E−N116L−G118R−T213A、G020K−G023A−N062E−N116L−S188D、N062E−N116L−G118R−S188D、G020K−N062E−N116L−T213A、G020K−G023A−N062E−N116L、G020K−N062E−S188D−T213A、G020K−N062E、G020K−S024F−N062E−N116L−S188D、G020K−N043W−N062E−N116L−S188D、G020K−S024F−N062E−S188D−T213A、N062E−N116L−S188D−T213A、G020K−N062E−N116L、G020K−G023A−N062E−N116L−S188D−T213A、G023A−S024F−N062E−N116L−T213A、T022A−N043R−S103A−V104I−S128I−P129E−G159D−S188D−A232V−Q245R−N248D、T022A−N043R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D−E271F、S024F−N062E−N116L−S188D、T022A−S024R−S103A−V104I−G118R−S128I−P129E−G159D−S188D−A232V−N248D、G023A−N062E−N116L−S188D、N043W−N062E−N116L、G020K−G023A−N116L−S188D、N043W−N062E−N116L−S188D、S024F−N062E−N116L、N062E−N116L−S188D、及びT022A−S024R−S103A−V104I−S128I−G159D−S188D−A232V−N248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S087R−S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S101G−S103A−V104I−Q109R−A232V−Q245R、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R−E271V、S101G−S103A−V104I−Q109R−S212P−A232V−Q245R、N076D−S87R−S103A−V104I−S212P−E271V、N076D−S103A−V104I−Q109R、N076D−S103A−V104I−S212P−E271V、N076D−S103A−V104I−Q109R−Q245R、及びN076D−S103A−V104I−S212P−Q245L−E271Vから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S024R−P086W−G118R、S024R−S078R−P086W−N243F、S024R−T033S−P086S−S087N−Y209A、T033S−G118R、S024R−S078R−P086W−G118R−A270T、S024R−T033S−P086W−G118R、S078R−P086W−N243F、T033S−S078R−P086W−G118R−Y209A、T033S−S078R−Y209A、P086W−G118R−N243F、S024R−P086W、S078R−P086W−K235F、S024R−G118R、S024R−P086R、S101G−S103A−V104I−A232V、S024R−T033S−S078R−P086W−G118R、S024R−G118R−Y209A、Y209A−W241R、T033S−P086W−N243F、T033S−A172V−Y209A、G118R−Y209A−N243F、S024R−P086S−S141G、S024R−G118R−Y209A−N243F、S024R−T033S−P086S−S085N−K235F、S024R−T033S−A133V、S024R−T033S−S078R−P086W、S024R−P086W−Y209A、S024R−W241R、T033S−G118R−N243F、S024R−K235F、S024R−S078R−P086W、S024R−G118R−Y209A−K235F、S024R−Y209A−W241R、T033S−G118R−W241R、P086W−G118R−Y209A、T033S−G118R−G159D−Y209A、T033S−S078R−P086W、S024R−P086W−N243F、G118R−Y209A、S024R−P086W−G118R−V203I、S078R−Y209A−K235F、S024R−T033S−W241R、S078R−G118R、T033S−G118R−Y209A−N243F、L021M−S024R−T033S、S024R−T033S−P086W、T033S−K235F、S078R−P086W−Y209A、S024R−T033S−Y209A−K235F、T033S−P086W−G118R、S024R−T033S−S078R−Y209A、T033S−P086W−G118R−Y209A−N243F、P086W−Y209A−N243F、P005S−S078R−G118R−W241R、S024R−A174T、T033S−Y209A−N243F、P086W−G118R−A133V、S024R−T033S−G118R、S024R−P086W−Y209A−K235F、P086W−Y209A、I008T−S024R、P086W−G118R、T033S−W241R、P005S−S024R−T033S−N243F、S024R−Y209A−S242P、S024R−T033S−S078R−G118R、S024R−T033S−A194T、S024R−N243F、S024R−Y209A、S024R−T033S−G118R−Y209A、T033S−P086W、S024R−T033S、S024R−T033S−S078R−N243F、P086W−N243F、T033S−G118D−A138V−Y209A、T033S−Y209A−K235F、S024R−P086R−G118R、T033S−P201S、S024R−P239Q、T033S−G118R−Y209A−、S078R−P086W、K235F−N243F、S024R−Y209A−K235F、G118R−A172V、H017Y−S024R−T033S−P086W、T033S−L148F、S024R−G118R−K235F、T033S−S078R、T033S−N243F、S024C−T033S、G118R−A194T、T033S−Y209A、G118R−Y209A−K235F、S024R−T033S−Y209A−N243F、S024R−T033S−K235F、S024R−T033S−G118R−K235F、S024R−S141G、S024R−T274I、S024R−T033S−Y209A、P086W−K235F、S024R−Y209A−N243F、V004E−T033S−S078R、P086W−Y209A−K235F、A015T−T033S、T033S−P086W−S156L−Y209A、S024R−G118R−N243F−R269H、Y209A−K235F、S024R−R247H、S024R−T033S−A228T、S078R−K235F、S024R−T033S−A174V−K235F、S024R−K235F−N243F、S024R−T033S−K235F−W241R、S024R−T033S−A151V、S024R−V104A、T033S−A048T、Q012H−V104A−G118R、G118R−K235F、T033S−T253A、T143A−Y209A、S024R−T033S−N243F、T033S−P239T、Y209A−N243F、S024R−T033S−P129H−N184D−T253M、S024R−A085V−P086W−G118R−K235F、S024R−A272P、及びS024R−R269Cから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、G020R−S087D−S101G−S103A−V104I−A232V−Q245R、G020R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−G020R−S024R−N076D−S087D−H249R、N018R−G020R−S024R−N076D−V150L−H249R、N018R−S024R−N043R−N076D−S087D−H249R、N018R−S024R−N043R−N076D−V150L−H249
R、N018R−S024R−N076D−S078R−S087D−H249R、N018R−S024R−N076D−S078R−V150L−H249R、N018R−S024R−N076D−S087D−H249R−N269R、N018R−S024R−N076D−S087D−S242R−H249R、N018R−S024R−N076D−S087D−V150L−H249R、N018R−S024R−N076D−V150L−H249R、N018R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−T022R−S024R−N076D−S087D−H249R、N018R−T022R−S024R−N076D−V150L−H249R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R−N269R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R、S024R−S087D−S101G−S103A−V104I−A232V−Q245R、S024R−S101G−S103A−V104I−V150L−A232V−Q245R、S078R−S087D−S101G−S103A−V104I−A232V−Q245R、S078R−S101G−S103A−V104I−V150L−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−Q245R−N269R、S101G−S103A−V104I−V150L−A232V−Q245R−H249R、S101G−S103A−V104I−V150L−A232V−Q245R−N269R、T022R−S087D−S101G−S103A−V104I−A232V−Q245R、N018R−S024R−N043D−N076D−V150L−H249R、N043R−S087D−S101G−S103A−V104I−A232V−Q245R、T022R−S101G−S103A−V104I−V150L−A232V−Q245R、N018R−S024R−N043D−N076D−S087D−H249R、N018R−S024R−N076D−S087D−H249R、N018R−S024R−N076D−V150L−S242R−H249R、N043R−S101G−S103A−V104I−V150L−A232V−Q245R−N269R、N076D−S101G−S103A−V104I−V150L−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−S242R−Q245R、S101G−S103A−V104I−V150L−A232V−Q245R、N076D−S087D−S101G−S103A−V104I−A232V−Q245R、S087D−S101G−S103A−V104I−A232V−Q245R、及びS101G−S103A−V104I−V150L−A232V−S242R−Q245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、及びS024R−K027R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S101G−S103A−V104I−A232V−M222Q−Q245R、S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−S188D−M222Q−A232V−Q245R−N248D−H249R、N076D−S101G−S103A−V104I−A232V−M222Q−Q245R、S101G−S103A−V104I−A232V−M222S−Q245R、N076D−S101G−S103A−V104I−A232V−M222S−Q245R、及びN076D−S101G−S103A−V104I−A158E−S188D−M222S−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S130A−A158E−N183D−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−S128L−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−S130A−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−P129Q−A158E−S188D−A232V−Q245R−N248D−H249R−E271G、S101G−S103A−V104I−P129Q−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S130A−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、S024R−S101G−S103A−V104I−S128L−A158E−N183D−S188D−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−P129Q−A158E−S188D−L217E−A232V−Q245R−N248D−H249R、及びS024R−S101G−S103A−V104I−S128L−S130A−A158E−S188D−A232V−Q245R−N248D−H249Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S101G−S103A−V104I、T22A−S101A−Y209E、S103G−L111V−G159E、T22A−S103G−G159E、T22A−L111V−G159E、T22A−S128N−E271F−Y209E、T22A−S103G−L111V、N62E−L111V−S128N、T22A−L111V−S128N、T22A−N62E−L111V、S101A−S103G−V104L−S188D、S101G−S103A−V104I−G159D、S101A−S103G−V104L−S128N、T22A−S101A−G159E、S101A−S103G−V104L、S101A−S103G−V104L−G159E、T22A−S101A−S103G−V104L、S101A−S103G−V104L−Y209E、T22A−Y209E−E271F、T22A−S101A−E271F、及びS101A−Y209E−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、S103A−V104I−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−V104I−G159D−A232V−Q236H−Q245R
−N248D−N252K、S101G−S103A−G159D−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−A232V−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−Q236H−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q245R−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−N248D−N252K、S101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N252K、及びS101G−S103A−V104L−G159D−A232V−Q236H−Q245R−N248Dから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - タンパク質分解活性を有する単離されたサブチリシン変異体であって、S101G−S103A−V104I−G159D−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N238R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N248R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−T253R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−S24R、S101G−S103A−V104I−G159D−A232V−Q245R−N248D−N76D、S101G−S103A−V104I−G159E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−G159E−A232V−Q245R−N248D−E271F、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−H249R、S101G−S103A−V104I−A158E−A232V−Q245R−N248D−E271F、T22A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R、T22A−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271F、N62E−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−H249R、及びN62E−S101G−S103A−V104I−G159D−A232V−Q245R−N248D−E271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- タンパク質分解活性を有する単離されたサブチリシン変異体であって、A1R、A230E、E271L、G115R、G20R、H249R、K235F、K27V/F/L、L75E、L82R、N18R、N269R、N43D、N43R、N76D、R45T、S212F、S242R、S24R、S78R、S9A、T22R、V121E、V244R、V28E、V30E、V4R、W241R、G20R−N43R−H249R、G20R−T22R−N43R、G20R−N43R−S242R、G20R−N43R−E271L、G20R−N43R−V244R、G20R−S24R−N43R−S242R、S9A−T22R−S78R−S212F−W241R、S9A−G20R−N43R−S212F、S9A−N43R−S212F、G20R−N43R−S212F、G20R−T22R−N43R−S212F、S24R−S78R−S212F、S9A−N43R−S78R、S9A−N43R−S78R−S242R、S9A−G20R−N43R−S78R、G20R−S24R−N43R−S78R−S242R、T22R−S24R−S78R−S212F、S9A−G20R−N43R−S78R−S242R、G20R−N43R−S78R−H249R、G20R−N43R−S78R、S9A−S78R−S212F、S9A−T22R−N43R−S78R、S9A−G20R−S24R−N43R、S9A−T22R−S78R−S212F、V4R−S9A−T22R−S78R−S212F、G20R−S24R−N43R、A1R−S9A−N43R、G20R−S24R−N43R−G115R、S9A−S24R−N43R、G20R−T22R−S24R−N43R、A1R−S24R−N43R、S9A−G20R−S24R−N43R−S242R、S9A−G20R−T22R−S78R−S212F、S9A−S24R−N43R−V244R、S9A−S24R−N43R−S242R、V4R−S9A−T22R−S24R−S212F、及びT22R−S24R−N43Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有し、かつS101G−S103A−V104I−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R、S101G−S103A−V104I−G159R−A232V−Q245R−N248D、S101G−S103A−V104I−G159D−A232V−Q245R−N248R、S101G−S103A−V104I−A232V−Q245R、S101G−S103A−V104I−A232V−Q245R−N248R、S101G−S103A−V104I−G159R−A232V−Q245R−N248R、S101G、S103A、V104I、A232V、Q236H、及びQ245Rから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有し、かつA16S、T22A、S24R、N62E、N76D、E89P、S101A/G、S103G/A、V104L/I、L111V、S128N、P129E、A232V、L148I、A158E、G159D/E、R186H、S188D、Y209E、Q236H、Q245R、N248D/R、H249R、N252K/R、T253R、及びE271Fから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。
- 単離されたサブチリシン変異体であって、タンパク質分解活性を有し、かつA1R、Q2S、Q2M、Q2A、Q2R、Q2W、S3R、V4R、V4S、V4C、I8A、S9A、S9F、S9W、R10S、R10A、R10H、R10M、Q12F、Q12R、P14K、P14F、P14Q、A15R、A15F、A16S、H17R、H17M、H17F、N18R、N18K、G20F、G20K、G20R、T22A、T22R、T22Y、T22V、T22Q、T22L、T22W、G23A、G23S、G23F、S24R、S24F、S24W、S24Q、S24H、S24L、G25V、G25F、G25R、V26F、K27L、K27F、K27R、K27V、V28A、V28N、V28E、A29T、V30E、L31F、T33S、T33G、T33D、G34P、I35M、S36T、S36F、S36R、T38L、T38F、T38R、P40N、P40L、P40T、P40W、P40H、P40R、L42I、N43A、N43F、N43I、N43S、N43R、N43M、N43W、N43D、R45T、G46R、A48R、F50C、V51W、V51F、V51H、P52F、P52E、P52N、P55Y、T57R、Q59A、Q59F、Q59R、D60P、D60Q、D60A、N62E、N62Q、G63V、G63M、G63T、G63I、G63A、G63S、G63H、G63Q、G63D、G63E、G63P、H64F、H64T、V68A、V68C、A69N、A69T、A69P、A69W、T71G、T71G、I72C、A74C、L75A、L75F、L75E、L75R、N76D、S78R、S78N、S78I、S78R、I79W、I79Q、V81R、L82F、L82T、L82V、L82R、L82M、A85M、P86W、P86L、P86I、E89P、E89T、E89G、E89H、E89W、E89L、E89V、E89W、E89F、E89I、Y91N、Y91F、A92F、K94N、S99F、S99T、S99P、S99G、S99M、G100S、G100N、G100Q、G100I、S101A、S101N、S101G、S101D、S101T、S101D、S101E、S101P、S101F、G102A、G102T、G102N、G102H、G102E、S103G、S103N、S103D、S103A、V104L、V104I、V104E、V104D、S105T、S105E、S105Q、S106G、S106T、S106E、S106D、S106A、S106V、S106F、I107M、I107F、A108I、A108G、Q109M、L111V、L111I、E112V、E112L、E112Q、A114G、G115K、G115R、N116K、N116A、N116L、N117F、G118R、G118I、M119C、H120A、H120F、H120R、V121F、V121F、V121E、N123G、N123E、L124S、S128D、S128F、S128L、S128N、S128H、S128M、S128I、S128Q、P129E、S132A、S132E、A138G、S144R、V147L、L148I、A158E、G159D、G159E、G159C、S160D、S166D、S166E、Y167W、M175V、V177C、D181A、Q182R、N183I、N183D、N183M、N183R、N183F、N183R、N185E、N185V、N185I、R186H、R186K、S188E、S188D、S188R、Y192H、Y192W、A194E、A194V、A194F、D197F、D197F、I198L、I198F、V203E、V203C、T208S、Y209S、Y209N、Y209F、Y209T、Y209E、Y209H、Y209G、Y209L、P210R、P210V、P210L、G211Q、G211R、S212I、S212M、S212F、T213A、Y214F、A215N、A215D、A215E、A215H、A215F、S216F、S216A、L217E、L217N、L217D、N218D、N218P、N218E、T224A、T224G、V227I、A230E、A231I、A231C、A232V、L233C、V234F、K235F、Q236F、Q236N、Q236H、N238R、N238K、N238L、P239K、P239G、P239R、P239R、P239H、P239T、P239N、P239S、P239F、S240R、W241R、S242L、S242R、N243F、N2
43R、V244R、Q245R、I246S、N248D、N248V、N248I、N248R、H249R、H249T、L250I、K251R、K251S、N252I、N252F、N252R、N252K、N252H、T253I、T253R、T253F、A254C、S256N、G258R、T260V、T260I、L262D、L262H、Y263F、S265F、L267V、L267N、L267M、N269I、N269R、A270C、E271I、E271H、E271V、E271H、E271M、E271L、E271P、E271A、E271F、E271T、A272F、A272F、A272R、A273F、A273I、及びT274Gから選択されるアミノ酸置換の組み合わせを含むアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされる、サブチリシン変異体。 - バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、前記バチルス・レンタスのサブチリシンGG36プロテアーゼが、配列番号2で示されるアミノ酸配列からなり、かつ前記プロテアーゼ変異体は、配列番号2のアミノ酸配列とは、アミノ酸位置1、2、3、4、8、9、10、12、14、15、16、17、18、20、22、23、24、25、26、27、28、29、30、31、33、34、35、36、38、40、42、43、45、46、48、50、51、52、55、57、59、60、62、63、64、68、69、71、72、74、75、76、78、79、81、82、85、86、89、91、92、94、99、100、101、102、103、104、105、106、107、108、109、111、112、114、115、116、117、118、119、120、121、123、124、128、129、132、138、44、147、148、158、159、160、166、167、175、177、181、182、183、185、186、188、192、194、197、198、203、208、209、210、211、212、213、214、215、216、217、218、224、227、230、231、233、234、235、236、236、238、238、239、240、241、242、243、244、246、248、249、250、251、252、253、254、256、258、260、262、263、265、267、269、270、271、272、273、及び274から選択されるアミノ酸位置での2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、前記サブチリシン変異体のアミノ酸位置が、配列番号1で示されるB.アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と対応させて番号付けされ、前記プロテアーゼ変異体のアミノ酸位置が、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。
- バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、前記バチルス・レンタスのサブチリシンGG36プロテアーゼが、配列番号2で示されるアミノ酸配列からなり、かつ前記プロテアーゼ変異体は、配列番号2のアミノ酸配列とは、A1R、Q2S、Q2M、Q2A、Q2R、Q2W、S3R、V4R、V4S、V4C、I8A、S9A、S9F、S9W、R10S、R10A、R10H、R10M、Q12F、Q12R、P14K、P14F、P14Q、A15R、A15F、A16S、H17R、H17M、H17F、N18R、N18K、G20F、G20K、G20R、T22A、T22R、T22Y、T22V、T22Q、T22L、T22W、G23A、G23S、G23F、S24R、S24F、S24W、S24Q、S24H、S24L、G25V、G25F、G25R、V26F、K27L、K27F、K27R、K27V、V28A、V28N、V28E、A29T、V30E、L31F、T33S、T33G、T33D、G34P、I35M、S36T、S36F、S36R、T38L、T38F、T38R、P40N、P40L、P40T、P40W、P40H、P40R、L42I、N43A、N43F、N43I、N43S、N43R、N43M、N43W、N43D、R45T、G46R、A48R、F50C、V51W、V51F、V51H、P52F、P52E、P52N、P55Y、T57R、Q59A、Q59F、Q59R、D60P、D60Q、D60A、N62E、N62Q、G63V、G63M、G63T、G63I、G63A、G63S、G63H、G63Q、G63D、G63E、G63P、H64F、H64T、V68A、V68C、A69N、A69T、A69P、A69W、T71G、T71G、I72C、A74C、L75A、L75F、L75E、L75R、N76D、S78R、S78N、S78I、S78R、I79W、I79Q、V81R、L82F、L82T、L82V、L82R、L82M、A85M、P86W、P86L、P86I、E89P、E89T、E89G、E89H、E89W、E89L、E89V、E89W、E89F、E89I、Y91N、Y91F、A92F、K94N、S99F、S99T、S99P、S99G、S99M、G100S、G100N、G100Q、G100I、S101A、S101N、S101G、S101D、S101T、S101D、S101E、S101P、S101F、G102A、G102T、G102N、G102H、G102E、S103G、S103N、S103D、S103A、V104L、V104I、V104E、V104D、S105T、S105E、S105Q、S106G、S106T、S106E、S106D、S106A、S106V、S106F、I107M、I107F、A108I、A108G、Q109M、L111V、L111I、E112V、E112L、E112Q、A114G、G115K、G115R、N116K、N116A、N116L、N117F、G118R、G118I、M119C、H120A、H120F、H120R、V121F、V121F、V121E、N123G、N123E、L124S、S128D、S128F、S128L、S128N、S128H、S128M、S128I、S128Q、P129E、S132A、S132E、A138G、S144R、V147L、L148I、A158E、G159D、G159E、G159C、S160D、S166D、S166E、Y167W、M175V、V177C、D181A、Q182R、N183I、N183D、N183M、N183R、N183F、N183R、N185E、N185V、N185I、R186H、R186K、S188E、S188D、S188R、Y192H、Y192W、A194E、A194V、A194F、D197F、D197F、I198L、I198F、V203E、V203C、T208S、Y209S、Y209N、Y209F、Y209T、Y209E、Y209H、Y209G、Y209L、P210R、P210V、P210L、G211Q、G211R、S212I、S212M、S212F、T213A、Y214F、A215N、A215D、A215E、A215H、A215F、S216F、S216A、L217E、L217N、L217D、N218D、N218P、N218E、T224A、T224G、V227I、A230E、A231I、A231C、A232V、L233C、V234F、K235F、Q236F、Q236N、Q236H、N238R、N238K、N238L、P239K、P239G、P239R、P239R、P239H、P239T、P239N、P239S、P239F、S240R、W241R、S242L、S242R、N243F、N243R、V244R、Q245R、I246S、N248D、N248V、N248I、N248R、H249R、H249T、L250I、K251R、K251S、N252I、N252F、N252R、N252K、N252H、T253I、T253R、T253F、A254C、S256N、G258R、T260V、T260I、L262D、L262H、Y263F、S265F、L267V、L267N、L267M、N269I、N269R、A270C、E271I、E271H、E271V、E271H、E271M、E271L、E271P、E271A、E271F、E271T、A272F、A272F、A272R、A273F、A273I、及びT274Gからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、前記プロテアーゼ変異体のアミノ酸位置が、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。
- バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、前記バチルス・レンタスのサブチリシンGG36プロテアーゼが配列番号2で示されるアミノ酸配列からなり、前記プロテアーゼ変異体は、配列番号2のアミノ酸配列とは、A1R、Q2S、V4R、V4S、S9A、R10S、P14K、A16S、H17R、N18R、G20R、T22A、T22R、S24R、S24W、G25R、G25V、V26F、L42I、N43R、N43A、G46R、P52F、P52E、P52N、T57R、Q59A、N62E、N62Q、V68A、V68C、T71G、I72C、A74C、L75A、L75F、L75R、N76D、S78R、L82R、P86W、E89P、E89T、E89G、E89H、E89I、E89V、E89W、Y91N、K94N、G100S、S101A、S101N、S101G、S101D、S103G、S103N、V104L、V104I、S106V、S106G、A108I、L111V、E112V、G115K、G115R、N117F、G118I、V121F、S128D、S128F、S128L、S128N、P129E、S144R、L148I、A158E、G159E、S160D、S166D、N185E、N185I、R186H、S188E、S188D、D197F、V203E、Y209S、Y209N、Y209F、Y209T、Y209E、Y209H、Y209G、P210R、S212I、S212F、Y214F、A215N、A215D、A215E、L217E、L217N、T224A、A230E、A231I、Q236F、N238R、N238K、P239K、P239G、P239R、P239S、W241R、S242R、S242L、N243R、V244R、N248I、N248V、H249R、L250I、N252R、T253R、L262D、Y263F、S265F、L267V、L267N、N269I、N269R、E271F、E271I、E271H、E271P、E271T、E271V、E271L及びA272Fからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により
異なるアミノ酸配列からなり、かつ任意選択で、S103A、G159D、Q236H、Q245R、N248D及びN252Kからなる群から選択される少なくとも1つの変異を含み、前記プロテアーゼ変異体のアミノ酸位置は、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。 - バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、前記バチルス・レンタスのサブチリシンGG36プロテアーゼが配列番号2で示されるアミノ酸配列からなり、前記プロテアーゼ変異体が、配列番号2のアミノ酸配列とは、G20K、G20R、G23A、S24F、S24R、N43R、N43W、R45T、N62E、N76D、S101A、N116A、N116L、G118R、S128I、P129E、S188D、T213A、A215F、L217E、P239G、及びN269Rからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、前記プロテアーゼ変異体のアミノ酸位置は、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。
- バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、前記バチルス・レンタスのサブチリシンGG36プロテアーゼが配列番号2で示されるアミノ酸配列からなり、前記プロテアーゼ変異体が、配列番号2のアミノ酸配列とは、A16S、T22A、S24R、N62E、N76D、E89P、S101A/G、S103G/A、V104L/I、L111V、S128N、P129E、A232V、L148I、A158E、G159D/E、R186H、S188D、Y209E、Q236H、Q245R、N248D/R、H249R、N252K/R、T253R、及びE271Fからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記プロテアーゼ変異体のアミノ酸位置が、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。
- バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、前記バチルス・レンタスのサブチリシンGG36プロテアーゼが配列番号2で示されるアミノ酸配列からなり、前記プロテアーゼ変異体が、配列番号2のアミノ酸配列とは、A1R、A230E、E271L、G115R、G20R、H249R、K235F、K27V/F/L、L75E、L82R、N18R、N269R、N43D、N43R、N76D、R45T、S212F、S242R、S24R、S78R、S9A、T22R、V121E、V244R、V28E、V30E、V4R、及びW241Rからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、前記プロテアーゼ変異体のアミノ酸位置は、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。
- バチルス・レンタスのサブチリシンGG36プロテアーゼのプロテアーゼ変異体であって、バチルス・レンタスのサブチリシンGG36プロテアーゼが配列番号2で示されるアミノ酸配列からなり、プロテアーゼ変異体が、配列番号2のアミノ酸配列とは、A1R、A230E、E271L、G115R、G20R、H249R、K235F、K27V/F/L、L75E、L82R、N18R、N269R、N43D、N43R、N76D、R45T、S212F、S242R、S24R、S78R、S9A、T22R、V121E、V244R、V28E、V30E、V4R、及びW241Rからなる群から選択される2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24又は25箇所以下の変異により異なるアミノ酸配列からなり、かつ任意選択で、S103A、G159D、Q236H、Q245R、N248D及びN252Kからなる群から選択される少なくとも1つの変異を含み、前記プロテアーゼ変異体のアミノ酸位置は、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、プロテアーゼ変異体。
- 前記プロテアーゼ変異体が、配列番号2のアミノ酸配列とは異なるアミノ酸配列からなり、かつ前記プロテアーゼ変異体の合計正味電荷が前記バチルス・レンタスのサブチリシンGG36プロテアーゼの合計正味電荷に対して0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5であり、前記親プロテアーゼがGG36であり、前記プロテアーゼ変異体のアミノ酸位置が、前記プロテアーゼ変異体のアミノ酸配列を配列番号1で示されるバチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列と整列させることで決定される、前記バチルス・アミロリケファシエンスのサブチリシンBPN’のアミノ酸配列の対応するアミノ酸位置に割り振られた番号に従って番号付けされる、請求項1〜26のいずれか一項に記載のプロテアーゼ変異体。
- 前記プロテアーゼ変異体が、次の特性:a)試験方法2による性能指数が、少なくとも1.1、少なくとも1.2、少なくとも1.3、少なくとも1.4、少なくとも1.5、少なくとも1.6、少なくとも1.7、少なくとも1.8、少なくとも1.9、少なくとも2、1.1〜約10、1.1〜約8、又は更には1.1〜約5である;b)試験方法3による性能指数が、少なくとも1.1、少なくとも1.2、少なくとも1.3、少なくとも1.4、少なくとも1.5、少なくとも1.6、少なくとも1.7、少なくとも1.8、少なくとも1.9、少なくとも2、1.1〜約10、1.1〜約8、又は更には1.1〜約5である;c)試験方法4による性能指数が、少なくとも1.0、少なくとも1.1、少なくとも1.2、少なくとも1.3、少なくとも1.4、少なくとも1.5、少なくとも1.6、少なくとも1.7、少なくとも1.8、少なくとも1.9、少なくとも2、1.0〜約10、1.0〜約8、又は更には1.0〜約5である;及び/あるいはd)試験方法6による性能指数が、少なくとも1.0、少なくとも1.1、少なくとも1.2、少なくとも1.3、少なくとも1.4、少なくとも1.5、少なくとも1.6、少なくとも1.7、少なくとも1.8、少なくとも1.9、少なくとも2、1.0〜約10、1.0〜約8、又は更には1.0〜約5である、のうちの1つ以上を有する、請求項1〜89のいずれか一項に記載のプロテアーゼ変異体。
- 請求項1〜90のいずれか一項に記載のサブチリシン変異体をコードするポリヌクレオチド配列からなる、単離された核酸。
- 請求項91に記載の核酸を含む、発現ベクター。
- 請求項92に記載の発現ベクターを含む、宿主細胞。
- バチルスサブチリシンの少なくとも1種のサブチリシン変異体を生産する方法であって、 a)請求項1〜90のいずれか一項に記載のサブチリシン変異体を少なくとも1種コードする少なくとも1種の核酸を含む発現ベクターにより、宿主細胞を形質転換させることで、形質転換された宿主細胞を生産する工程;及び b)前記形質転換された宿主細胞を、少なくとも1種のサブチリシン変異体を生産するのに好適な条件下で培養して、少なくとも1種のサブチリシン変異体を生産する工程、を含む、方法。
- 前記生産されたサブチリシン変異体を回収する工程を更に含む、請求項94に記載の方法。
- 前記少なくとも1種の核酸が制御可能なようにプロモーターに連結されている、請求項92に記載の発現ベクター。
- 前記宿主細胞がバチルス種である、請求項94又は95のいずれか一項に記載の方法。
- 前記バチルス種がB.サブチリスである、請求項97に記載の方法。
- 前記組成物が布地ケア製品及びホームケア製品ではない、請求項1〜90のいずれか一項に記載のサブチリシン変異体を少なくとも1種含む、組成物。
- 前記組成物がクリーニング組成物である、請求項99に記載の組成物。
- 前記クリーニング組成物が、粒状、粉末、固体、バー状、液体、錠剤型、ゲル状又はペースト組成物である、請求項99又は100に記載の組成物。
- 更に漂白剤を少なくとも1種含む、請求項99〜101のいずれか一項に記載の組成物。
- 前記クリーニング組成物がリン酸塩を含まない、請求項99〜102のいずれか一項に記載の組成物。
- 前記クリーニング組成物がリン酸塩を含有する、請求項99〜103のいずれか一項に記載の組成物。
- 少なくとも1種の追加の酵素を更に含む、請求項99〜104のいずれか一項に記載の組成物。
- 前記少なくとも1種の追加の酵素が、ヘミセルラーゼ、セルラーゼ、ペルオキシダーゼ、プロテアーゼ、メタロプロテアーゼ、キシラナーゼ、リパーゼ、ホスホリパーゼ、エステラーゼ、ペルヒドロラーゼ、クチナーゼ、ペクチナーゼ、ペクチン酸リアーゼ、マンナナーゼ、ケラチナーゼ、レダクターゼ、オキシダーゼ、フェノールオキシダーゼ、リポキシゲナーゼ、リグニナーゼ、プルラナーゼ、タンナーゼ、ペントサナーゼ、マラナーゼ、β−グルカナーゼ、アラビノシダーゼ、ヒアルロニダーゼ、コンドロイチナーゼ、ラッカーゼ、及びアミラーゼ、又はこれらの任意の組み合わせから選択される、請求項105に記載の組成物。
- 前記サブチリシン変異体が、冷水用プロテアーゼの変異体ではない、請求項99〜106のいずれか一項に記載の組成物。
- 表面又は物品を、請求項1〜90のいずれか一項に記載のサブチリシン変異体を少なくとも1種含むクリーニング組成物と接触させる工程を含む、クリーニング方法。
- 表面又は物品を、請求項100〜107のいずれか一項に記載のクリーニング組成物と接触させる工程を含む、クリーニング方法。
- 前記表面又は物品をそれぞれ前記クリーニング組成物と接触させた後に、前記表面又は物品をすすぐ工程を更に含む、請求項108〜109のいずれか一項に記載の方法。
- 前記表面又は物品をそれぞれ前記クリーニング組成物と接触させた後に、前記表面
又は物品をすすぐ工程を更に含む、請求項108〜110のいずれか一項に記載の方法。 - 前記表面又は物品をすすぐ工程の後に、前記表面又は物品を乾燥させる工程を更に含む、請求項111に記載の方法。
- 請求項100〜107のいずれか一項に記載のクリーニング組成物、及びクリーニングする必要のある表面又は物品を用意する工程;並びに、前記表面又は物品の表面を洗浄するのに好適な条件下で、前記クリーニング組成物を前記表面又は物品と接触させて、前記表面又は物品を洗浄する工程を含む、表面又は物品のクリーニング方法。
- 前記洗浄した表面又は物品をすすいで前記表面又は物品をすすがれた状態にする工程を更に含む、請求項113に記載の方法。
- 前記すすいだ表面又は物品を乾燥させる工程を更に含む、請求項113又は114に記載の方法。
- 前記サブチリシン変異体が、冷水用プロテアーゼの変異体ではない、請求項108〜115のいずれか一項に記載の組成物。
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Families Citing this family (193)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2363455A1 (en) | 2010-03-01 | 2011-09-07 | The Procter & Gamble Company | Composition comprising co-bleach particle and amylase |
EP2705145B1 (en) | 2011-05-05 | 2020-06-17 | The Procter and Gamble Company | Compositions and methods comprising serine protease variants |
TR201901382T4 (tr) | 2011-05-05 | 2019-02-21 | Danisco Inc | Serin proteaz varyantlarını içeren bileşimler ve yöntemler. |
EP2540824A1 (en) | 2011-06-30 | 2013-01-02 | The Procter & Gamble Company | Cleaning compositions comprising amylase variants reference to a sequence listing |
EP2551335A1 (en) | 2011-07-25 | 2013-01-30 | The Procter & Gamble Company | Enzyme stabilized liquid detergent composition |
US20130123162A1 (en) * | 2011-11-10 | 2013-05-16 | The Procter & Gamble Company | Consumer products |
EP3354728B1 (en) | 2012-12-21 | 2020-04-22 | Danisco US Inc. | Alpha-amylase variants |
WO2014099525A1 (en) | 2012-12-21 | 2014-06-26 | Danisco Us Inc. | Paenibacillus curdlanolyticus amylase, and methods of use, thereof |
ES2676895T5 (es) | 2013-03-11 | 2022-04-27 | Danisco Us Inc | Variantes combinatorias de alfa-amilasa |
JP6367930B2 (ja) | 2013-05-29 | 2018-08-01 | ダニスコ・ユーエス・インク | 新規メタロプロテアーゼ |
EP3004314B1 (en) | 2013-05-29 | 2018-06-20 | Danisco US Inc. | Novel metalloproteases |
JP2016526880A (ja) | 2013-05-29 | 2016-09-08 | ダニスコ・ユーエス・インク | 新規メタロプロテアーゼ |
WO2014194054A1 (en) | 2013-05-29 | 2014-12-04 | Danisco Us Inc. | Novel metalloproteases |
WO2014200657A1 (en) | 2013-06-13 | 2014-12-18 | Danisco Us Inc. | Alpha-amylase from streptomyces xiamenensis |
WO2014200658A1 (en) | 2013-06-13 | 2014-12-18 | Danisco Us Inc. | Alpha-amylase from promicromonospora vindobonensis |
WO2014200656A1 (en) | 2013-06-13 | 2014-12-18 | Danisco Us Inc. | Alpha-amylase from streptomyces umbrinus |
WO2014204596A1 (en) | 2013-06-17 | 2014-12-24 | Danisco Us Inc. | Alpha-amylase from bacillaceae family member |
WO2015050724A1 (en) | 2013-10-03 | 2015-04-09 | Danisco Us Inc. | Alpha-amylases from a subset of exiguobacterium, and methods of use, thereof |
WO2015050723A1 (en) | 2013-10-03 | 2015-04-09 | Danisco Us Inc. | Alpha-amylases from exiguobacterium, and methods of use, thereof |
EP3058055A1 (en) | 2013-10-15 | 2016-08-24 | Danisco US Inc. | Clay granule |
US20160289653A1 (en) | 2013-11-14 | 2016-10-06 | Danisco Us Inc. | Stable Enzymes by Glycation Reduction |
WO2015077126A1 (en) | 2013-11-20 | 2015-05-28 | Danisco Us Inc. | Variant alpha-amylases having reduced susceptibility to protease cleavage, and methods of use, thereof |
DK3080262T3 (da) | 2013-12-13 | 2019-05-06 | Danisco Us Inc | Serinproteaser af bacillus-arter |
EP3910057A1 (en) | 2013-12-13 | 2021-11-17 | Danisco US Inc. | Serine proteases of the bacillus gibsonii-clade |
MX2016007920A (es) | 2013-12-18 | 2016-09-13 | Du Pont | Eteres de poli-alfa-1,3-glucano cationicos. |
WO2015112339A1 (en) | 2014-01-22 | 2015-07-30 | The Procter & Gamble Company | Fabric treatment composition |
WO2015112340A1 (en) | 2014-01-22 | 2015-07-30 | The Procter & Gamble Company | Method of treating textile fabrics |
WO2015112338A1 (en) | 2014-01-22 | 2015-07-30 | The Procter & Gamble Company | Method of treating textile fabrics |
WO2015112341A1 (en) | 2014-01-22 | 2015-07-30 | The Procter & Gamble Company | Fabric treatment composition |
WO2015123323A1 (en) | 2014-02-14 | 2015-08-20 | E. I. Du Pont De Nemours And Company | Poly-alpha-1,3-1,6-glucans for viscosity modification |
MX2016011467A (es) | 2014-03-11 | 2016-11-16 | Du Pont | Poli alfa-1,3-glucano oxidado como mejorador de detergente. |
CN106170546A (zh) | 2014-03-21 | 2016-11-30 | 丹尼斯科美国公司 | 芽孢杆菌属的丝氨酸蛋白酶 |
WO2015195777A1 (en) | 2014-06-19 | 2015-12-23 | E. I. Du Pont De Nemours And Company | Compositions containing one or more poly alpha-1,3-glucan ether compounds |
US9714403B2 (en) | 2014-06-19 | 2017-07-25 | E I Du Pont De Nemours And Company | Compositions containing one or more poly alpha-1,3-glucan ether compounds |
WO2016001450A2 (en) * | 2014-07-04 | 2016-01-07 | Novozymes A/S | Subtilase variants and polynucleotides encoding same |
BR112017000102B1 (pt) | 2014-07-04 | 2023-11-07 | Novozymes A/S | Variantes de subtilase de uma subtilase progenitora, composição detergente, uso da mesma e método para a produção de uma variante de subtilase que tem atividade de protease |
US20170233710A1 (en) | 2014-10-17 | 2017-08-17 | Danisco Us Inc. | Serine proteases of bacillus species |
CN107075534A (zh) | 2014-10-24 | 2017-08-18 | 丹尼斯科美国公司 | 使用三肽基肽酶制备醇的方法 |
CN107148472A (zh) | 2014-10-27 | 2017-09-08 | 丹尼斯科美国公司 | 芽孢杆菌属物种的丝氨酸蛋白酶 |
EP3212662B1 (en) | 2014-10-27 | 2020-04-08 | Danisco US Inc. | Serine proteases |
EP3212782B1 (en) | 2014-10-27 | 2019-04-17 | Danisco US Inc. | Serine proteases |
EP3212783B1 (en) | 2014-10-27 | 2024-06-26 | Danisco US Inc. | Serine proteases |
DK3212781T3 (da) | 2014-10-27 | 2019-12-16 | Danisco Us Inc | Serinproteaser |
JP2018501331A (ja) | 2014-11-17 | 2018-01-18 | ザ プロクター アンド ギャンブル カンパニー | 有益剤送達組成物 |
US10760036B2 (en) | 2014-12-15 | 2020-09-01 | Henkel Ag & Co. Kgaa | Detergent composition comprising subtilase variants |
CA2969241A1 (en) | 2014-12-23 | 2016-06-30 | E.I. Du Pont De Nemours And Company | Enzymatically produced cellulose |
US20160289609A1 (en) | 2015-03-30 | 2016-10-06 | The Procter & Gamble Company | Solid free-flowing particulate laundry detergent composition |
EP3075823A1 (en) | 2015-03-30 | 2016-10-05 | The Procter and Gamble Company | A spray-dried laundry detergent base particle |
EP3075826B1 (en) | 2015-03-30 | 2018-01-31 | The Procter and Gamble Company | Solid free-flowing particulate laundry detergent composition |
EP3075824B1 (en) | 2015-03-30 | 2018-02-21 | The Procter and Gamble Company | Solid free-flowing particulate laundry detergent composition |
EP3075831A1 (en) | 2015-03-30 | 2016-10-05 | The Procter and Gamble Company | Solid free-flowing particulate laundry detergent composition |
PL3075827T3 (pl) | 2015-03-30 | 2018-08-31 | The Procter & Gamble Company | Stała sypka rozdrobniona kompozycja detergentowa do prania |
US20160289600A1 (en) | 2015-03-30 | 2016-10-06 | The Procter & Gamble Company | Solid free-flowing particulate laundry detergent composition |
CN107438658B (zh) | 2015-03-30 | 2020-04-21 | 宝洁公司 | 自由流动的固体颗粒状衣物洗涤剂组合物 |
RU2668718C1 (ru) | 2015-03-30 | 2018-10-02 | Дзе Проктер Энд Гэмбл Компани | Твердая композиция моющего средства для стирки из легкосыпучих частиц |
EP3075834B1 (en) | 2015-04-02 | 2018-02-07 | The Procter and Gamble Company | Solid free-flowing particulate laundry detergent composition |
RU2669797C1 (ru) | 2015-04-02 | 2018-10-16 | Дзе Проктер Энд Гэмбл Компани | Твердая композиция моющего средства для стирки из легкосыпучих частиц |
WO2016161219A1 (en) | 2015-04-02 | 2016-10-06 | The Procter & Gamble Company | Solid free-flowing particulate laundry detergent composition |
ES2682178T3 (es) | 2015-04-29 | 2018-09-19 | The Procter & Gamble Company | Composición detergente |
WO2016176240A1 (en) | 2015-04-29 | 2016-11-03 | The Procter & Gamble Company | Method of treating a fabric |
CN107548415A (zh) | 2015-04-29 | 2018-01-05 | 宝洁公司 | 洗涤织物的方法 |
JP6545822B2 (ja) | 2015-04-29 | 2019-07-17 | ザ プロクター アンド ギャンブル カンパニーThe Procter & Gamble Company | 布地の処理方法 |
DK3088503T3 (en) | 2015-04-29 | 2018-08-20 | Procter & Gamble | PROCEDURE FOR TREATING A TEXTILE SUBSTANCE |
EP3872174B1 (en) | 2015-05-13 | 2023-03-01 | Danisco US Inc. | Aprl-clade protease variants and uses thereof |
WO2016201040A1 (en) | 2015-06-09 | 2016-12-15 | Danisco Us Inc. | Water-triggered enzyme suspension |
DK3307427T3 (da) | 2015-06-09 | 2023-11-06 | Danisco Us Inc | Osmotisk sprængnings-kapsler |
WO2016201069A1 (en) | 2015-06-09 | 2016-12-15 | Danisco Us Inc | Low-density enzyme-containing particles |
JP7015695B2 (ja) | 2015-06-17 | 2022-02-03 | ダニスコ・ユーエス・インク | バチルス・ギブソニイ(Bacillus gibsonii)クレードセリンプロテアーゼ |
EP3153426B1 (en) | 2015-10-06 | 2018-07-18 | The Procter & Gamble Company | Flexible box bag comprising soluble unit dose detergent pouch |
EP3153425B1 (en) | 2015-10-06 | 2018-07-04 | The Procter and Gamble Company | Flexible box bag comprising detergent powder and a scoop |
US20180320158A1 (en) | 2015-11-05 | 2018-11-08 | Danisco Us Inc. | Paenibacillus and bacillus spp. mannanases |
EP4141113A1 (en) | 2015-11-05 | 2023-03-01 | Danisco US Inc | Paenibacillus sp. mannanases |
US10183087B2 (en) * | 2015-11-10 | 2019-01-22 | American Sterilizer Company | Cleaning and disinfecting composition |
EP3374488B1 (en) | 2015-11-13 | 2020-10-14 | DuPont Industrial Biosciences USA, LLC | Glucan fiber compositions for use in laundry care and fabric care |
WO2017083228A1 (en) | 2015-11-13 | 2017-05-18 | E. I. Du Pont De Nemours And Company | Glucan fiber compositions for use in laundry care and fabric care |
EP3374401B1 (en) | 2015-11-13 | 2022-04-06 | Nutrition & Biosciences USA 4, Inc. | Glucan fiber compositions for use in laundry care and fabric care |
US10731111B2 (en) | 2015-11-25 | 2020-08-04 | Conopco, Inc. | Liquid laundry detergent composition |
MX2018006475A (es) | 2015-11-26 | 2018-09-28 | Procter & Gamble | Composiciones detergentes liquidas que comprenden proteasa y lipasa encapsulada. |
CN108779448B (zh) | 2015-12-09 | 2023-08-18 | 丹尼斯科美国公司 | α-淀粉酶组合变体 |
US20180362946A1 (en) | 2015-12-18 | 2018-12-20 | Danisco Us Inc. | Polypeptides with endoglucanase activity and uses thereof |
WO2017173190A2 (en) | 2016-04-01 | 2017-10-05 | Danisco Us Inc. | Alpha-amylases, compositions & methods |
WO2017173324A2 (en) | 2016-04-01 | 2017-10-05 | Danisco Us Inc. | Alpha-amylases, compositions & methods |
US20170321157A1 (en) * | 2016-05-03 | 2017-11-09 | The Procter & Gamble Company | Automatic dishwashing detergent composition |
CA3022875A1 (en) | 2016-05-03 | 2017-11-09 | Danisco Us Inc | Protease variants and uses thereof |
EP3845642B1 (en) | 2016-05-05 | 2023-08-09 | Danisco US Inc. | Protease variants and uses thereof |
EP3540036B1 (en) | 2016-05-09 | 2020-11-18 | The Procter & Gamble Company | Detergent composition comprising a fatty acid lipoxygenase |
EP3556834B1 (en) | 2016-05-09 | 2020-10-14 | The Procter & Gamble Company | Detergent composition comprising a fatty acid decarboxylase |
ES2721224T3 (es) | 2016-05-09 | 2019-07-29 | Procter & Gamble | Composición detergente que comprende una enzima transformadora de ácido oleico |
JP2019523645A (ja) | 2016-05-31 | 2019-08-29 | ダニスコ・ユーエス・インク | プロテアーゼ変異体およびその使用 |
JP7152319B2 (ja) | 2016-06-17 | 2022-10-12 | ダニスコ・ユーエス・インク | プロテアーゼ変異体およびその使用 |
EP3269729B1 (en) | 2016-07-14 | 2019-08-21 | The Procter and Gamble Company | Detergent composition |
EP3301155A1 (en) | 2016-10-03 | 2018-04-04 | The Procter & Gamble Company | Laundry detergent composition |
RU2715886C1 (ru) | 2016-10-03 | 2020-03-04 | Дзе Проктер Энд Гэмбл Компани | Композиция моющего средства для стирки с низким показателем ph |
PL3301157T3 (pl) | 2016-10-03 | 2020-09-07 | The Procter & Gamble Company | Kompozycja detergentu piorącego o niskim ph |
CN109715774B (zh) | 2016-10-03 | 2021-10-01 | 宝洁公司 | 低pH衣物洗涤剂组合物 |
RU2709518C1 (ru) | 2016-10-03 | 2019-12-18 | Дзе Проктер Энд Гэмбл Компани | Композиция моющего средства для стирки с низким показателем ph |
RU2716130C9 (ru) | 2016-10-03 | 2020-05-21 | Дзе Проктер Энд Гэмбл Компани | Композиция моющего средства для стирки |
HUE046500T2 (hu) | 2016-10-03 | 2020-02-28 | Procter & Gamble | Mosószerkészítmény |
US20180094220A1 (en) | 2016-10-03 | 2018-04-05 | The Procter & Gamble Company | Laundry detergent composition |
PL3301152T3 (pl) | 2016-10-03 | 2022-06-13 | The Procter & Gamble Company | Suszona rozpyłowo cząstka detergentu nadająca niskie ph w kąpieli piorącej |
WO2018085524A2 (en) | 2016-11-07 | 2018-05-11 | Danisco Us Inc | Laundry detergent composition |
MX2019006421A (es) | 2016-12-02 | 2019-08-01 | Procter & Gamble | Composiciones de limpieza que incluyen enzimas. |
WO2018102479A1 (en) | 2016-12-02 | 2018-06-07 | The Procter & Gamble Company | Cleaning compositions including enzymes |
US10550443B2 (en) | 2016-12-02 | 2020-02-04 | The Procter & Gamble Company | Cleaning compositions including enzymes |
CN110312794B (zh) | 2016-12-21 | 2024-04-12 | 丹尼斯科美国公司 | 吉氏芽孢杆菌进化枝丝氨酸蛋白酶 |
CN110312795A (zh) | 2016-12-21 | 2019-10-08 | 丹尼斯科美国公司 | 蛋白酶变体及其用途 |
EP3339417A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339415A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339422B1 (en) | 2016-12-22 | 2020-10-21 | The Procter & Gamble Company | Laundry detergent composition |
EP3339407A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339419A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339414A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339421A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339416A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339418A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
EP3339413A1 (en) | 2016-12-22 | 2018-06-27 | The Procter & Gamble Company | Laundry detergent composition |
JP2018104705A (ja) * | 2016-12-27 | 2018-07-05 | 花王株式会社 | 繊維製品用粉末洗浄剤組成物 |
CA3051426C (en) | 2017-02-01 | 2023-10-17 | The Procter & Gamble Company | Cleaning compositions comprising amylase variants |
EP3583210B1 (en) * | 2017-03-15 | 2021-07-07 | Danisco US Inc. | Trypsin-like serine proteases and uses thereof |
US20200040283A1 (en) | 2017-03-31 | 2020-02-06 | Danisco Us Inc | Delayed release enzyme formulations for bleach-containing detergents |
WO2018184004A1 (en) | 2017-03-31 | 2018-10-04 | Danisco Us Inc | Alpha-amylase combinatorial variants |
JP2020527339A (ja) | 2017-06-30 | 2020-09-10 | ダニスコ・ユーエス・インク | 低凝集の酵素含有粒子 |
CN111212906B (zh) | 2017-08-18 | 2024-02-02 | 丹尼斯科美国公司 | α-淀粉酶变体 |
CN111373039A (zh) | 2017-11-29 | 2020-07-03 | 丹尼斯科美国公司 | 具有改善的稳定性的枯草杆菌蛋白酶变体 |
US20210222148A1 (en) | 2017-12-21 | 2021-07-22 | Danisco Us Inc. | Enzyme-containing, hot-melt granules comprising a thermotolerant desiccant |
BR112020016068A2 (pt) | 2018-02-08 | 2020-12-08 | Danisco Us Inc. | Partículas cera termicamente resistente matriz para encapsulamento de enzima |
CN108334745B (zh) * | 2018-03-19 | 2022-02-08 | 青岛理工大学 | 一种聚合酶链反应过程非线性混杂系统建模方法 |
EP3546556B1 (en) | 2018-03-28 | 2021-03-10 | The Procter & Gamble Company | Process for preparing a spray-dried laundry detergent particle |
EP3546557B1 (en) | 2018-03-28 | 2020-10-07 | The Procter & Gamble Company | Catalase inhibition during a laundering process |
EP3546555A1 (en) | 2018-03-28 | 2019-10-02 | The Procter & Gamble Company | Process for preparing a spray-dried laundry detergent particle |
EP3546554A1 (en) | 2018-03-28 | 2019-10-02 | The Procter & Gamble Company | Spray-drying process |
EP3546559A1 (en) | 2018-03-28 | 2019-10-02 | The Procter & Gamble Company | Laundry detergent composition |
WO2019191171A1 (en) | 2018-03-28 | 2019-10-03 | The Procter & Gamble Company | Laundry detergent composition |
EP3546558A1 (en) | 2018-03-28 | 2019-10-02 | The Procter & Gamble Company | Laundry detergent composition |
US20210363470A1 (en) | 2018-06-19 | 2021-11-25 | Danisco Us Inc | Subtilisin variants |
US20210214703A1 (en) | 2018-06-19 | 2021-07-15 | Danisco Us Inc | Subtilisin variants |
CA3207822A1 (en) | 2018-06-20 | 2019-12-26 | The Procter & Gamble Company | A fabric care or home care product comprising polysaccharide derivatives |
EP3594319B1 (en) | 2018-07-12 | 2021-05-05 | The Procter & Gamble Company | A solid free-flowing particulate laundry detergent composition |
US20230174962A1 (en) | 2018-07-31 | 2023-06-08 | Danisco Us Inc | Variant alpha-amylases having amino acid substitutions that lower the pka of the general acid |
EP3844255A1 (en) | 2018-08-30 | 2021-07-07 | Danisco US Inc. | Enzyme-containing granules |
US20220033737A1 (en) | 2018-09-27 | 2022-02-03 | Danisco Us Inc | Compositions for medical instrument cleaning |
CN113166745A (zh) | 2018-10-12 | 2021-07-23 | 丹尼斯科美国公司 | 在螯合剂存在下具有可增强稳定性的突变的α-淀粉酶 |
WO2020112599A1 (en) | 2018-11-28 | 2020-06-04 | Danisco Us Inc | Subtilisin variants having improved stability |
US20220056379A1 (en) * | 2018-12-03 | 2022-02-24 | Novozymes A/S | Powder Detergent Compositions |
US11312922B2 (en) | 2019-04-12 | 2022-04-26 | Ecolab Usa Inc. | Antimicrobial multi-purpose cleaner comprising a sulfonic acid-containing surfactant and methods of making and using the same |
WO2020222996A1 (en) | 2019-04-29 | 2020-11-05 | The Procter & Gamble Company | A process for making a laundry detergent composition |
WO2020242858A1 (en) | 2019-05-24 | 2020-12-03 | Danisco Us Inc | Subtilisin variants and methods of use |
CN114174486A (zh) | 2019-06-06 | 2022-03-11 | 丹尼斯科美国公司 | 用于清洁的方法和组合物 |
EP3754010A1 (en) | 2019-06-17 | 2020-12-23 | The Procter & Gamble Company | A solid free-flowing particulate laundry detergent composition comprises a detersive surfactant and a linear polyamine salt |
CN114040972A (zh) | 2019-06-24 | 2022-02-11 | 宝洁公司 | 包含淀粉酶变体的清洁组合物 |
US11492571B2 (en) * | 2019-10-24 | 2022-11-08 | The Procter & Gamble Company | Automatic dishwashing detergent composition comprising a protease |
WO2021080948A2 (en) | 2019-10-24 | 2021-04-29 | Danisco Us Inc | Variant maltopentaose/maltohexaose-forming alpha-amylases |
HUE062018T2 (hu) | 2020-07-06 | 2023-09-28 | Procter & Gamble | Eljárás szemcsés mosószerkészítmény elõállítására |
EP4204553A1 (en) | 2020-08-27 | 2023-07-05 | Danisco US Inc. | Enzymes and enzyme compositions for cleaning |
EP4225883A1 (en) | 2020-10-09 | 2023-08-16 | The Procter & Gamble Company | Packaged laundry detergent product |
CN112745993B (zh) * | 2020-12-28 | 2022-06-24 | 厦门琥珀日化科技股份有限公司 | 一种微胶囊香精及其制备方法和应用 |
CN116997642A (zh) | 2021-01-29 | 2023-11-03 | 丹尼斯科美国公司 | 清洁组合物及其相关的方法 |
CN116897160A (zh) | 2021-02-22 | 2023-10-17 | 丹尼斯科美国公司 | 在色素缺陷型芽孢杆菌属细胞中产生目的蛋白的方法和组合物 |
EP4108754A1 (en) | 2021-06-25 | 2022-12-28 | The Procter & Gamble Company | A process for making a packaged laundry detergent powder |
EP4108756A1 (en) | 2021-06-25 | 2022-12-28 | The Procter & Gamble Company | A laundry detergent powder |
WO2023278297A1 (en) | 2021-06-30 | 2023-01-05 | Danisco Us Inc | Variant lipases and uses thereof |
PL4123005T3 (pl) | 2021-07-19 | 2024-05-20 | The Procter & Gamble Company | Kompozycja czyszcząca zawierająca spory bakteryjne |
WO2023034486A2 (en) | 2021-09-03 | 2023-03-09 | Danisco Us Inc. | Laundry compositions for cleaning |
WO2023039270A2 (en) | 2021-09-13 | 2023-03-16 | Danisco Us Inc. | Bioactive-containing granules |
WO2023114932A2 (en) | 2021-12-16 | 2023-06-22 | Danisco Us Inc. | Subtilisin variants and methods of use |
WO2023114939A2 (en) | 2021-12-16 | 2023-06-22 | Danisco Us Inc. | Subtilisin variants and methods of use |
CA3241094A1 (en) | 2021-12-16 | 2023-06-22 | Jonathan LASSILA | Variant maltopentaose/maltohexaose-forming alpha-amylases |
WO2023114936A2 (en) | 2021-12-16 | 2023-06-22 | Danisco Us Inc. | Subtilisin variants and methods of use |
EP4212608A1 (en) | 2022-01-14 | 2023-07-19 | The Procter & Gamble Company | A method of making a spray-dried laundry detergent particle |
WO2023150905A1 (en) | 2022-02-08 | 2023-08-17 | The Procter & Gamble Company | A method of laundering fabric |
CN118159633A (zh) | 2022-02-08 | 2024-06-07 | 宝洁公司 | 洗涤织物的方法 |
EP4234666A1 (en) | 2022-02-24 | 2023-08-30 | The Procter & Gamble Company | Water-soluble unit dose article comprising a fibrous non-woven sheet and a surfactant system |
EP4234672A1 (en) | 2022-02-24 | 2023-08-30 | The Procter & Gamble Company | Water-soluble unit dose article comprising a fibrous non-woven sheet and a hueing dye particle |
WO2023168234A1 (en) | 2022-03-01 | 2023-09-07 | Danisco Us Inc. | Enzymes and enzyme compositions for cleaning |
WO2023225459A2 (en) | 2022-05-14 | 2023-11-23 | Novozymes A/S | Compositions and methods for preventing, treating, supressing and/or eliminating phytopathogenic infestations and infections |
EP4279570A1 (en) | 2022-05-19 | 2023-11-22 | The Procter & Gamble Company | A process for making a particulate laundry detergent composition |
WO2023250301A1 (en) | 2022-06-21 | 2023-12-28 | Danisco Us Inc. | Methods and compositions for cleaning comprising a polypeptide having thermolysin activity |
EP4299702A1 (en) | 2022-06-27 | 2024-01-03 | The Procter & Gamble Company | A solid free-flowing particulate laundry detergent composition |
EP4299701A1 (en) | 2022-06-27 | 2024-01-03 | The Procter & Gamble Company | A solid free-flowing particulate laundry detergent composition |
EP4299703A1 (en) | 2022-06-27 | 2024-01-03 | The Procter & Gamble Company | A solid free-flowing particulate laundry detergent composition |
EP4299704A1 (en) | 2022-06-27 | 2024-01-03 | The Procter & Gamble Company | A method of laundering and drying fabric |
CN116286565B (zh) * | 2022-07-12 | 2024-06-11 | 湖北佶凯星生物科技有限公司 | 一株高产碱性蛋白酶的枯草芽孢杆菌菌株及其应用 |
WO2024050343A1 (en) | 2022-09-02 | 2024-03-07 | Danisco Us Inc. | Subtilisin variants and methods related thereto |
WO2024050346A1 (en) | 2022-09-02 | 2024-03-07 | Danisco Us Inc. | Detergent compositions and methods related thereto |
WO2024050339A1 (en) | 2022-09-02 | 2024-03-07 | Danisco Us Inc. | Mannanase variants and methods of use |
EP4342969A1 (en) | 2022-09-21 | 2024-03-27 | The Procter & Gamble Company | A solid detergent cleaning composition |
EP4342970A1 (en) | 2022-09-21 | 2024-03-27 | Milliken & Company | Coloured fabric hueing dye agent particles |
EP4364929A1 (en) | 2022-11-01 | 2024-05-08 | The Procter & Gamble Company | Sealing jaws and water-soluble unit dose article comprising a fibrous non-woven sheet |
EP4364930A1 (en) | 2022-11-01 | 2024-05-08 | The Procter & Gamble Company | Sealing jaws and water-soluble unit dose article comprising a fibrous non-woven sheet |
WO2024102698A1 (en) | 2022-11-09 | 2024-05-16 | Danisco Us Inc. | Subtilisin variants and methods of use |
EP4382592A1 (en) | 2022-12-06 | 2024-06-12 | The Procter & Gamble Company | Water-soluble unit dose article comprising a fibrous non-woven sheet and a surfactant system |
EP4389867A1 (en) | 2022-12-23 | 2024-06-26 | The Procter & Gamble Company | A process of making a laundry detergent article |
EP4389866A1 (en) | 2022-12-23 | 2024-06-26 | The Procter & Gamble Company | A process of making a water-soluble detergent unit dose article |
Citations (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04500385A (ja) * | 1989-06-26 | 1992-01-23 | ユニリーバー・ナームローゼ・ベンノートシヤープ | 酵素洗剤組成物 |
JPH04505856A (ja) * | 1989-06-26 | 1992-10-15 | ノボザイムス アクティーゼルスカブ | 突然変異したスブチリシンプロテアーゼ |
JPH07508887A (ja) * | 1992-07-17 | 1995-10-05 | ジェネンコー インターナショナル インコーポレイテッド | 高アルカリ性セリンプロテアーゼ |
JPH09505841A (ja) * | 1993-10-14 | 1997-06-10 | ザ、プロクター、エンド、ギャンブル、カンパニー | プロテアーゼ含有クリーニング組成物 |
JP2005519592A (ja) * | 2002-01-16 | 2005-07-07 | ジェネンコー・インターナショナル・インク | 複数置換プロテアーゼ変異体 |
JP2006505285A (ja) * | 2002-11-06 | 2006-02-16 | ノボザイムス アクティーゼルスカブ | サブチラーゼ変異体 |
WO2009149144A2 (en) * | 2008-06-06 | 2009-12-10 | Danisco Us Inc. | Compositions and methods comprising variant microbial proteases |
WO2010056653A2 (en) * | 2008-11-11 | 2010-05-20 | Danisco Us Inc. | Proteases comprising one or more combinable mutations |
JP2013513385A (ja) * | 2009-12-09 | 2013-04-22 | ダニスコ・ユーエス・インク | プロテアーゼ変異体を含む組成物及び方法 |
JP2013513386A (ja) * | 2009-12-09 | 2013-04-22 | ザ プロクター アンド ギャンブル カンパニー | 布地ケア製品及びホームケア製品 |
JP2013526853A (ja) * | 2010-04-15 | 2013-06-27 | ダニスコ・ユーエス・インク | プロテアーゼ変異体を含む組成物及び方法 |
JP2013527767A (ja) * | 2010-05-06 | 2013-07-04 | ダニスコ・ユーエス・インク | サブチリシン変異体を含む組成物及び方法 |
Family Cites Families (176)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BE680847A (ja) | 1963-05-27 | 1966-11-14 | ||
GB1296839A (ja) | 1969-05-29 | 1972-11-22 | ||
GB1372034A (en) | 1970-12-31 | 1974-10-30 | Unilever Ltd | Detergent compositions |
US4302544A (en) | 1979-10-15 | 1981-11-24 | University Of Rochester | Asporogenous mutant of B. subtilis for use as host component of HV1 system |
DK187280A (da) | 1980-04-30 | 1981-10-31 | Novo Industri As | Ruhedsreducerende middel til et fuldvaskemiddel fuldvaskemiddel og fuldvaskemetode |
GR76237B (ja) | 1981-08-08 | 1984-08-04 | Procter & Gamble | |
US4450235A (en) | 1982-04-21 | 1984-05-22 | Cpc International Inc. | Asporogenic mutant of bacillus subtilis useful as a host in a host-vector system |
US4561998A (en) | 1982-05-24 | 1985-12-31 | The Procter & Gamble Company | Near-neutral pH detergents containing anionic surfactant, cosurfactant and fatty acid |
US4550862A (en) | 1982-11-17 | 1985-11-05 | The Procter & Gamble Company | Liquid product pouring and measuring package with self draining feature |
US4597898A (en) | 1982-12-23 | 1986-07-01 | The Proctor & Gamble Company | Detergent compositions containing ethoxylated amines having clay soil removal/anti-redeposition properties |
US4760025A (en) | 1984-05-29 | 1988-07-26 | Genencor, Inc. | Modified enzymes and methods for making same |
US4515707A (en) | 1983-06-27 | 1985-05-07 | The Chemithon Corporation | Intermediate product for use in producing a detergent bar and method for producing same |
NZ208806A (en) | 1983-07-06 | 1988-07-28 | Gist Brocades Nv | Genetic engineering of industrial microorganism species: readily-transformable host used as intermediate in transfer of dna to the industrial species; plasmids |
US4515705A (en) | 1983-11-14 | 1985-05-07 | The Procter & Gamble Company | Compositions containing odor purified proteolytic enzymes and perfumes |
US4537706A (en) | 1984-05-14 | 1985-08-27 | The Procter & Gamble Company | Liquid detergents containing boric acid to stabilize enzymes |
US5264366A (en) | 1984-05-29 | 1993-11-23 | Genencor, Inc. | Protease deficient bacillus |
US5972682A (en) | 1984-05-29 | 1999-10-26 | Genencor International, Inc. | Enzymatically active modified subtilisins |
US5801038A (en) | 1984-05-29 | 1998-09-01 | Genencor International Inc. | Modified subtilisins having amino acid alterations |
DK171161B1 (da) | 1985-03-28 | 1996-07-08 | Hoffmann La Roche | Fremgangsmåde til påvisning af forekomst eller fravær af mindst én specifik nukleinsyresekvens i en prøve eller til skelnen mellem to forskellige nukleinsyresekvenser i denne prøve |
US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
US4965188A (en) | 1986-08-22 | 1990-10-23 | Cetus Corporation | Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme |
US4683202A (en) | 1985-03-28 | 1987-07-28 | Cetus Corporation | Process for amplifying nucleic acid sequences |
DK154572C (da) | 1985-08-07 | 1989-04-24 | Novo Industri As | Enzymatisk detergentadditiv, detergent og fremgangsmaade til vask af tekstiler |
EP0218272B1 (en) | 1985-08-09 | 1992-03-18 | Gist-Brocades N.V. | Novel lipolytic enzymes and their use in detergent compositions |
US4762636A (en) | 1986-02-28 | 1988-08-09 | Ciba-Geigy Corporation | Process for the preparation of granules containing an active substance and to the use thereof as speckles for treating substrates |
DK122686D0 (da) | 1986-03-17 | 1986-03-17 | Novo Industri As | Fremstilling af proteiner |
JP2503986B2 (ja) | 1986-08-08 | 1996-06-05 | 関西ペイント株式会社 | 無毒性防汚塗料組成物 |
DE3750450T2 (de) | 1986-08-29 | 1995-01-05 | Novo Industri As | Enzymhaltiger Reinigungsmittelzusatz. |
GB8629837D0 (en) | 1986-12-13 | 1987-01-21 | Interox Chemicals Ltd | Bleach activation |
US4765916A (en) | 1987-03-24 | 1988-08-23 | The Clorox Company | Polymer film composition for rinse release of wash additives |
US4972017A (en) | 1987-03-24 | 1990-11-20 | The Clorox Company | Rinse soluble polymer film composition for wash additives |
DE3851875T2 (de) | 1987-05-29 | 1995-04-13 | Genencor Int | Cutinase haltige reinigungsmittelzusammensetzungen. |
ATE125865T1 (de) | 1987-08-28 | 1995-08-15 | Novo Nordisk As | Rekombinante humicola-lipase und verfahren zur herstellung von rekombinanten humicola-lipasen. |
JPS6474992A (en) | 1987-09-16 | 1989-03-20 | Fuji Oil Co Ltd | Dna sequence, plasmid and production of lipase |
US5288627A (en) | 1988-01-07 | 1994-02-22 | Novo Nordisk A/S | Endoprotease from Fusarium oxysporumDSM 2672 for use in detergents |
DE68924654T2 (de) | 1988-01-07 | 1996-04-04 | Novonordisk As | Spezifische Protease. |
CN1056187C (zh) * | 1988-02-11 | 2000-09-06 | 金克克国际有限公司 | 新的蛋白水解酶及其在洗涤剂中的应用 |
JP3079276B2 (ja) | 1988-02-28 | 2000-08-21 | 天野製薬株式会社 | 組換え体dna、それを含むシュードモナス属菌及びそれを用いたリパーゼの製造法 |
US4977252A (en) | 1988-03-11 | 1990-12-11 | National Starch And Chemical Investment Holding Corporation | Modified starch emulsifier characterized by shelf stability |
GB8806016D0 (en) | 1988-03-14 | 1988-04-13 | Danochemo As | Encapsulated photoactivator dyes for detergent use |
US5648263A (en) | 1988-03-24 | 1997-07-15 | Novo Nordisk A/S | Methods for reducing the harshness of a cotton-containing fabric |
DE68911131T2 (de) | 1988-03-24 | 1994-03-31 | Novonordisk As | Cellulosezubereitung. |
US4968451A (en) | 1988-08-26 | 1990-11-06 | The Procter & Gamble Company | Soil release agents having allyl-derived sulfonated end caps |
WO1990009446A1 (en) | 1989-02-17 | 1990-08-23 | Plant Genetic Systems N.V. | Cutinase |
US5665587A (en) * | 1989-06-26 | 1997-09-09 | Novo Nordisk A/S | Modified subtilisins and detergent compositions containing same |
DK0493398T3 (da) | 1989-08-25 | 2000-05-22 | Henkel Research Corp | Alkalisk, proteolytisk enzym og fremgangsmåde til fremstilling deraf |
DE4023458A1 (de) * | 1989-08-31 | 1991-03-07 | Kali Chemie Ag | Neue hochalkalische proteasen |
US5352603A (en) | 1989-08-31 | 1994-10-04 | Kali-Chemie Ag | Highly alkaline proteases |
JP3112937B2 (ja) | 1990-04-14 | 2000-11-27 | カリ―ヒエミー アクチエンゲゼルシヤフト | アルカリ性バチルスーリパーゼ、これをコード化するdna配列およびこのリパーゼを生産するバチルス |
WO1991017243A1 (en) | 1990-05-09 | 1991-11-14 | Novo Nordisk A/S | A cellulase preparation comprising an endoglucanase enzyme |
DK115890D0 (da) | 1990-05-09 | 1990-05-09 | Novo Nordisk As | Enzym |
US5354559A (en) | 1990-05-29 | 1994-10-11 | Grain Processing Corporation | Encapsulation with starch hydrolyzate acid esters |
ES2174820T3 (es) | 1991-01-16 | 2002-11-16 | Procter & Gamble | Composiciones detergentes compactas con celulasa de alta actividad. |
US5520838A (en) | 1991-01-16 | 1996-05-28 | The Procter & Gamble Company | Compact detergent compositions with high activity cellulase |
GB9108136D0 (en) | 1991-04-17 | 1991-06-05 | Unilever Plc | Concentrated detergent powder compositions |
US5340735A (en) | 1991-05-29 | 1994-08-23 | Cognis, Inc. | Bacillus lentus alkaline protease variants with increased stability |
DE69334295D1 (de) | 1992-07-23 | 2009-11-12 | Novo Nordisk As | MUTIERTE -g(a)-AMYLASE, WASCHMITTEL UND GESCHIRRSPÜLMITTEL |
WO1994007998A1 (en) | 1992-10-06 | 1994-04-14 | Novo Nordisk A/S | Cellulase variants |
CA2150562A1 (en) | 1992-12-01 | 1994-06-09 | Palle Schneider | Enhancement of enzyme reactions |
CA2154157C (en) | 1993-01-18 | 1999-08-03 | Fiona Susan Macbeath | Machine dishwashing detergent compositions |
EP0867504B2 (en) | 1993-02-11 | 2011-05-18 | Genencor International, Inc. | Oxidation-stable alpha-amylase |
DE59405259D1 (de) | 1993-05-08 | 1998-03-19 | Henkel Kgaa | Silberkorrosionsschutzmittel i |
HU218021B (hu) | 1993-05-08 | 2000-05-28 | Henkel Kommanditgesellschaft Auf Aktien | Ezüst korróziója ellen védő szerek (II) és ezeket tartalmazó gépitisztítószerek |
DK77393D0 (da) | 1993-06-29 | 1993-06-29 | Novo Nordisk As | Aktivering af enzymer |
US5698504A (en) | 1993-07-01 | 1997-12-16 | The Procter & Gamble Company | Machine dishwashing composition containing oxygen bleach and paraffin oil and benzotriazole compound silver tarnishing inhibitors |
US5486303A (en) | 1993-08-27 | 1996-01-23 | The Procter & Gamble Company | Process for making high density detergent agglomerates using an anhydrous powder additive |
US6436690B1 (en) * | 1993-09-15 | 2002-08-20 | The Procter & Gamble Company | BPN′ variants having decreased adsorption and increased hydrolysis wherein one or more loop regions are substituted |
MA23346A1 (fr) * | 1993-10-14 | 1995-04-01 | Genencor Int | Variantes de la subtilisine |
US5861271A (en) | 1993-12-17 | 1999-01-19 | Fowler; Timothy | Cellulase enzymes and systems for their expressions |
US5691295A (en) | 1995-01-17 | 1997-11-25 | Cognis Gesellschaft Fuer Biotechnologie Mbh | Detergent compositions |
ES2364774T3 (es) | 1994-02-24 | 2011-09-14 | HENKEL AG & CO. KGAA | Enzimas mejoradas y detergentes que las contienen. |
ATE512226T1 (de) | 1994-02-24 | 2011-06-15 | Henkel Ag & Co Kgaa | Verbesserte enzyme und detergentien damit |
US5912157A (en) | 1994-03-08 | 1999-06-15 | Novo Nordisk A/S | Alkaline cellulases |
MX196038B (es) | 1994-03-29 | 2000-04-14 | Novo Nordisk As | Amilasa de bacillus alcalino. |
DE4411223A1 (de) * | 1994-03-31 | 1995-10-05 | Solvay Enzymes Gmbh & Co Kg | Verwendung alkalischer Proteasen in gewerblichen Textilwaschverfahren |
US5686014A (en) | 1994-04-07 | 1997-11-11 | The Procter & Gamble Company | Bleach compositions comprising manganese-containing bleach catalysts |
JP3139277B2 (ja) | 1994-05-10 | 2001-02-26 | 松下電器産業株式会社 | 浄水器及び浄水システム |
PE6995A1 (es) | 1994-05-25 | 1995-03-20 | Procter & Gamble | Composicion que comprende un polimero de polialquilenoamina etoxilado propoxilado como agente de separacion de sucio |
CA2193117C (en) | 1994-06-17 | 2007-10-30 | Roelck Anneke Cuperus | Cleaning compositions containing plant cell wall degrading enzymes and their use in cleaning methods |
GB2294268A (en) | 1994-07-07 | 1996-04-24 | Procter & Gamble | Bleaching composition for dishwasher use |
US5879584A (en) | 1994-09-10 | 1999-03-09 | The Procter & Gamble Company | Process for manufacturing aqueous compositions comprising peracids |
US5691297A (en) | 1994-09-20 | 1997-11-25 | The Procter & Gamble Company | Process for making a high density detergent composition by controlling agglomeration within a dispersion index |
US5516448A (en) | 1994-09-20 | 1996-05-14 | The Procter & Gamble Company | Process for making a high density detergent composition which includes selected recycle streams for improved agglomerate |
US5489392A (en) | 1994-09-20 | 1996-02-06 | The Procter & Gamble Company | Process for making a high density detergent composition in a single mixer/densifier with selected recycle streams for improved agglomerate properties |
AU3604595A (en) | 1994-10-06 | 1996-05-02 | Novo Nordisk A/S | An enzyme and enzyme preparation with endoglucanase activity |
ES2145315T3 (es) | 1994-12-09 | 2000-07-01 | Procter & Gamble | Composicion para lavavajillas automaticos que contiene particulas de peroxidos de diacilo. |
US6440716B1 (en) | 1995-02-03 | 2002-08-27 | Novozymes A/S | α-amylase mutants |
US5534179A (en) | 1995-02-03 | 1996-07-09 | Procter & Gamble | Detergent compositions comprising multiperacid-forming bleach activators |
US6093562A (en) | 1996-02-05 | 2000-07-25 | Novo Nordisk A/S | Amylase variants |
US5574005A (en) | 1995-03-07 | 1996-11-12 | The Procter & Gamble Company | Process for producing detergent agglomerates from high active surfactant pastes having non-linear viscoelastic properties |
CN1182451A (zh) | 1995-03-17 | 1998-05-20 | 诺沃挪第克公司 | 新的内切葡聚糖酶 |
US5569645A (en) | 1995-04-24 | 1996-10-29 | The Procter & Gamble Company | Low dosage detergent composition containing optimum proportions of agglomerates and spray dried granules for improved flow properties |
JP3025627B2 (ja) | 1995-06-14 | 2000-03-27 | 花王株式会社 | 液化型アルカリα−アミラーゼ遺伝子 |
US5597936A (en) | 1995-06-16 | 1997-01-28 | The Procter & Gamble Company | Method for manufacturing cobalt catalysts |
EP0832176B1 (en) | 1995-06-16 | 2001-07-11 | The Procter & Gamble Company | Automatic dishwashing compositions comprising cobalt catalysts |
US5565422A (en) | 1995-06-23 | 1996-10-15 | The Procter & Gamble Company | Process for preparing a free-flowing particulate detergent composition having improved solubility |
DE19530816A1 (de) | 1995-08-23 | 1997-02-27 | Cognis Bio Umwelt | Verwendung von mutierter Subtilisin-Protease in kosmetischen Produkten |
US5576282A (en) | 1995-09-11 | 1996-11-19 | The Procter & Gamble Company | Color-safe bleach boosters, compositions and laundry methods employing same |
JP4121556B2 (ja) | 1995-09-18 | 2008-07-23 | ザ プロクター アンド ギャンブル カンパニー | デリバリーシステム |
MA24137A1 (fr) | 1996-04-16 | 1997-12-31 | Procter & Gamble | Fabrication d'agents de surface ramifies . |
US5763385A (en) | 1996-05-14 | 1998-06-09 | Genencor International, Inc. | Modified α-amylases having altered calcium binding properties |
US6380144B1 (en) | 1996-07-31 | 2002-04-30 | The Procter & Gamble Company | Detergent composition |
US5929022A (en) | 1996-08-01 | 1999-07-27 | The Procter & Gamble Company | Detergent compositions containing amine and specially selected perfumes |
WO1998008940A1 (en) | 1996-08-26 | 1998-03-05 | Novo Nordisk A/S | A novel endoglucanase |
CN100362100C (zh) | 1996-09-17 | 2008-01-16 | 诺沃奇梅兹有限公司 | 纤维素酶变体 |
AU731577B2 (en) | 1997-03-07 | 2001-04-05 | Procter & Gamble Company, The | Bleach compositions containing metal bleach catalyst, and bleach activators and/or organic percarboxylic acids |
US6225464B1 (en) | 1997-03-07 | 2001-05-01 | The Procter & Gamble Company | Methods of making cross-bridged macropolycycles |
US6268197B1 (en) | 1997-07-07 | 2001-07-31 | Novozymes A/S | Xyloglucan-specific alkaline xyloglucanase from bacillus |
GB2327947A (en) | 1997-08-02 | 1999-02-10 | Procter & Gamble | Detergent tablet |
US6376445B1 (en) | 1997-08-14 | 2002-04-23 | Procter & Gamble Company | Detergent compositions comprising a mannanase and a protease |
DE19736591A1 (de) | 1997-08-22 | 1999-02-25 | Peter Prof Dr Hegemann | Verfahren zum Herstellen von Nukleinsäurepolymeren |
ES2322825T3 (es) | 1997-10-13 | 2009-06-29 | Novozymes A/S | Mutantes de alfa-amilasa. |
EP0913458B1 (en) * | 1997-10-22 | 2004-06-16 | The Procter & Gamble Company | Liquid hard-surface cleaning compositions |
AR015977A1 (es) * | 1997-10-23 | 2001-05-30 | Genencor Int | Variantes de proteasa multiplemente substituida con carga neta alterada para su empleo en detergentes |
ES2367505T3 (es) * | 1997-10-23 | 2011-11-04 | Danisco Us Inc. | Variantes de proteasa con sustituciones múltiples con carga neta alterada para usar en detergentes. |
RU2269572C2 (ru) * | 1997-10-23 | 2006-02-10 | Джененкор Интернэшнл, Инк. | Варианты протеазы, замещенные в нескольких положениях |
EP2388267A1 (en) | 1997-10-30 | 2011-11-23 | Novozymes A/S | Alpha-amylase mutants |
US5935826A (en) | 1997-10-31 | 1999-08-10 | National Starch And Chemical Investment Holding Corporation | Glucoamylase converted starch derivatives and their use as emulsifying and encapsulating agents |
US6287839B1 (en) | 1997-11-19 | 2001-09-11 | Genencor International, Inc. | Cellulase producing actinomycetes, cellulase produced therefrom and method of producing same |
KR100762164B1 (ko) | 1997-11-21 | 2007-10-01 | 노보자임스 에이/에스 | 프로테아제 변이체 및 조성물 |
AU2207099A (en) | 1997-12-24 | 1999-07-19 | Genencor International, Inc. | An improved method of assaying for a preferred enzyme and/or preferred detergentcomposition |
GB9807477D0 (en) | 1998-04-07 | 1998-06-10 | Unilever Plc | Coloured granular composition for use in particulate detergent compositions |
DE59910042D1 (de) | 1998-05-18 | 2004-09-02 | Ciba Sc Holding Ag | Wasserlösliche Granulate von Phthalocyaninverbindungen |
WO1999064619A2 (en) | 1998-06-10 | 1999-12-16 | Novozymes A/S | Novel mannanases |
PH11999002188B1 (en) | 1998-09-01 | 2007-08-06 | Unilever Nv | Method of treating a textile |
JP2003512012A (ja) | 1998-10-23 | 2003-04-02 | ザ、プロクター、エンド、ギャンブル、カンパニー | 洗剤組成物に用いられるプロテアーゼ変異体のスクリーニング法 |
US6376450B1 (en) | 1998-10-23 | 2002-04-23 | Chanchal Kumar Ghosh | Cleaning compositions containing multiply-substituted protease variants |
US6294514B1 (en) | 1998-11-24 | 2001-09-25 | The Procter & Gamble Company | Process for preparing mono-long chain amine oxide surfactants with low nitrite, nitrosamine and low residual peroxide |
WO2000032601A2 (en) | 1998-11-30 | 2000-06-08 | The Procter & Gamble Company | Process for preparing cross-bridged tetraaza macrocycles |
US6403355B1 (en) | 1998-12-21 | 2002-06-11 | Kao Corporation | Amylases |
AU3420100A (en) | 1999-03-31 | 2000-10-23 | Novozymes A/S | Lipase variant |
GB9930697D0 (en) | 1999-12-24 | 2000-02-16 | Unilever Plc | Method of treating a textile |
US6815192B2 (en) | 2000-02-24 | 2004-11-09 | Novozymes A/S | Family 44 xyloglucanases |
US6630340B2 (en) | 2000-03-01 | 2003-10-07 | Novozymes A/S | Family 5 xyloglucanases |
KR20030037267A (ko) | 2000-07-28 | 2003-05-12 | 헨켈 코만디트게젤샤프트 아우프 악티엔 | 바실러스속 a 7-7 (dsm 12368) 에서 추출한신규한 아밀분해 효소 및 상기 신규한 아밀분해 효소를함유하는 세척 및 세정제 |
EP1309677B2 (en) | 2000-08-11 | 2012-04-11 | Genencor International, Inc. | Bacillus transformation, transformants and mutant libraries |
US6440991B1 (en) | 2000-10-02 | 2002-08-27 | Wyeth | Ethers of 7-desmethlrapamycin |
US6582914B1 (en) | 2000-10-26 | 2003-06-24 | Genencor International, Inc. | Method for generating a library of oligonucleotides comprising a controlled distribution of mutations |
CN100489094C (zh) * | 2001-03-23 | 2009-05-20 | 金克克国际有限公司 | 具有改变的免疫原性反应的蛋白质及制备和使用该蛋白质的方法 |
AU2002249102A1 (en) | 2001-03-27 | 2002-10-08 | Novozymes A/S | Family 74 xyloglucanases |
US7041488B2 (en) | 2001-06-06 | 2006-05-09 | Novozymes A/S | Endo-beta-1,4-glucanase from bacillus |
GB0114847D0 (en) | 2001-06-18 | 2001-08-08 | Unilever Plc | Water soluble package and liquid contents thereof |
DK200101090A (da) * | 2001-07-12 | 2001-08-16 | Novozymes As | Subtilase variants |
WO2003018740A1 (en) | 2001-08-20 | 2003-03-06 | Unilever Plc | Photobleach speckle and laundry detergent compositions containing it |
GB0120160D0 (en) | 2001-08-20 | 2001-10-10 | Unilever Plc | Photobleach speckle and laundry detergent compositions containing it |
DE10162728A1 (de) | 2001-12-20 | 2003-07-10 | Henkel Kgaa | Neue Alkalische Protease aus Bacillus gibsonii (DSM 14393) und Wasch-und Reinigungsmittel enthaltend diese neue Alkalische Protease |
EP1499629A4 (en) | 2002-04-19 | 2006-03-29 | Novozymes Inc | POLYPEPTIDES WITH XYLOGLUCANASE EFFECT AND NUCLEIC ACIDS CODING THEREOF |
US7557076B2 (en) | 2002-06-06 | 2009-07-07 | The Procter & Gamble Company | Organic catalyst with enhanced enzyme compatibility |
US8080511B2 (en) | 2002-09-04 | 2011-12-20 | Basf Se | Formulations comprising water-soluble granulates |
KR100554479B1 (ko) | 2002-09-11 | 2006-03-03 | 씨제이라이온 주식회사 | 염착 얼룩 방지 세탁용 착염 |
DE10260805A1 (de) | 2002-12-23 | 2004-07-22 | Geneart Gmbh | Verfahren und Vorrichtung zum Optimieren einer Nucleotidsequenz zur Expression eines Proteins |
DE60319347T2 (de) | 2003-05-23 | 2009-02-19 | The Procter & Gamble Company, Cincinnati | Waschmittelzusammensetzung zum Gebrauch in einer Textilwasch- oder Geschirrspülmaschine |
GB0325432D0 (en) | 2003-10-31 | 2003-12-03 | Unilever Plc | Ligand and complex for catalytically bleaching a substrate |
EP1692158B1 (en) | 2003-11-06 | 2011-10-26 | Danisco US Inc. | Vegf binding and supported peptides for treating skin diseases |
US7985569B2 (en) | 2003-11-19 | 2011-07-26 | Danisco Us Inc. | Cellulomonas 69B4 serine protease variants |
DK2292743T3 (da) | 2003-12-03 | 2013-11-25 | Danisco Us Inc | Perhydrolase |
DE102004027091A1 (de) * | 2004-06-02 | 2005-12-29 | Henkel Kgaa | Leistungsverbesserte Alkalische Protease-Varianten und Wasch- und Reinigungsmittel, enthaltend diese leistungsverbesserten Alkalische Protease-Varianten |
US7208459B2 (en) | 2004-06-29 | 2007-04-24 | The Procter & Gamble Company | Laundry detergent compositions with efficient hueing dye |
EP4269684A3 (en) | 2004-07-05 | 2024-02-21 | Novozymes A/S | Alpha-amylase variants with altered properties |
ATE529505T1 (de) * | 2005-07-08 | 2011-11-15 | Novozymes As | Subtilase varianten |
JP2009500515A (ja) * | 2005-07-11 | 2009-01-08 | ジェネンコー・インターナショナル・インク | 消費者用布処理用酵素タブレットとその製法 |
EP1934340B1 (en) | 2005-10-12 | 2014-03-12 | Danisco US Inc. | Use and production of storage-stable neutral metalloprotease |
EP1979456A2 (en) | 2006-01-23 | 2008-10-15 | The Procter & Gamble Company | A composition comprising a lipase and a bleach catalyst |
EP2038394A2 (en) | 2006-06-05 | 2009-03-25 | The Procter & Gamble Company | Enzyme stabilizer |
EP2059591B1 (en) | 2006-07-18 | 2012-09-05 | Danisco US Inc. | Dishwashing composition that contains a protease variant |
US20080221008A1 (en) * | 2006-10-06 | 2008-09-11 | Novozymes A/S | Detergent compositions and the use of enzyme combinations therein |
CN101784662B (zh) * | 2007-06-06 | 2014-11-05 | 丹尼斯科美国公司 | 用于改善蛋白质特性的方法 |
CA2687560C (en) | 2007-06-11 | 2013-05-14 | The Procter & Gamble Company | Benefit agent containing delivery particle |
DE102007038031A1 (de) | 2007-08-10 | 2009-06-04 | Henkel Ag & Co. Kgaa | Mittel enthaltend Proteasen |
DE102007047433A1 (de) * | 2007-10-04 | 2009-04-09 | Lanxess Deutschland Gmbh | Flüssigwasch- und Flüssigreinigungsmittel |
MX2010009457A (es) | 2008-02-29 | 2010-09-24 | Procter & Gamble | Composicion detergente que comprende lipasa. |
EP2100947A1 (en) | 2008-03-14 | 2009-09-16 | The Procter and Gamble Company | Automatic dishwashing detergent composition |
MX2010010468A (es) | 2008-03-26 | 2010-10-20 | Procter & Gamble | Particula de suministro. |
EP2166092A1 (en) * | 2008-09-18 | 2010-03-24 | The Procter and Gamble Company | Detergent composition |
CN104293751B (zh) * | 2008-11-11 | 2018-11-27 | 丹尼斯科美国公司 | 包含丝氨酸蛋白酶变体的组合物和方法 |
RU2011123745A (ru) * | 2008-11-11 | 2012-12-20 | ДАНИСКО ЮЭс ИНК. | Композиции и способы, включающие вариант субтилизина |
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Patent Citations (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH04500385A (ja) * | 1989-06-26 | 1992-01-23 | ユニリーバー・ナームローゼ・ベンノートシヤープ | 酵素洗剤組成物 |
JPH04505856A (ja) * | 1989-06-26 | 1992-10-15 | ノボザイムス アクティーゼルスカブ | 突然変異したスブチリシンプロテアーゼ |
JPH07508887A (ja) * | 1992-07-17 | 1995-10-05 | ジェネンコー インターナショナル インコーポレイテッド | 高アルカリ性セリンプロテアーゼ |
JPH09505841A (ja) * | 1993-10-14 | 1997-06-10 | ザ、プロクター、エンド、ギャンブル、カンパニー | プロテアーゼ含有クリーニング組成物 |
JP2005519592A (ja) * | 2002-01-16 | 2005-07-07 | ジェネンコー・インターナショナル・インク | 複数置換プロテアーゼ変異体 |
JP2006505285A (ja) * | 2002-11-06 | 2006-02-16 | ノボザイムス アクティーゼルスカブ | サブチラーゼ変異体 |
WO2009149144A2 (en) * | 2008-06-06 | 2009-12-10 | Danisco Us Inc. | Compositions and methods comprising variant microbial proteases |
WO2009149200A2 (en) * | 2008-06-06 | 2009-12-10 | Danisco Us Inc. | Compositions and methods comprising variant microbial proteases |
WO2010056653A2 (en) * | 2008-11-11 | 2010-05-20 | Danisco Us Inc. | Proteases comprising one or more combinable mutations |
JP2013513385A (ja) * | 2009-12-09 | 2013-04-22 | ダニスコ・ユーエス・インク | プロテアーゼ変異体を含む組成物及び方法 |
JP2013513386A (ja) * | 2009-12-09 | 2013-04-22 | ザ プロクター アンド ギャンブル カンパニー | 布地ケア製品及びホームケア製品 |
JP2013526853A (ja) * | 2010-04-15 | 2013-06-27 | ダニスコ・ユーエス・インク | プロテアーゼ変異体を含む組成物及び方法 |
JP2013527767A (ja) * | 2010-05-06 | 2013-07-04 | ダニスコ・ユーエス・インク | サブチリシン変異体を含む組成物及び方法 |
JP2015187278A (ja) * | 2010-05-06 | 2015-10-29 | ザ プロクター アンド ギャンブルカンパニー | プロテアーゼ変異体を有する消費者製品 |
JP5813753B2 (ja) * | 2010-05-06 | 2015-11-17 | ザ プロクター アンド ギャンブルカンパニー | プロテアーゼ変異体を有する消費者製品 |
Non-Patent Citations (1)
Title |
---|
TINDBAEK, N. ET AL., PROTEIN ENG. DES. SEL., vol. 17, no. 2, JPN6017012982, 2004, pages 149 - 156, ISSN: 0003642356 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018078904A (ja) * | 2010-05-06 | 2018-05-24 | ダニスコ・ユーエス・インク | サブチリシン変異体を含む組成物及び方法 |
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