JP6367161B2 - セリンプロテアーゼ変異体を含む組成物及び方法 - Google Patents
セリンプロテアーゼ変異体を含む組成物及び方法 Download PDFInfo
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- LKHDXIBHVSGUHN-UHFFFAOYSA-N thiadiazole 1,1-dioxide Chemical compound O=S1(=O)C=CN=N1 LKHDXIBHVSGUHN-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/52—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea
- C12N9/54—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from bacteria or Archaea bacteria being Bacillus
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
- C11D3/38681—Chemically modified or immobilised enzymes
Landscapes
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biotechnology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Detergent Compositions (AREA)
- Enzymes And Modification Thereof (AREA)
- Chemical Or Physical Treatment Of Fibers (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Developing Agents For Electrophotography (AREA)
Description
別途記載のない限り、本発明の調製は、当該技術分野内の分子生物学、タンパク質工学、微生物学及び組み換えDNAにおいて通常使用される従来技術を伴う。このような技術は当業者に既知のものであり、当業者に広く知られている数多くの文献及び参考文献に記載されている。本明細書で引用される全ての特許、特許出願、論文及び刊行物は、参照により明示的に本案件に組み込まれる。
US,Genencor Division);並びにHenkel/Kemiraから市販されているもの、即ちBLAP(米国特許第5,352,604号の図29に示される、変異S99D+S101 R+S103A+V104I+G159Sを有する配列、以降BLAPと呼ぶ)及びBLAP X(S3T+V4I+V205Iを有するBLAP)が挙げられる。
典型的には、対象とする核酸は、対象とするタンパク質を発現する。発現ベクター又は発現カセットは、典型的には外来核酸の発現を駆動又は促進するプロモーターヌクレオチド配列を含む。また、典型的には発現ベクター又はカセットは、標的細胞で特定の核酸を転写させる任意の他の特異的な核酸配列を包含する。組み換え型発現カセットは、プラスミド、染色体、ミトコンドリアDNA、プラスミドDNA、ウイルス、又は核酸断に組み込むことができる。一部の発現ベクターは宿主細胞に異種性のDNA断片を組み込み、発現させすることができる。多くの原核及び真核細胞性発現ベクターは、市販されている。適切な発現ベクターは、当業者の知識の範囲内で選択される。発現ベクターに組み込まれた核酸配列からタンパク質を発現させるのに適切な発現ベクターの選択は、当業者の知識の範囲内のものである。
1993]参照)。特に有用なBLASTプログラムはWU−BLAST−2プログラムである(Altschul et al.,Meth.Enzymol.266:460〜480[1996]参照)。WU−BLAST−2は、複数の検索パラメーターを使用し、これらのうちのほとんどはデフォルト値に設定される。調製可能なパラメーターは以下の値に設定される:overlap span=1、overlap fraction=0.125、word threshold(T)=11。
HSP S及びHSP S2パラメーターは動的な値であり、特定の配列の構成及び、所望の配列を検索する特定のデータベースの構成に依存してプログラム自体により確立される。しかしながら、これらの値は、感度を上昇させるように調整することができる。
好ましくは、各クリーニング助剤は、組成物に使用されるプロテアーゼ酵素と適合性がある。
本発明は、1つ以上のプロテアーゼ変異体、すなわち新規ポリペプチドを含み、これを集合的に「本発明に使用されるポリペプチド」と呼んでもよい。本発明に使用されるポリペプチドとしては、酵素活性(例えばタンパク質分解活性)を有する、例えばサブチリシン変異体のような、単離された、組換え型の、実質的に純粋な、又は非天然の変異型プロテアーゼポリペプチドが挙げられる。一部の実施形態では、サブチリシン変異体、又は配列番号2の配列を有するGG36の変異体のようなポリペプチドは、その親、例えば配列番号2の配列を有するGG36プロテアーゼと比較して、改善されたクリーニング性能を有する。一部の実施形態では、上記ポリぺプチドは、クリーニング用途に有用であり、クリーニングする必要のある物品又は表面(例えば、物品の表面の)をクリーニングする方法に有用なクリーニング組成物中に組み込まれてもよい。
フェニルアラニン、チロシン、及びトリプトファンは、互いに保存的な置換を提供し得る。
AQSVPWGISRVQAPAAHNRGLTGSGVKVAVLDTGISTHPDLNIRGGASFVPGEPSTQDGNGHGTHVAGTIAALNNSIGVLGVAPSAELYAVKVLGASGSGSVSSIAQGLEWAGNNGMHVANLSLGSPSPSATLEQAVNSATSRGVLVVAASGNSGAGSISYPARYANAMAVGATDQNNNRASFSQYGAGLDIVAPGVNVQSTYPGSTYASLNGTSMATPHVAGAAALVKQKNPSWSNVQIRNHLKNTATSLGSTNLYGSGLVNAEAATR(配列番号2)である。
AQSVPYGVSQIKAPALHSQGYTGSNVKVAVIDSGIDSSHPDLKVAGGASMVPSETNPFQDNNSHGTHVAGTVAALNNSIGVLGVAPSASLYAVKVLGADGSGQYSWIINGIEWAIANNMDVINMSLGGPSGSAALKAAVDKAVASGVVVVAAAGNEGTSGSSSTVGYPGKYPSVIAVGAVDSSNQRASFSSVGPELDVMAPGVSIQSTLPGNKYGAYNGTSMASPHVAGAAALILSKHPNWTNTQVRSSLENTTTKLGDSFYYGKGLINVQAAAQ(配列番号1)である。
,T022A+S103A+G159D+S188D+Q245R+E271F,T022A+S103A+G159D+S188D+N248D+E271F,T022A+G159D+S188D+A232V+N248D,G159D+S188D+A232V+Q245R+N248D,T022A+V104I+G159D+S188D+Q245R+E271F,T022A+V104I+G159D+S188D+N248D+E271F,T022A+V104I+G159D+S188D+A232V+Q245R,S103A+G159D+S188D+Q245R+N248D+E271F,G159D+S188D+A232V+Q245R+E271F,G159D+S188D+A232V+N248D+E271F,T022A+S103A+G159D+S188D+A232V+N248D,V104I+G159D+S188D+Q245R+N248D+E271F,S103A+G159D+S188D+A232V+Q245R+N248D,T022A+G159D+S188D+A232V+E271F,T022A+G159D+S188D+Q245R+N248D+E271F,S103A+G159D+S188D+A232V+Q245R+E271F,T022A+V104I+G159D+S188D+A232V+N248D,V104I+G159D+S188D+A232V+Q245R+N248D,S103A+G159D+S188D+A232V+N248D+E271F,T022A+S103A+G159D+S188D+A232V+E271F,V104I+G159D+S188D+A232V+Q245R+E271F,V104I+G159D+S188D+A232V+N248D+E271F,T022A+V104I+G159D+S188D+A232V+E271F,G159D+S188D+A232V+Q245R+N248D+E271F,T022A+G159D+S188D+A232V+N248D+E271F,T022A+G159D+S188D+A232V+Q245R+E271F,T022A+G159D+S188D+A232V+Q245R+N248D,S101G+S103A+S188D,S101G+V104I+S188D,S101G+S103A+V104I+S188D(リスト9)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
T022A+S103A+V104I+S188D+Q245R+N248D,T022A+S103A+V104I+S188D+A232V+Q245R,T022A+S103A+V104I+S188D+Q245R+E271F,T022A+S103A+V104I+S188D+N248D+E271F,S103A+V104I+S188D+Q245R+N248D+E271F,T022A+S103A+V104I+S188D+A232V+N248D,S103A+V104I+S188D+A232V+Q245R+N248D,T022A+S103A+S188D+Q245R+N248D+E271F,T022A+V104I+S188D+Q245R+N248D+E271F,S103A+V104I+S188D+A232V+N248D+E271F,S103A+V104I+S188D+A232V+Q245R+E271F,T022A+S103A+V104I+S188D+A232V+E271F,T022A+S103A+S188D+A232V+N248D+E271F,T022A+S103A+S188D+A232V+Q245R+N248D,S103A+S188D+A232V+Q245R+N248D+E271F,T022A+V104I+S188D+A232V+Q245R+N248D,T022A+S103A+S188D+A232V+Q245R+E271F,T022A+V104I+S188D+A232V+N248D+E271F,T022A+S188D+A232V+Q245R+N248D+E271F,V104I+S188D+A232V+Q245R+N248D+E271F,T022A+V104I+S188D+A232V+Q245R+E271F,T022A+S103A+V104I+G159D+S188D+Q245R,T022A+S103A+V104I+G159D+S188D+N248D,S103A+V104I+G159D+S188D+Q245R+N248D,T022A+S103A+V104I+G159D+S188D+A232V,S103A+V104I+G159D+S188D+A232V+Q245R,T022A+S103A+G159D+S188D+Q245R+N248D,S103A+V104I+G159D+S188D+Q245R+E271F,T022A+S103A+V104I+G159D+S188D+E271F,S103A+V104I+G159D+S188D+A232V+N248D,T022A+V104I+G159D+S188D+Q245R+N248D,S103A+V104I+G159D+S188D+N248D+E271F,S103A+V104I+G159D+S188D+A232V+E271F,T022A+S103A+G159D+S188D+A232V+Q245R,T022A+S103A+G159D+S188D+Q245R+E271F,T022A+S103A+G159D+S188D+N248D+E271F,T022A+V104I+G159D+S188D+Q245R+E271F,T022A+V104I+G159D+S188D+N248D+E271F,T022A+V104I+G159D+S188D+A232V+Q245R,S103A+G159D+S188D+Q245R+N248D+E271F,T022A+S103A+G159D+S188D+A232V+N248D,V104I+G159D+S188D+Q245R+N248D+E271F,S103A+G159D+S188D+A232V+Q245R+N248D,T022A+G159D+S188D+Q245R+N248D+E271F,S103A+G159D+S188D+A232V+Q245R+E271F,T022A+V104I+G159D+S188D+A232V+N248D,V104I+G159D+S188D+A232V+Q245R+N248D,S103A+G159D+S188D+A232V+N248D+E271F,T022A+S103A+G159D+S188D+A232V+E271F,V104I+G159D+S188D+A232V+Q245R+E271F,V104I+G159D+S188D+A232V+N248D+E271F,T022A+V104I+G159D+S188D+A232V+E271F,G159D+S188D+A232V+Q245R+N248D+E271F,T022A+G159D+S188D+A232V+N248D+E271F,T022A+G159D+S188D+A232V+Q245R+E271F,又はT022A+G159D+S188D+A232V+Q245R+N248D(リスト10)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
S103A+V104I+S188D+A232V+Q245R,T022A+S103A+V104I+S188D+Q245R,T022A+S103A+V104I+S188D+N248D,S103A+V104I+S188D+Q245R+N248D,T022A+S103A+V104I+S188D+A232V,T022A+S103A+S188D+Q245R+N248D,T022A+V104I+S188D+Q245R+N248D,S103A+V104I+S188D+Q245R+E271F,S103A+V104I+S188D+A232V+N248D,T022A+S103A+V104I+S188D+E271F,S103A+V104I+S188D+N248D+E271F,S103A+V104I+S188D+A232V+E271F,T022A+S103A+S188D+A232V+Q245R,T022A+S103A+S188D+Q245R+E271F,T022A+S103A+S188D+N248D+E271F,T022A+V104I+S188D+A232V+Q245R,S103A+S188D+A232V+Q245R+N248D,S103A+S188D+Q245R+N248D+E271F,T022A+S103A+S188D+A232V+N248D,T022A+V104I+S188D+N248D+E271F,T022A+V104I+S188D+Q245R+E271F,V104I+S188D+A232V+Q245R+N248D,T022A+V104I+S188D+A232V+N248D,V104I+S188D+Q245R+N248D+E271F,T022A+S188D+Q245R+N248D+E271F,S103A+S188D+A232V+Q245R+E271F,S103A+S188D+A232V+N248D+E271F,T022A+S103A+S188D+A232V+E271F,V104I+S188D+A232V+N248D+E271F,V104I+S188D+A232V+Q245R+E271F,T022A+V104I+S188D+A232V+E271F,T022A+S188D+A232V+N248D+E271F,T022A+S188D+A232V+Q245R+N248D,S188D+A232V+Q245R+N248D+E271F,T022A+S188D+A232V+Q245R+E271F,T022A+S103A+V104I+G159D+S188D,S103A+V104I+G159D+S188D+Q245R,S103A+V104I+G159D+S188D+N248D,S103A+V104I+G159D+S188D+A232V,T022A+S103A+G159D+S188D+Q245R,T022A+V104I+G159D+S188D+Q245R,S103A+V104I+G159D+S188D+E271F,T022A+S103A+G159D+S188D+N248D,T022A+V104I+G159D+S188D+N248D,S103A+G159D+S188D+Q245R+N248D,V104I+G159D+S188D+Q245R+N248D,T022A+S103A+G159D+S188D+A232V,T022A+V104I+G159D+S188D+A232V,S103A+G159D+S188D+A232V+Q245R,V104I+G159D+S188D+A232V+Q245R,S103A+G159D+S188D+Q245R+E271F,S103A+G159D+S188D+A232V+N248D,T022A+G159D+S188D+Q245R+N248D,T022A+S103A+G159D+S188D+E271F,V104I+G159D+S188D+Q245R+E271F,T022A+V104I+G159D+S188D+E271F,V104I+G159D+S188D+A232V+N248D,S103A+G159D+S188D+N248D+E271F,V104I+G159D+S188D+N248D+E271F,S103A+G159D+S188D+A232V+E271F,V104I+G159D+S188D+A232V+E271F,T022A+G159D+S188D+N248D+E271F,T022A+G159D+S188D+A232V+Q245R,T022A+G159D+S188D+Q245R+E271F,G159D+S188D+Q245R+N248D+E271F,T022A+G159D+S188D+A232V+N248D,G159D+S188D+A232V+Q245R+N248D,G159D+S188D+A232V+Q245R+E271F,G159D+S188D+A232V+N248D+E271F,又はT022A+G159D+S188D+A232V+E271F(リスト11)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
D−S188D−A232T−Q245V−N248D−E271L,A016S−T022A−S101G−S103A−V104I−N116L−S128N−Y209V−A232V,T022A−S101G−S103A−V104I−G159D−S188E−A232S−Q245T−N248H−E271H,G020R−N062E−S078G−G118D−P129E−G159D−H249R,T022A−S101G−S103A−V104I−G159D−S188D−A232L−Q245R−N248E,G020R−S024R−S078G−G118D−G159D−S188D−Q245R,S024R−N062E−S078G−G118S−G159D−Q245R−N248D,G020R−S078G−G118S−G159D−S188D−Q245R,S024R−N062E−S078G−G118S−G159D−S188D,T022A−S101G−S103A−V104I−G159D−S188E−A232V−Q245R−N248H−E271H,G020R−S024R−N062E−S078G−G118D−G159D,T022A−S101G−S103A−V104I−G159D−S188D−A232T−V244A−Q245R−N248H−E271H,S024R−S078G−G118S−P129E−G159D−S188D−Q245R,T022Q−S101G−S103A−V104I−G159D−S188E−A232V−Q245V−N248D−E271F,G020R−S024R−N062E−S078G−G118D−G159D−S188D−Q245R,T022A−S024R−N062E−S128I−A158E,G020R−S024R−S078G−G118D−N248D−H249R,S024R−S078G−G118D−P129E−Q245R−H249R,T022A−S101G−S103A−V104I−G159D−S188D−A232T−Q236K−Q245T−N248E,N062E−S078G−G118S−G159D−Q245R−N248D,T033S−G118R−S166D,G020R−S024R−S078G−G118D−P129E−S188D−N248D,G020R−S078G−G118S−P129E−G159D−S188D−Q245R−N248D,A016S−T022A−S101G−S103A−V104I−L111V,T022Q−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248E−E271H,S024R−N116L−G118R−S128I−A158E−S188D−V199I,G020R−S024R−S078D−G118D−G159D−H249R,T022A−S101G−S103A−V104I−G159D−S188E−A232S−Q245R−N248E−E271T,G020R−S024R−S078D−G118S−S188D−N248D−H249R,T022A−S101G−S103A−V104I−G159D−S188D−A232T−Q245R−N248D−E271T,G020R−S024R−S078G−G118D−P129E−S188D−H249R,S024R−N062E−S078G−G118S−S188D−N248D,T022A−S101G−S103A−V104I−N116L−S128N−Y209A−G211Q−T213A−A232V,T022Q−S101G−S103A−V104I−G159D−S188D−A232T−Q245R−N248D−E271L,S024R−A048V−S078G−G118D−G159D−S188D−H249R,G020R−S024R−N062E−S078D−G118D,G102A−S103G−V104I,G020R−S024R−S078D−G118D−G159D−Q245R−N248D−H249R,T022A−T033S−G118R−A158E,T022A−S024R−N116L−S128I−S188D,G020R−S024R−S078D−G118D−P129E−G159D−Q245R−N248D−H249R,T022Q−S101G−S103A−V104I−G159D−S188E−A232T−Q245T−N248E−E271F,S024R−N062E−S078G−G118S−S188D−Q245R,S024R−N062E−S078G−G118D−G159D,G020R−S024R−N062E−S078D−G118S−P129E−G159D−Q245R,T022Q−S101G−S103A−V104I−G159D−S188E−A232S−Q245V−N248E−E271T,G020R−S078G−G118D−S188D−N248D−H249R,T022A−S024R−N062E−N116L−G118R−A158E−S166D−S188D,S078G−G118S−G159D−S188D−H249R,T022Q−S101G−S103A−V104I−G159D−S188E−A232T−Q245V−N248H−E271F,G020R−S078G−G118S−P129E−G159D−S240F−N248D−H249R,S024F−T033S−S101G−S103A−V104I−N116A−Y209A−G211Q−T213A−A232V,N062E−S078D−G118S−S188D−H249R,T022A−S101G−S103A−V104I−G159D−S188E−A232V−Q245V−N248D−E271T,G020R−S078G−G118S−G159D−S188D−Q245R−N248D,T022Q−S101G−S103A−V104I−G159D−S188D−A232T−Q245R−N248D−E271F,S024R−S078G−G118D−G159D−S188D−Q245R−N248D−H249R,G020R−S024R−N062E−S078D−G118D−Q245R,S024R−S078G−G118D−P129E−S188D−Q245R,N062E−S078G−G118S−S188D−Q245R−N248D−H249R,S024R−N062E−S078G−G118D−G159D−H249R,G020R−S078G−G118S−P129E−G159D−S188D−H249R,S024R−N062E−S078G−G118S−P129E−S188D−H249R,T022Q−S101G−S103A−V104I−G159D−S188E−A232L−Q245R−N248H,T022Q−S101G−S103A−V104I−G159D−S188D−A232V−Q245V−N248H−E271L,G020R−S101G−S103A−V104I−N116A−S128N−Y209V−G211Q−T213A−A232V,S024R−N062E−S078D−G118S−P129E−G159D−H249R,T022A−S101G−S103A−V104I−G159D−S188E−A232V−Q245R−N248D−E271H,G020R−N062E−S078G−G118D−P129E−S188D−H249R,T022Q−S101G−S103A−V104I−G159D−S188E−A232L−Q245V−N248E−E271L,G020K−T022L−S078G−G118S−P129E−G159D,S078G−G118S−S188D−Q245R−N248D,T022A−S024F−S101G−S103A−V104I−N116A−S128N−Y209A−A232V,G020R−S024R−N062E−S078G−G118S−G159D−N248D,N062E−G118R−S166D−S188D,T022Q−S101G−S103A−V104I−G159D−S188E−A232T−Q245R−N248E−E271T,T022A−S101G−S103A−V104I−G159D−S188D−A232S−Q245T−N248H−E271F,G020R−N062E−S078G−G118S−G159D−H249R,S024R−N062E−N116L−A158E,S024R−S078G−G118D−P129E−Q245R−N248D−H249R,G020R−S024R−N062E−S078D−G118S−P129E−S188D−Q245R,S024R−S078G−G118D−P129E−G159D−S188D−H249R,T022Q−S101G−S103A−V104I−G159D−S188E−A232L−Q245R−N248D−E271H,S024R−S078D−G118D−P129E−S188D−Q245R−N248D−H249R,G020R−S024R−S078G−G118D−P129E−G159D−N248D−H249R,T022A−S101G−S103A−V104I−G159D−S188E−A232V−Q245T−N248E−E271F,T022Q−S101G−S103A−V104I−G159D−S188D−A232L−Q245T−N248H−E271T,S024R−S078D−G118S−P129E−G159D,G020R−N062E−S078G−G118S−P129E−S188D−Q245R,T022A−S024R−N116L−G118R−S128I−S188D,T022A−S101G−S103A−V104I−G159D−S188E−A232L−Q245T−N248E−E271H,G020R−S024R−S078D−G118S−P129E−G159D−S188D−Q245R−N248D,G020R−S024R−N062E−S078G−G118S−P129E−S188D−N248D−H249R,T022A−S101G−S103A−V104I−G159D−S188E−A232V−Q245V−N248H−E271H,G020R−S078G−G118D−P129E−G159D−S188D−H249R,G020R−S024R−S078D−G118S−S188D−Q245R−H249R,T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248E−E271F,T022A−S101G−S103A−V104I−G159D−S188D−A232T−Q245R−N248D−E271F,S024R−N062E−S078G−G118S−S188D−N248D−H249R,G020R−N062E−S078G−G118S−G159D−Q245R,S024R−N062E−G118R−A158E−S166D−S188D,S024R−N062E−S078G−G118S−P129E−G159D−N248D−H249R,G020R−S024R−N062E−S078G−G118S−P129E−A158T−G159D−Q245R−N248D,T022Q−S101G−S103A−V104I−G159D−S188E−A232T−Q245R−N248E−E271L,G020R−S024R−N062E−S078D−G118S−S188D−H249R,S024R−S078G−G118S−S188D−N248D,T022A−S101G−S103A−V104I−G159D−S188E−A232L−Q245V−N248E−E271H,T022Q−S101G−S103A−V104I−G159D−S188D−A232L−Q245T−N248H−E271H,S099G−S101G,T022Q−S101G−S103A−V104I−G159D−S188D−A232T−Q245V−N248D−E271F,G020R−N062E−S078D−G118S−P129E−G159D−Q245R,T022A−S101G−S103A−V104I−G159D−S188E−A232T−Q245T−N248H−E
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G−G118S−P129E−S188D−N248D−H249R,S024R−S078D−G118D−G159D−S188D,A016S−S101G−S103A−V104I−N116L−Y209A−G211Q−A232V,S132D,N043K,G097P−V104L,A016S−T022A−S024F−S101G−S103A−V104I−N116A−Y209A−G211Q−A232V,S024R−N062E−S078D−G118D−G159D−S188D−H249R,S024R−S078G−G118S−G159D−S188D,S024R−S078G−G118D−G159D−S188D−N248D,S024R−N062E−S078G−G118S−G159D−S188D−Q245R−H249R,S024F−S101G−S103A−V104I−N116A−Y209V−T213A−A232V,G020K−S078N−S166D−T213A−L217E,S103A−L111V−L148I,S024F−T033S−S101G−S103A−V104I−N116L−S128N−Y209A−G211Q−T213A−A232V,S024R−S078D−G118D−G159D−S188D−Q245R−N248D,T022A−T033S−S101G−S103A−V104I−N116A−Y209V−T213A−A232V,S024R−N062E−S078G−G118D−P129E−S188D,S024R−S078D−G118D−P129E−S188D−Q245R−H249R,T022A−G118R−S166D,G020R−S024R−S078G−G118S−G159D−S188D−Q245R,T022A−S024R−T033S−N116L−G118R−A158E−S188D,T022Q−S101G−S103A−V104I−G159D−S188E−A232T−Q245V−N248D−E271F,G020R−S024R−S078D−G118S−P129E−Q245R−N248D−H249R,A016S−T022A−V104I−S128N,S024R−N062E−N076D−S101A−S103A−V104I−S188D−P210I−A232V−Q245R,T022L−G118R−S166D−T213A−L217E,S078D−G118S−P129E−G159D−S188D−Q245R−H249R,G195W−N269E,G020R−S024R−S078G−G118S−P129E−Q245V−N248E,N269W,T022A−T033S−G118R−A158E−S166D−S188D,G020R−N062E−S078G−G118D−P129E−G159D−Q245R−H249R,A016S−S101A−S103A,G097P−S099G−S103A−V104I,S024R−S078D−G118D−P129E−Q245R,T022Q−S101G−S103A−V104I−G159D−S188D−A232L−Q245R−N248E,S078G−G118D−P129E−S188D−Q245R,T033S−N062E−G118R−A158E,G020R−S078D−G118S−G159D−N248D,A016S−T022A−S103G−V104I−S128N−L148I,A016S−S101G−S103A−V104I−N116A−Y209A−A232V,S101A−S103A−V104I−S188D−M222S−A232V−Q245R,T022A−S024F−S101G−S103A−V104I−N116A−S128N−Y209V−T213A−A232V,A016S−T022A−S024F−S101G−S103A−V104I−N116A−Y209A−T213A−A232V,T022A−S101G−S103A−V104I−G159D−S188D−T213A−A232V−Q245R−N248D−E271F,A016S−S101G−S103A−V104I−N116L−Y209A−T213A−A232V,G020R−S078D−G118S−S188D,G020R−S078D−G118S−P129E−Q245R−N248D,T022L−S166D−T213A,G020R−S024R−S078D−G118S−P129E−G159D−S188D−N248D,S240G,S078G−G118S−P129E−Q245R−N248D,S024R−S078D−G118D−P129E−G159D−Q245R−N248D,S024R−S078G−G118S−G159D,T022A−S024R−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F−A272V,N062E−S078G−G118S−P129E−S188D−Q245R−N248D−H249R,S024F−S078N−G118R−S166D,S078G−G118S−P129E−N248D,N155W,A016S−S024F−S101G−S103A−V104I−N116A−S128N−Y209V−G211Q−T213A−A232V,G020R−N062E−S078D−G118D−P129E−Q245R−N248D,G020R−S078D−G118D−P129E−S188D−Q236R−N248D−H249R,T022A−S024R−N116L−A158E−S188D,S101G−S103A−V104I−N116A−S128N−Y209V−G211Q−T213A−A232V,S078D−G118S−S188D−Q245R−N248D,T022L−S024F−S078N−L217E,S099A−S101A−G102A,G020R−S078D−G118D−G159D−N248D−H249R,T022A−N076D−S101G−S103A−V104I−I107V−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,T033S−N116L−G118R−S166D−S188D,S024R−G118R−S128I−A158E−S166D−S188D,G020R−S024R−N062E−S078G−G118S−P129E−G159D−Q245R−N248D−H249R,N062E−S078G−G118D−N248D−H249R,N062E−S078R−P129E−S188D−Q245R−N248D,S024R−N062E−G159D−S188D−Q245R,G020R−N062E−G118R−S188D−N248D−H249R,N062E−S078R−P129E−G159D,G020R−S024R−N062E−P129E−S188D−N248D,N062E−S078R−G118R−G159D−S188D−P210L−N248D,N062E−S078R−Q245R−N248D,G020R−G159D−S188D−H249R,G020R−G118R−G159D−S188D−N248D,G118R−P129E−G159D−S188D−H249R,N062E−S078R−G118R−P129E−N248D,N062E−S078R−G159D,N062E−G118R−P129E−S188D−Q245R,G020R−S024R−P129E−G159D−S188D−N248D,S024R−N062E−S078R−G159D−N248D,G020R−P129E−S188D−H249R,G020R−P129E−G159D−S188D−Q245R,A016S−S024F−S101G−S103A−V104I−N116A−S128N−S188D−Y209V−T213A−A232V,G020R−G159D−S188D−Q245R−N248D,G118R−P129E−G159D−Q245R−N248D,G020R−N062E−S078R−P129E−S188D−N248D,G020R−P129E−S188D−Q245R,S024R−N062E−S188D−N248D,S078R−L111I−N185I−I198L−L217E,G020R−P129E−S188D−N248D−H249R,G020R−N062E−G118R−G159D−N248D,G020K−T022L−G118R−P129E−S188D,G020R−G118R−P129E−S188D,G020R−P129E−G159D−Q245R−N248D,G020R−S024R−P129E−G159D,G020R−P129E−G159D−Q245R−N248D−H249R,S024R−P129E−G159D−S188D−Q245R−N248D−H249R,G020R−P129E−Q245R−N248D,N062E−S078R−G159D−N248D,S024R−G118R−P129E−G159D−S188D−Q245R−N248D−H249R,G020R−G061W−P129E−G159D−S188D−Q245R,T022A−S101G−S103A−V104I−G159D−S188D−M222S−A232V−Q245R−N248D−A270V−E271F,N062E−G159D−S188D−H249R,A016S−S024F−S101G−S103A−V104I−N116A−S128N−S130D−Y209V−T213A−A232V,G020R−S024R−P129E−G159D−N248D−H249R,P129E−G159D−S188D−H249R,G118R−P129E−G159D−S188D−K237R−N248D−H249R,G020R−G159D−S188D−Q245R,G020R−S188D−Q245R−N248D−H249R,T022A−S101G−S103A−V104I−P129S−L217Q−A232V−Q245R,G020R−S078R−G118R−P129E−S188D−N248D,G020R−S024R−G118R−G159D−S188D−Q245R−N248D,G020R−G118R−P129E−G159D−S188D,G020R−G159D−S188D,G020R−G118R−P129E−S188D−N248D,A016S−S024R−S101G−S103A−V104I−N116A−S128N−Y209V−T213A−A232V,G020K−N062E−S188D−T213A−M222S,A016S−S024F−S101D−S103A−V104I−N116A−S128N−Y209V−T213A−A232V,S024G−S078N−S101N−Q109G−S128A−L217Q,T022A−G097S−S101N−S103A−V104I−S128A−G159D−S188D−L217Q−M222S−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−G159D−S188D−M222S−A232V−Q245R−N248D−E271F,G020R−P129E−Q245R,S024R−P129E−G159D−Q245R−N248D,S024R−G118R−S188D−N248D,G020R−P129E−H249R,S024R−P129E−Q245R−N248D,T022A−S101G−S103A−V104I−L217Q−A232V−Q245R,G020R−S078R−P129E−G159D−S188D−H249R,T022A−S101G−S103A−V104I−S128A−P129S−L217Q−A232V−Q245R,G118R−P129E−H249R,G020R−N062E−G118R,G020R−G118R−P129E−G159D−Q245R−N248D,T022A−S101Q−S103A−V104I−P129S−L217Q−A232V−Q245R,S024R−S078R−G118R−P
129E−G159D−S188D,P129E−Q245R−N248D−H249R,S024G−G061S−S078N−S101N−Q109G−S128A−L217Q−N243V,S078R−V084A−P129E−Q245R,S024R−G118R−G159D−S188D−N248D,G020R−G118R−P129E−G159D−H249R,S078R−P129E−G159D,G061P−S078N−G097A−S101N−S128A−V203Y−L217Q,P086S−S087G−A088V−G097A−N117S−S128A−L217Q,S024R−S078R−G159D−S188D−Q245R−N248D−H249R,S078R−G118R−P129E,S024G−S078N−S101N−S128A−L217Q−N243V,S024R−S078R−G159D−S188D,G020R−G118R−P129E,G020R−S024R−P129E−G159D−S188D−H249R,S024R−G118R−G159D−S188D,S024R−G118R−P129E−G159D−S188D−Q245R−N248D,S024G−S078N−S101N−S128A−L217Q,S024R−G159D−S188D−Q245R,S024G−S078N−S101N−Q109G−L217Q−N243V−N248A,G020R−S078R−G159D−S188D−Q245R−N248D,S078R−G118R−P129E−S188D−N248D,S024R−S188D−Q245R−N248D,G020R−S024R−S101A−P210I−G211Q,G020R−G159D−N248D−H249R,G020R−P129E,G020K−N062E−N116L−T213A−M222S,S024G−S078N−A088T−S101N−Q109G−N116T−S128A−A158S−L217Q−N218S−L257G,A016S−S024F−S101G−S103A−V104I−N116A−S128N−S166D−Y209V−T213A−A232V,S024R−N062E−S078R−P129E−H249R,N018K−G020R−S024R−R045T−S101A−P210I−G211Q−T213A,G020R−S024R−G118R−P129E−G159D−S188D−N248D−H249R,G020R−S024R−P129E−H249R,G020R−G118R−S188D−Q245R−N248D−H249R,G020R−S024R−N062E−S078G−G118S−Q245R,G020R−S024R−G118R−P129E−G159D−N248D,S024G−S078N−S101N−Q109G−S128A−L217Q−S256R,S024G−S078N−S101N−S128A−A158S−L217Q−L257G,G020R−S024R−G118R−S188D−N248D,G020R−G118R−G159D−S188D−Q245R−N248D−H249R,G159D−S188D−Q245R−N248D,S078N−G118R−S166D−L217E−M222S,G020R−G118R−P129E−G159D−Q245R−N248D−H249R,T022A−S101Q−S103A−V104I−L124V−S128A−P129S−A232V−Q245R,S024R−N062E−Q245R,S188D−Q245R−N248D,S024R−G118R−P129E−S188D−H249R,T022A−G097A−S101Q−S103A−V104I−P129S−A232V−Q245R,G020R−G118R−S188D−Q245R−N248D,S024G−S078N−S101N−Q109G−N116T−S128A−L217Q−N243V−S256R,G020R−G118R,G020R−S024R−S188D,N062E−P129E−G159D−S188D−Q245R,G020R−G159D−Q245R−N248D,G020R−N043R−S101A−P210I−G211Q,G097A−S101N−S128A−L217Q,G020R−G118R−S188D−N248D,S024R−S188D−N248D,G020R−S024R−S188D−Q245R−N248D,G020R−S024R−G118R−P129E−G159D−N248D−H249R,G020R−P129E−N248D,G159D−S188D,P129E−G159D,G020R−S188D−H249R,P129E−G159D−Q245R−N248D,G020R−G118R−G159D−N248D−H249R,G118R−S188D−N248D−H249R,G020K−S101D−G102A−L217E−S240R,N043R−G102A−L217E,N062E−S078N−S101D−S240R,G102A−L217E,G020K−S128L−L217E−S240R,G020K−N062E−S078N−L217E−S240R,N043R−S101D−S128L−L217E−S240R,G020K−S078N−S101D−G102A−P210L,N043R−S101D−L217E,G020K−G100S−L217E−S240R,S078N−G100S,G020K−N043R−S101D−G102A−L217E,G100S−S240R,G020K−G102A−L217E,G020K−S024G−N062E−S078N−S101N−Q109N−N116L−S128A−S188D,G020K−L217E−S240R,N043R−S101D,N043R−S078N−S101D−S128L−S240R,N043R−S078N−S101D−L217E−S240R,G020K−S078N−S101D,N043R−S128L−S240R,G020K−N062E−N116L−N123G−T213A,G020K−N062E−G097S−S101G−Q109G−N116L−S128A,G020K−N062E−S078N−G097A−S101N−Q109N−N116L−S188D,N043R−S078N−S101D−G102A−L217E,G020K−S078N−S099G−S128L−L217E,G020K−N062E−S101D,G020K−S128L−L217E,G020K−S024G−N062E−S078N−G097S−S101G−Q109G−N116L−L217Q,N043R−G097A−S101D−S128L,G020K−S024G−N062E−S101Q−Q109N−N116L−S128A,G020K−S024G−N062E−S078N−S101N−N116L−S128A−L217Q,S078N−G102A−S240R,N043R−S078N−G100S−L217E−S240R,G020K−S078N−S128L−L217E−S240R,G020K−N062E−N116L−S128Q,G020K−S101G−L217E−S240R,G020K−S024G−N062E−S101N−Q109G−N116L−S128A−L217Q,G020K−N062E−S078N−G097S−S101N−N116L−L217Q,G020K−N062E−G097S−S101N−Q109G−N116L−L217Q,G020K−S024G−N062E−S078N−G097A−S101Q−Q109N−N116L−M222S,G020K−S024G−N062E−S078N−G097S−S101Q−Q109N−N116L−S128A−S188D−L217Q,G020K−N062E−S078N−S101N−Q109G−N116L−S188D−L217Q,又はG020K−N062E−S105G−N116L−S128L−T213A(リスト14)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
G020K−T213A−L217E,S024R−N062E−S078D−G118S−P129E−G159D−S188D−Q245R−N248D−H249R,S078N−S166D−T213A−L217E,S078D−G118S−P129E−G159D−Q245R−H249R,T022A−N076D−S101G−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D−E271F−A272V,G020K−T022L−G118R−L217E,T022A−V104L−L111V,T022A−S101G−S103A−V104I−S128A−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,S024R−N062E−S078G−G118S−P129E−S188D−N248D,G020R−S024R−S078D−G118D−G159D−S188D−N248D,T022L−S078N−L217E,G020R−S024R−S078G−G118S−S188D,S024F−S101G−S103A−V104I−N116L−Y209V−G211Q−T213A−A232V,T022A−N116L−G118R−A158E−S166D,G020R−S024R−S078G−G118S−P129E−S188D−Q245R−N248D−H249R,T022A−V104I−S128N,S024R−S078G−G118D−Q245R,N062E−S078G−G118S−P129E−G159D−S188D−H249R,T022A−S101G−S103A−V104I−I107V−G159D−S188D−A232V−Q245R−N248D−A270V−E271F−A272V,S024R−N062E−S078D−G118S−P129E−G159D−Q245R−N248D−H249R,T022A−T033S−G118R−A158E−S188D,T022A−S078N−G097A−S101N−S103A−V104I−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024R−S166D−S188D,A016S−S024F−T033S−S101G−S103A−V104I−N116L−Y209A−A232V,T022A−T033S−S128I−A158E,S024R−T033S−N116L−S188D,N062E−N076D−S101A−S103A−V104I−P210I−A232V−Q245R,T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−A270V−E271F−A272V,S130D,G020K−T022L−S024F−S078N−G118R−S166D−L217E,T022Q−S101G−S103A−V104I−G159D−S188E−A232S−Q245V−N248E,S024R−T033S−N116L−S166D−S188D,S024R−S078D−G118S−S188D−Q245R−H249R,T022A−S024R−T033S−A158E−S166D−S188D,G020K−T022L−S024F−S166D−T213A−L217E,T022A−N062E−N116L−G118R−S188D,G020R−S078G−G118D−Q245R−N248D−H249R,T022A−N116L−G118R−S128I,T022L−S078N−S166D,T022L−G118R−S128D,G097P−S099A,T022L−S024F−G118R−S128D,S242K,N062E−S078D−G118S−G159D,A016S−S103G−S128N−L148I,G097P−A098Q−S101A,T022A−S103A−V104L−S128N−L148I,T022A−S101G−S103A−V104I−G118R−G159D−S188D−T213A−A232V−Q245R−N248D−E271F,S099G−S101G−G102A,T022Q−S101G−S103A−V104I−G159D−S188D−A232L−Q245T−N248D,G100S−S101G−V104I,S078D−G118S−G159D−Q245R−N248D,A016S−S024F−T033S−S101G−S103A−V104I−N116A−Y209V−G211Q−T213A−A232V,T022A−S024R−T033S−N116L−A158E,T022A−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F−A272V,T022A−S024R−N116L−S128I−S166D,S101G−S103A−V104I−N116L−S128N−Y209V−A232V,S024F−S101G−S103A−V104I−N116L−Y209A−A232V,G020R−S078G−G118D−G159D−S188D−N248D,G020R−S078D−G118D−S188D−Q245R−N248D,S024F−S078N−G118R−S128D,T022L−S024F−S078N−G118R−S166D,G020R−S024R−S078D−G118S−P129E−G159D−S188D−Q245R−H249R,S103A−V104L−S128N,T022A−S024R−N062E−N116L−S128I,T022A−N062E−N116L−G118R−A158E−S188D,T022A−S024G−G097S−S101G−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,G020R−S024R−N062E−S078D−G118D−G159D−S188D−Q245R−H249R,N062E−S078D−G118S−S188D−Q245R−N248D,T022A−S103A−L148I,T022A−S024R−N116L−S128I−A158E−S188D,G097P−S099T−S101G−V104I,S166D−T213A−L217E,A016S−T033S−S101G−S103A−V104I−N116L−Y209V−A232V,N062E−S078D−G118S−P129E−G159D−S188D−Q245R,T022A−S024F−S101G−S103A−V104I−N116A−S128N−Y209A−G211Q−A232V,G020K−T022L−S078N−G118R−S128D−S166D−L217E,T033S−S188D,T033S−N116L−G118R−A158E,T022A−S024G−N076D−V093I−S101N−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,G020R−S078D−G118S−P129E−Q245R−H249R,T022A−S024R−A158E−S166D−S188D,G020K−T022L−S078N−G118R−S128D,G020R−S024R−S078D−G118D−P129E−S188D,S099T−G102A,S024R−N116L−G118R−A158E−S188D,T033S−N116L−G118R−S166D,T022A−S101G−S103A−V104I−G159D−S188D−A232L−Q245V−N248H,S078D−G118D−Q245R,G020K−S078N−G118R−S166D−T213A−L217E−A272D,A016S−T022A−V104L−L111V−L148I,T022Q−S101G−S103A−V104I−G159D−S188D−A232V−Q245V−N248H,N062E−N116L−G118R−S166D,N062E−S166D,T022A−S024R−N062E−G118R−A158E−S188D,T022A−S024F−S101G−S103A−V104I−N116A−Y209V−A232V,T022A−S024R−N076D−S101G−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D−A270V−E271F,G020R−S024R−N062E−S078G−G118D−Q245R,S024R−N116L−S128I−A158E−S188D,S024R−N062E−S101A−S103A−V104I−P210I−A232V−Q245R,A114T,T022L−S024F−S078N−G118R−S128D,S024R−N116L−G118R−S166D,N062E−S078G−G118D−P129E,A016S−T022A−S101G−S103A−V104I−N116L−Y209A−G211Q−A232V,G020K−T022L−S078N−S166D,G020R−S024R−N062E−S078G−G118S−P129E−S188D−Q245R−N248D−H249R,T022A−S078N−G097A−S101Q−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S101G−S103G,A016S−S024F−S101G−S103A−V104I−N116L−S128N−Y209A−G211Q−S212L−A232V,S024F−G118R−S166D−T213A,G100S−S101G,A016S−T022A−S103A−V104L−S128N,G020K−S024F−S078N−G118R−S166D,S099T−G102A−S103G,G020K−S024F−S128D−L217E,S078D−G118D−G159D−H249R,N062E−S078G−G118D−S188D,N076D−S101A−S103A−V104I−P210I−A232V−Q245R,S024R−S078G−G118D−P129E−N248D,S078G−G118S−G159D−S188D,A016S−S101G−S103A−V104I−N116L−S128N−Y209V−G211Q−T213A−A232V,G020K−S078N−G118R−S166D−T213A−L217E,T022A−S101N−S103A−V104I−L124V−P129S−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101N−S103A−V104I−P129S−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,S024R−S078D−G118D−P129E,G020K−S024F−S128D−T213A,T022A−T033S−A158E−S188D,G020K−S024F−S128D−S166D−T274A,S024R−N062E−N116L−G118R−S128I−A158E−S166D−S188D,S078G−G118S−P129E−S188D,T022A−S024R−S128I−A158E−S188D,T022A−S024R−G118R−S128I−A158E,T022A−N116L−S166D,G020K−G118R−S128D−S166D,G020K−T022L−S024F−S078N−G118R−S128D−L217E,G020R−S024R−S078D−G118D−P129E−S188D−N248D,G020K−T022L−G118R−S128D−L217E,S024F−S078N−G118R−S128D−T213A,S024R−S078G−G118D−S188D−N248D,N062E−N076D−S101A−S103A−V104I−S188D−A232V−Q245R,T03
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2V−Q245R−N248D−E271F,T022A−N076D−G097S−S101Q−S103A−V104I−Q109N−G159D−S188D−A232V−Q245R−N248D−E271F,G020R−S024R−S078D−G118S−N248D,T022Q−S101G−S103A−V104I−G159D−S188D−A232S−Q245V−N248D−E271T,S078G−G118D−S188D−Q245R−N248D,T022A−N076D−S078N−G097S−S101N−S103A−V104I−Q109G−G159D−S188D−A232V−Q245R−N248D−E271F,G118R−S128D−S166D−L217E,G020R−S078G−G118S−P129E−Q245R−H249R,A016S−S024F−S101G−S103A−V104I−N116A−S128N−Y209V−T213A−A232V,T022A−S078N−S101Q−S103A−V104I−R145K−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−N043R−N076D−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−E271F,T022A−G097A−S101Q−S103A−V104I−L126I−P129S−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−G097A−S101N−S103A−V104I−Q109N−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−S078N−S101N−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−N076D−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−E271F−A272V,T022L−S078N−T213A,T022A−N076D−S078N−G097A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S078N−S101G−S103A−V104I−Q109G−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,N062E−S078G−G118S−P129E−G159D−Q245R−H249R,A016S−S101G−V104I−S128N−L148I,T022A−G118R−S188D,T022A−G097A−S101Q−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,G020K−S024F−G118R−S128D−T213A,T022A−S101Q−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,G020K−T022L−S024F−S078N−S128D−T213A−L217E,T022A−S024G−S078N−G097A−S101Q−S103A−V104I−Q109G−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,A016S−S101G−S103A−V104I−N116L−Y209V−G211Q−A232V,T022A−S024G−G097A−S101Q−S103A−V104I−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S101N−S103A−V104I−L124V−S128A−P129S−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,S099G−G100S−S103A,T022Q−S101G−S103A−V104I−S166D−S188E−A232T−Q245T−N248E,T022A−S024G−N076D−S078N−G097S−S101N−S103A−V104I−Q109N−G159D−S188D−A232V−Q245R−N248D−E271F,A098F−S099T−S103A−V104I,G020K−T022L−N062E−S078D−G118D−P129E−Q245R−N248D,T022L−S078N−G118R−S128D,T022A−S101G−S103A−V104I−N116L−Y209A−G211Q−T213A−A232V,T022A−S101Q−S103A−V104I−L126I−S128A−P129S−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,G023A−S024F−S101G−S103A−V104I−N116A−Y209V−A232V,T022A−S024R−N116L−G118R−S166D,S024R−N062E−S078D−G118D−P129E−G159D−Q245R−N248D−H249R,G020K−T022L−S024F−S078N−G118R−S128D−T213A,T022A−S024G−N076D−S078N−G097A−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−S101N−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F−T274I,G097P−S099A−V104L,G097P−S099A−S103A,T022A−S024G−S078N−G097S−S101Q−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−V104L−L148I,T022A−S024G−G097A−S101N−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−S101G−S103A−V104I−P129E−G159S−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−S078N−S101G−S103A−V104I−Q109G−G159D−S188D−A232V−Q245R−N248D−E271F,S024R−S078D−G118S−G159D−Q245R−H249R,T022W−N043R−R045T−S101A−P210I−T213A,S024G−N076D−S078N−S101N−H120Q−S128A−L217Q,G020R−S024R−G118R−P129E−G159D−H249R,G020R−S078R−G159D−S188D,P129E−S188D−Q245R−H249R,S078R−P129E−Q245R,S078R−P129E−N248D,T022A−S101Q−S103A−V104I−P129S−A232V−Q245R,S188D−N248D,S078R−G118R−G159D,G020R−S078G−G118S−Q245R−N248D−H249R,S024R−S078R−G118R−G159D,G020R−P129E−G159D−N248D,G020R−S024R−G159D−N248D,G097A−S128A−L217Q,S024R−P129E−G159D−N248D,T022K−S101A−S103N−V104L−A232T−Q245R,S078G−G118S−S188D−Q245R−H249R,S099T−S101G−G102A−S103A,G020R−G118R−G159D−Q245R,S024G−S078N−S101N−L217Q,S024G−S078N−S101N−S128A−L217Q−S256R,S078R−G118R−G159D−N248D,S078G−G118S−Q245R−H249R,G118R−P129E−N248D,G020K−T022L−Q245R,A098Q−S099T−S101G−S103A,G118R−H249R,S024R−G118R−N248D−H249R,G020R−S024R−S078G−G118S−Q245R−N248D−H249R,A098F−S099A−S101G−V104I,G020R−T022W−S024R−N043R−R045T−S101A−G211Q,A098Q−S099G−S101G−V104L,G020K−N062E−G097A−S101Q−Q109G−N116L−S188D−L217Q,G020K−N062E−S078N−G097A−S101Q−Q109G−N116L,G020K−N062E−G097A−S101Q−Q109N−N116L−L217Q,N043R−S078N−G102A−S128L−L217E−S240R,S078N−G097S−S101Q,N043R−N062E−S078N−S101D−S128L−S240R,S128L−L217E−E271L,G020K−S024G−N062E−G097S−S101N−Q109N−N116L−S128A−L217Q,G020K−N062E−N116L−S128L−T213A,S078N−G097A−S101G−Q109G−S188D−L217Q,S101D−S128L−L217E−S240R,G020K−S024G−N062E−G097A−S101Q−Q109G−N116L−S128A,G020K−N062E−S078N−G097S−S101N−Q109N−N116L−S128A−S188D−L217Q,G020K−N062E−G097S−S101Q−Q109G−N116L−S128A−S188D−L217Q,G020K−S024G−N062E−S078N−G097S−S101N−Q109N−N116L−S128A,S024G−S078N−G097S−S101G−S128A−S188D−L217Q,S024G−S078N−G097A−S101N−Q109G−S128A−S188D−L217Q,G020K−N043R−G102A−S128L,G020K−S078N−S101D−G102A−L217E−S240R,G020K−N062E−G100S,S078N−S128L−L217E−E271L,S128Q−L217E−E271L,G020K−S024G−N062E−S078N−G097A−S101N−N116L−S128A−L217Q,G020K−S024G−N062E−S078N−G097S−S101G−N116L−S128A−L217Q,G020K−S078N−S101D−G102A−L217E,G020K−N062E−S128L,G020K−N062E−S078N−S101G−Q109N−N116L,G020K−S024G−N062E−S078N−G097S−S101Q−N116L−S128A−L217Q,S078N−S128L−L217E−S240R,S101D−S128Q−L217E−S240R−E271L,N043R−G102A−S240R,G020K−N062E−S078N−S101N−Q109N−N116L−M222S,G020K−N062E−S101N−Q109G−N116L−S128A−L217Q,G020K−S024G−N062E−S078N−G097A−S101G−N116L−L217Q,G020K−N062E−S101G−N116L−S188D,G020K−N062E−G097S−S101Q−Q109N−N116L−S128A−S188D,G020K−I035V−G100S−S128L−L217E,N043R−S101D−G102A−S240R,N062E−S078N−G100S,G020K−N043R−N062E−A215T,N062E−S240R,
N043R−S128L−L217E−S240R,N062E−S101D−S240R,G020K−S101D−N116L−T213A,G020K−S101D−N116L−S128Q−P210S−T213A,G020K−S101D−T213A,G020K−S024G−N062E−S078N−G097S−S101Q−Q109N−N116L−S128A,G020K−N062E−S078N−G097S−S101Q−N116L−S128A−L217Q,S024G−G097S−S101N−Q109G−S188D−L217Q,G020K−S024G−N062E−S101N−Q109G−N116L−L217Q,L217E−S240R,S101D−L217E−S240R−E271L,N043R−N062E−S101D−S128L−S240R,G097A−S101N−S128A−S188D−L217Q,G020K−N062E−S078N−S101N−N116L−S128A−L217Q,G020K−N062E−S078N−G097S−S101G−Q109N−N116L−L217Q,G020K−S024G−N062E−G097S−S101N−Q109G−N116L−S128A−L217Q,G020K−S024G−N062E−G097S−S101G−Q109G−N116L−S128A−S188D−L217Q,G020K−N062E−S101N−Q109N−N116L−S128A−S188D,S078N−G097S−S101N−Q109N−S128A−S188D−L217Q−W241L,G020K−N043R−N062E−S078N−S101D,G020K−N062E−S101D−S240R,G020K−S101D−S128Q,G020K−N116L−S128Q−Y209H−T213A,G020K−N043R−S078N−G100S−L217E−N218D,S024G−S101N−Q109G−S128A−S188D−L217Q,G020K−S024G−N062E−S078N−G097S−S101N−Q109G−N116L−S128A−S188D,S078N−S101N−Q109G−S188D−L217Q,G020K−S024G−N062E−S078N−G097S−S101N−Q109G−N116L−S188D−L217Q,G020K−N062E−S078N−S101Q−Q109N−N116L−S128A−S188D−L217Q,G020K−N062E−S101G−Q109G−N116L,G020K−S024G−N062E−G097S−S101N−Q109G−N116L−S128A−S188D−M222S,S024G−G097A−S101G−S188D−L217Q,S024G−S078N−G097A−S101G−S128A−S188D,G097S−S101N−Q109G−S128A−S188D,G020K−S078N−S101D−I246T,N043R−S128L−L217E,G020K−S101D−L217E−S240R,S128L−L217E−T224A−E271L,G020K−S078N−S101D−S128Q−L217E−E271L,N062E−S078N−S101D−L217E−S240R,G020K−S101D−L217E−E271L,G020K−S078N−S128Q−L217E−S240R,G020K−N062E−S101D−N116L−T213A,G100S−S101D,S078N−G097S−S101G−S128A−L217Q,G020K−N062E−G097S−S101N−N116L−S128A−L217Q,G020K−N062E−G097S−S101N−N116L−L217Q,S101N−Q109G−S188D,G020K−S024G−N062E−G097S−S101Q−Q109N−N116L−S128A−L217Q,G020K−S024G−N062E−G097S−S101N−N116L,G020K−S024G−N062E−S101N−N116L−S128A,G020K−S024G−N062E−S078N−S101Q−Q109N−N116L−S128A,G020K−N062E−S078N−S101N−Q109G−N116L−S188D,G020K−N062E−S078N−S101N−Q109G−N116L−S128A,G020K−S024G−N062E−S078N−G097S−S101N−Q109G−N116L−S128A−M222S,G020K−S024G−N062E−S078N−G097S−S101G−N116L−S128A,S024G−S078N−G097S−S101Q−Q109G−S128A−S188D−L217Q,S024G−S078N−S101G−Q109N−S188D−L217Q,S024G−S078N−G097A−S101G−Q109G−S188D,S078N−S101D−S128Q−L217E−S240R−E271L,G020K−S128Q−L217E,S128Q−L217E−S240R−E271L,G020K−S078N−S101D−L217E,G020K−S078N−S101D−L217E−E271L,G020K−N116L−S128Q−T213A,G020K−N116L−N123G,S101G−S188D−L217Q,G020K−S024G−N062E−S078N−S101G−N116L−L217Q,S078N−G097A−S101G−Q109N−S128A−S188D,G020K−S078N−S128L−L217E−E271L,G020K−N062E−S101Q−Q109G−N116L,G020K−S101D−L217E,S024G−G097A−S101N−Q109N−S128A,G020K−S078N−S101D−S128L−L217E−S240R,G097A−S101G−L217Q,S024G−S101Q−Q109G−S128A−L217Q,G020K−S024G−N062E−T071A−S078N−G097S−S101G−N116L−L217Q,G020K−S024G−N062E−S078N−S101G−N116L−S128A,G020K−S024G−N062E−S078N−G097A−S101N−N116L,G020K−N062E−G097A−S101N−N116L,G020K−S024G−N062E−G097A−S101N−Q109G−N116L−S128A,G020K−S024G−N062E−S078N−G097S−S101G−Q109N−N116L,G020K−N062E−S078N−G097S−S101Q−Q109G−N116L−S128A−S188D−L217Q,G020K−N062E−S101N−Q109G−N116L−L217Q,G020K−S024G−N062E−G097A−S101N−Q109G−N116L−S188D−L217Q,G020K−S024G−N062E−S101G−N116L,S078N−G097S−S101N−Q109G−G159D−L217Q,S024G−G097A−S101N−Q109G−S188D,S078N−S101G−S128A−L217Q,S078N−G097A−S101N−S128A−S188D−L217Q,S024G−G097S−S101G−S128A−S188D−L217Q,S024G−S078N−G097S−S101Q−Q109G−S128A−S188D−L217Q−V227A,G020K−N062E−S078N,S078N−S128L−L217E−S240R−E271L,G020K−N062E−I072N−S101D−N116L−S128Q,G020K−T057P−N062E−N116L−S128Q−T213A,G020K−N043R−S078N−S101D−S240R,S078N−G097S−S101N−Q109N−S128A−S188D−L217Q,S024G−S101N−Q109N−S128A−S188D,G020K−S024G−N062E−G097S−S101Q−N116L−S128A,S024G−S078N−G097S−S101N−Q109N−S128A−S188D,N043R−G100S,G020K−N062E−S078N−S101Q−Q109G−N116L−S128A,S078N−S101Q−Q109N−S188D−L217Q,G020K−N116L−S128L−T213A,G020K−S078N−S101D−L217E−S240R,G020K−N062E−S101N−Q109N−N116L−M222S,G020K−S024G−N062E−G097A−S101Q−Q109N−N116L−S128A,S078N−G097S−S101G−S128A−S188D,G097S−S101G−Q109N−S128A−M222S,S024G−S078N−G097A−S101Q−S128A−M222S,G097A−S101G−Q109N−L217Q,S024G−S078N−S101G−S128A−S188D−L217Q,S024G−G097A−S101N−Q109G−S128A−S188D,G097S−S101N−Q109G−S128A,S078N−G097A−S101Q−L217Q,G020K−N043R−S078N−S101D,G020K−N043R−E054D−N062E−S078N−S240R,G020K−S101D−S240R,S128Q−L217E−S240R,G020K−S128Q−L217E−V244A−E271L,G020K−L217E−E271L,G020K−S078N−S128L−L217E,S078N−S101D−S128Q−L217E−E271L,G020K−N062E−L217E−E271L,G020K−N062E−S101D−N116L−S128Q−T213A,G020K−N062E−S078N−N116L−S128I,G020K−N062E−S078N−S128Q−T213A,S024G−G097A−S101G−Q109G−S128A,S024G−G097S−S101N−Q109N−S128A−L217Q,G020K−S024G−N062E−S078N−S101N−N116L−S128A−S188D−L217Q,G020K−S101D,G020K−N062E−S078N−G097S−S101Q−N116L−S128A,G020K−N062E−G097S−S101G−N116L−S188D,N043R−S078N−G100S−S128L−S240R,G097S−S101N−Q109N−S188D,G097S−S101Q−Q109N−S128A−L217Q,G020K−N062E−S101N−Q109G−N116L−S128A−S188D−M222S,G020K−S024G−N062E−S078N−G097S−S101Q−Q109G−N116L,G020K−N062E−M222S,G097S−S101Q−Q109G−S188D,G020K−S078N−L217E−S240R,G020K−N062E−S078N−G097A−S101N−Q109G−N116L−S188D,G020K−S024G−N062E−G097S−S101Q−Q109G−N116L−S188D,G020K−N062E−S078N−G097A−S101Q−N116L−S128A−M222S,G020K−N062E−S078N−S101N−N116L−S188D,G020K−S024G−N062E−S078N−S101G−N116L,G020K−N062E−S078N−S101N−N116L−S128A−S188D,G020K−S024G−N062E−G097S−S101N−Q109G−N116L−S128A−S188D−L217Q,G020K−N062E−G097S−S10
1N−Q109N−N116L,G020K−N062E−S101G−N116L−S188D−L217Q,G097A−S101N−S128A,S101G−Q109N−S128A−M222S,S024G−G097S−S101Q−Q109G−S188D−L217Q,G097S−S101Q−Q109N−S128A−S188D,S024G−S078N−G097A−S101Q−S188D−L217Q,S024G−S078N−S101G−Q109G−S128A−L217Q,G020K−N062E−S128L−S240R,N062E−S078N−S128L−S240R,N043R−G102A−S128L−L217E−S240R,N062E−S078N−L217E−S240R−E271L,S078N−S128Q−L217E−N269S,G020K−N062E−N123G−T213A,G020K−N062E−S078N−S099G−N116L−S128Q−T213A−L217N,G020K−N062E−S078N−S128I−L217N,G097A−S101Q−S128A−S188D−L217Q,G020K−N062E−S078N−G097S−S101N−Q109G−N116L,G020K−S024G−N062E−S078N−G097S−S101N−Q109G−N116L−S188D,G020K−N043R−S128L−S240R,S024G−S078N−G097A−S101N−Q109N−S128A,G020K−N062E−G097S−S101Q−N116L−L217Q,G020K−N062E−S078N−S128I,G020K−S024G−N062E−L090V−G097A−S101Q−N116L−M222S,G020K−N062E−S078N−S101Q−Q109G−N116L−S188D−L217Q,G020K−S024G−N062E−G097A−S101G−N116L−S128A−S188D−L217Q,G020K−N062E−G097S−S101N−Q109N−N116L−S188D−L217Q,G020K−S024G−A048V−N062E−S078N−G097A−S101N−N116L−S128A−L217Q,G020K−N062E−S078N−S101Q−Q109G−N116L,G020K−S024G−N062E−G097S−S101N−Q109N−N116L−S128A,G020K−N062E−S078N−G097A−S101Q−Q109G−N116L−S188D,G020K−N062E−S078N−G097A−S101N−Q109N−N116L−N218D,S024G−S101N−Q109G−S128A−S188D−M222S,S024G−G097A−S101Q−Q109N−S188D−L217Q,S024G−S078N−G097S−S101Q−Q109N−S128A−S188D,S101N−Q109G−M222S,S024G−I072V−G097S−S101N−S128A−L217Q,S101G−S128A,N043R−S078N−G102A−A215G,G020K−S101D−S128L−L217E−S240R,S078N−S101D−S128Q−L217E−S240R,G020K−N116L−S128L−M222S,G020K−N062E−S078N−N116L−T213A−M222S,G020K−N062E−S078N−N116L−S128Q,G020K−N062E−T213A,又はG020K−N062E−S078N−N116L−N123G−M222S(リスト15)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
118D−P129E−G159D−S188D−N248D−H249R,S024F−S078N−G118R−L217E,T022A−S024G−S078N−G097S−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−E271F−A272V,S024R−N062E−N116L−G118R−S128I−S188D,G118R−S128D−S166D−T213A,T022A−G097A−S101G−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−T033S−S101G−S103A−V104I−N116L−S128L−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S078N−S101Q−S103A−V104I−Q109G−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−G097S−S101N−S103A−V104I−Q109G−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−G097S−S101N−S103A−V104I−Q109N−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N076D−G097A−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−L126I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,G020R−S078G−G118S−S188D−H249R,T022A−S024G−N076D−S101Q−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101A−S103A,T022A−N076D−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D,S024R−S078D−G118D−S188D−N248D−H249R,S099A−V104I,T022A−G097S−S101Q−S103A−V104I−Q109N−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,S024R−S078G−G118D−G159D−N248D,T022A−S024G−S078N−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N076D−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−E271F,T022A−G097A−S101Q−S103A−V104I−L124V−S128A−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−G097A−S101Q−S103A−V104I−L124V−G159D−S188D−A232V−Q245R−N248D−E271F,S078G−G118D−P129E,S212W,T022A−S101G−S103A−V104I−I107V−P129E−G159D−S188D−A232V−N238Y−Q245R−N248D−A270V−E271F−A272V,T022A−S078N−S101Q−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−G097A−S101G−S103A−V104I−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,S101G−V104L,T022A−S101G−S103A−V104I−I107V−P129E−G159D−S188D−A232V−N238Y−Q245R−N248D−E271F,T022A−S024R−S101G−S103A−V104I−P129E−G159D−S188D−A232V−Q245R−N248D−E271F−A272V,T022A−S024G−G097A−S101Q−S103A−V104I−Q109N−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−N076D−S101G−S103A−V104I−P129E−A158E−S188D−A232V−Q245R−N248D−E271F−A272V,T022A−T033S−S101G−S103A−V104I−N116L−N117S−Y209A−G211Q−T213A−A232V,S101G−S103A−V104I−N116L−G118V−Y209A−G211Q−A232V,T022A−N062E−S101N−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−G097S−S101N−S103A−V104I−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,S024F−T213A,T022A−S024G−N076D−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,G020R−S024R−S078D−G118S−P129E−G159D−Q245R−H249R,T022A−N076D−S101Q−S103A−V104I−Q109G−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S078N−G097A−S099G−S101G−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N076D−S101G−S103A−V104I−G159D−S188D−L217Q−N218S−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−S101N−S103A−V104I−Q109G−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−S101N−S103A−V104I−Q109N−G159D−S188D−A232V−Q245R−N248D−E271F,G020R−S024R−S078D−G118D−Q245R,T022A−S078N−I079V−S101N−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024R−N116L−G118R−S128I−A158E−S166D,S078G−G118D−S188D,G097P−A098Q−S099G−G102A,S099A−S103G,S078D−G118D−P129E−Q245R−N248D,T022A−S024G−S078N−S101Q−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S078N−S101N−S103A−V104I−Q109G−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−N076D−S078N−G097S−S101Q−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024R−N116L−S128I−A158E−S166D−S188D,A016S−T022A−S101A−S103G−V104I,T022A−G097S−S101N−S103A−V104I−S128A−G159D−R186H−S188D−A232V−Q245R−N248D−E271F,T022A−G097A−S101Q−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S101N−S103A−V104I−L126I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101Q−S103A−V104I−L126I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N076D−G097S−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N043R−N076D−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−E271F−A272V,T022A−S024R−T033S−N062E−N116L−S128I−S188D,T022A−S024G−S078N−G097S−S101G−S103A−V104I−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022L−S078N−G118R−S128D−T213A,T022A−N076D−G097A−A098T−S101Q−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−S078N−G097A−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,S103A−V104L,G020R−S024R−S078D−G118D−P129E−Q245R−H249R,S024R−S078G−G118D−P129E−G159D−S188D−N248D,T022A−S024R−N043R−S101G−S103A−V104I−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−G061W−N076D−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−E271F,G020R−N062E−S078D−G118S−S188D−N248D,T022A−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−E271F,G100S−V104I,T022A−S024G−N076D−S078N−G097S−S101N−S103A−V104I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,G097P−A098F−S103A,T022A−G097S−S101Q−S103A−V104I−Q109G−G159D−S188D−A232V−Q245R−N248D−E271F,S024F−S078N−G118R−S128D−L217E,T022A−S101Q−S103A−V104I−Q109G−S128A−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,S024R−T033S−N116L−S128I−A158E−S166D,T022L−S024F−S128D,T022A−S101G−S103A−V104L,T022A−N043R−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−E271F−A272V,T022A−N076D−S101G−S103A−V104I−I107V−G159D−S188D−A232V−Q245
R−N248D−E271F,T022L−S024F−S078N,T022A−N062E−A158E−S188D,G020K−T022L−S166D−T213A,T022A−S024G−T071A−S078N−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,A016S−T022A−S101G−S103A−V104I−L148I,S078D−G118S−S188D−Q245R−N248D−H249R,G020K−T022L−S128D−S166D,T022A−S024G−N076D−G097S−S101N−S103A−V104I−Q109N−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N062E−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−E271F,G020R−N062E−S078G−G118D−P129E−Q245R−H249R,G020R−S078G−G118D−P129E−S188D−N248D,G020K−T022L−S024F−S078N−G118R−S128D−S166D,T022A−N076D−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−E271F,T022A−S101Q−S103A−V104I−L126I−P129E−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T255G,T022A−G097A−S101N−S103A−V104I−L126I−S128A−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−N076D−S101G−S103A−V104I−P129E−G159D−S188D−A232V−N238Y−Q245R−N248D−E271F,S024R−T033S−N062E−G118R−S166D−S188D,T022A−G097A−S101Q−S103A−V104I−S128A−P129S−G159D−S188D−A232V−Q245R−N248D−E271F,S024R−N062E−S078D−G118S−P129E−G159D−S188D−Q245R−H249R,T022A−S024G−S101Q−S103A−V104I−Q109N−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,A098Q−G102A,T022A−S024R−S101G−S103A−V104I−I107V−P129E−G159D−S188D−A232V−N238Y−Q245R−N248D−A270V−E271F,T022A−S024G−S078N−G097A−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−S078N−S101N−S103A−V104I−Q109G−G159D−S188D−A232V−Q245R−N248D−E271F,S024R−N116L,T022A−S101G−S103A−V104I−L126I−P129E−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,G020K−S078N−S128D,T022A−S024G−S101N−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−S078N−S101Q−S103A−V104I−S128A−G159D−S188D−T213A−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101N−S103A−V104I−L126I−P129E−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−G097A−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−S078N−G097A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,S024R−T033S−N062E−N116L−S166D,T022A−S024G−N076D−S101N−S103A−V104I−Q109G−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,A016S−S024F−S101G−S103A−V104I−N116L−Y209V−A232V,G020K−S024F−S078N−S128D−S166D,G025A,T022A−S024R−N076D−S101G−S103A−V104I−G159D−S188D−A232V−N238Y−Q245R−N248D−E271F,G097P−S099T−V104I,T022A−N076D−S078N−G097A−S101N−S103A−V104I−Q109G−G159D−S188D−A232V−Q245R−N248D−E271F,G020R−S024R−S078G−G118S−G159D−Q245R−N248D−H249R,T022A−S024G−S078N−S101Q−S103A−V104I−Q109G−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−G097A−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−N076D−S078N−G097S−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S078N−G097S−S101G−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S078N−G097S−S101Q−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,D041K,T022A−S024G−G097A−S101G−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024G−G097S−S101N−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,A016S−T022A−S101A−V104I−L111V−L148I,A016S−T022A−S101A−V104L−L111V,T022A−S024G−G097S−S101Q−S103A−V104I−Q109N−G159D−S188D−A232V−Q245R−N248D−E271F,S078G−G118S−S188D−N248D,G020K−T022L−S024F−S078N−S128D,G020K−T022L−S024F−G118R−S128D−T213A,T022A−S024G−G097S−S101N−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,S024F−S128D,T022A−N043R−N076D−S101G−S103A−V104I−A158E−G159E−S188D−A232V−Q245R−N248D−E271F,T022A−N076D−S101G−S103A−V104I−P129E−G159D−S188D−A232V−N238Y−Q245R−N248D−A270V−E271F−A272V,T022A−S101Q−S103A−V104I−L126I−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−P129E−G159D−S188D−A232V−N238Y−Q245R−N248D−A270V−E271F,T022A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−A270V−E271F−A272V−T274A,T022A−S101N−S103A−V104I−Q109G−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,G020K−T022L−N062E−S078D−G118S−N248D,T022A−S024R−N076D−S101G−S103A−V104I−I107V−G159D−S188D−A232V−N238Y−Q245R−N248D−A270V−E271F,A016S−T022A−S101G−S103A−V104I−N116A−Y209V−T213A−A232V,T022A−S101N−S103A−V104I−L126I−P129S−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−N076D−S078N−G097A−S101Q−S103A−V104I−Q109G−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−N062E−N116L,T033S−S101G−S103A−V104I−N116A−S128N−Y209A−T213A−A232V,T022A−S101N−S103A−V104I−L126I−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−S101G−S103A−V104I−I107V−G159D−S188D−A232V−Q245R−N248D−A270V−E271F,T022A−N043R−N076D−S101G−S103A−V104I−P129E−G159E−S188D−A232V−Q245R−N248D−E271F,G020R−S024R−S078D−G118D−P129E−G159D−N248D,T022A−S101G−S103A−V104I−L124V−S128A−P129E−G159D−S188D−L217Q−A232V−Q245R−N248D−E271F,T022A−S024G−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S024R−N076D−S101G−S103A−V104I−A232V−Q245R−A270V,T022A−S101G−S103A−V104I−P129E−S188D−A232V−Q245R−N248D−E271F−A272V,T022A−N076D−S078N−G097S−S101Q−S103A−V104I−S128A−G159D−S188D−A232V−Q245R−N248D−E271F,S099T,T022A−G097A−S101Q−S103A−V104I−L126I−P129E−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−G097A−S101G−S103A−V104I−G159D−S188D−A232V−Q245R−N248D−E271F,A098F−S099T−G102A,T022A−S101G−S103A−V104I−G159D−S188E−A232V−Q245T−N248D,D041L,S024R−N062E−S128I−A158E−S188D,N062E−S078D−G118D−N248D−H249R,G020K−S024F−G118R−T213A,S101G−S103G−V104I−S128N,S078N−G118R−S128D−T213A−L217E,T
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8N−S128Q−L217E,G020K−S078N−L217E−E271L,N062E−S078N−L217E,N062E−L217E,G020K−S078N−S101D−S128Q−L217E,G020K−S078N−S101D−S128L−S240R,G020K−N123G,G020K−S128Q−T213A−M222S,S078N−L217E,G020K−N062E−S128I−L217N,G020K−N062E−S078N−S128Q−L217N,G097S−S101N−Q109G−S128A−S188D−M222S,G020K−S024G−N062E−S101Q−Q109N−N116L−S188D,G020K−N062E−S078N−N116L−S128I−L217N,S024G−S078N−G097A−S101N−Q109G−S188D,S024G−G097A−S101Q−Q109N−L217Q,G020K−S101D−S128L,S101N−Q109G−S128A,S078N−S101D−L217E,S024G−S078N−S101N−S128A−M222S,G020K−S024G−N062E−G097A−S101Q−N116L−S128A−S188D,S024G−S078N−G097A−S101N−Q109N−S128A−M222S,G020K−N062E−S078N−G097A−S101N−N116L−S128A−S188D−L217Q,G020K−S024G−N062E−S078N−G097S−S101Q−N116L−S188D,G020K−N062E−S078N−G097S−S101G−N116L−M222S,G020K−S024G−N062E−S078N−S101N−N116L−M222S,G020K−S024G−N062E−G097S−S101Q−N116L,G020K−S024G−N062E−S101Q−Q109G−N116L−S128A−S188D,G020K−S024G−N062E−G097S−S101N−Q109N−N116L−S128A−S188D−L217Q,G020K−N062E−S078N−G097S−S101N−N116L,S024G−S078N−S101G−Q109G−M222S,S078N−G097A−S101G−Q109G−S128A,S078N−G097S−S101N−Q109N−S128A,S078N−G097A−S101N−Q109N−S188D,S024G−S101N−S128A−S188D−M222S,S101Q−Q109N−S188D−M222S,S101D−G102A−L217E,G020K−N062E−S078N−S101D−L217E,G020K−S078N−S101D−I107T−S128L−S240R,G020K−S078N−G100S−L217E−N218D,G020K−N043R−S101D,N043R−G100S−S128L−L217E,G020K−S078N−S101D−S128L−L217E−E271L,G020K−S101D−S128L−E271L,G020K−S101D−N116L−S128L−T213A,G020K−N062E−S078N−T213A−L217N,G020K−N062E−N116L−L217N,G020K−N062E−S128I−T213A,N062E−S101D−S128L−S240R,G097S−S101N−S128A,G020K−N062E−S078N−N116L−T213A−L217N,G020K−S101D−M222S,S024G−S101G−Q109G,G097A−S101Q−Q109G,G097S−S101Q−Q109N−S188D,G020K−N062E−G097S−S101N−N116L−S128A−S188D−L217Q,S078N−S101Q−S128A−M222S,S078N−G097A−S101Q−Q109N,S024G−S078N−G097A−S101Q−S128A−S188D,S078N−S101D−G102A,G020K−N062E−S078N−G097S−S101Q−Q109G−N116L−S128A−S188D−M222S,G020K−S024G−N062E−S078N−G097S−S101N−Q109N−N116L−S188D−L217Q−M222S,G020K−N062E−G097S−S101Q−N116L−S128A,G020K−S024G−N062E−G097S−S101Q−N116L−S128A−S188D−L217Q,S024G−S101N−Q109N−S128A,S024G−G097S−S101Q−S128A−S188D,S024G−S101Q−L217Q,G097S−S101G−S128A,S024G−S078N−S101Q−S128A−L217Q,S024G−S078N−G097S−S101N−S188D,S024G−G097A−S101N−S128A−M222S,G097A−S101Q−Q109N−S188D−M222S,S024G−S078N−G097S−S101Q,G020K−S101D−S128L−S212P−L217E−S240R,G020K−S101D−S128L−L217E−N218S−S240R,S101D−S128Q,G020K−N062E−S078N−E271L,S101D−E271L,S101D−S240R−E271L,G020K−S101D−E271L,G020K−N116L−S128L−T213A−M222S,G020K−N116L−S128Q−M222S,G020K−N062E−V084A−S128Q−M222S,G020K−N062E−S078N−N116L,S078N−S101N−Q109G−S128A−M222S,S024G−G097S−S101Q−Q109G,G020K−N062E−T213A−L217N,G097S−S101G−S128A−S188D,G020K−S240R,N062E−S078N,G020K−S128Q−M222S,S078N−G097S−S101G−Q109G,G020R−S024G−N043R−S078N−S101Q,G097S−S101N−Q109G−S128A−M222S,S024G−G097S−S101G−Q109N,S024G−S078N−G097A−S101G−Q109N,G020K−N062E−S078N−S101N−N116L−S128A−S188D−L217Q,G020K−N062E−S101Q−Q109G−N116L−S128A−M222S,G020K−S024G−N062E−S101Q−Q109N−N116L,S024G−S078N−S101Q−M222S,S024G−G097A−S101Q−Q109G−S128A,S101Q−Q109N−L217Q,S101Q−Q109G−S188D−L217Q,S024G−G097A−S101N−S188D−M222S,S024G−S078N−G097A−S101Q−Q109N,G097A−S101Q−S128A,G097A−S101Q−Q109G−S128A,S024G−G097S−S101Q−M222S,S078N−S101D−L217E−S240R,G020K−G100S−S128L,G020K−N043R−S078N−S128L−S240R,G020K−N043R−S101D−S240R,G020K−N043R−S078N−S128L,N062E−S128L,G020K−S078N−S101D−S128L,S078N−S101D,G020K−S101D−N116L−T213A−M222S,G020K−T213A−M222S,G020K−N116L−T213A,G020K−N116L,G020K−N062E−S128Q−L217N,S078N−G097S−S101G−Q109N−S128A,S078N−S101Q−Q109G,N062E−S078N−S128L,G020K−N062E−N116L−S128Q−T213A−L217N,G020K−N116L−T213A−M222S,G020K−S024G−N062E−S101Q−Q109H−N116L−M222S,G020K−N116L−S128Q−T213A−M222S,S024G−G097S−S101N,G020K−P055T−N062E−N116L−L217N,S024G−S101Q−S128A−S188D−M222S,G020K−M222S,G020K−N062E−S078N−G097A−S101N−N116L−S188D−L217Q,G097S−S101G−Q109N−M222S,G020K−S024G−N062E−S078N−G097A−S101N−N116L−S128A−L217Q−M222S,G020K−S024G−N062E−G097S−S101N−Q109N−N116L−S128A−S188D−L217Q−M222S,G020K−N062E−S078N−S101Q−N116L−S128A,S024G−S078N−S101N−Q109G−S188D−L217Q−M222S,S101N−Q109N−S128A−M222S,S101Q−Q109G−S128A−S188D,G097A−S101G−S188D−M222S,S078N−G097S−S101N−Q109G−S128A−S188D−L217Q−M222S,S024G−G097A−S101Q−M222S,S024G−G097S−S101N−Q109N−S128A−M222S,S024G−S078N−G097S−S101N−M222S,G020K−G102A−S240R,S078N−S128Q−E271L,G020K−N062E−S078N−S128Q,G020K−N062E−S078N−T213A−M222S,G020K−N062E−S078N−S128I−T213A−L217N,S078N−G097A−S101N,G020K−N062E−N116L−S128I−T213A−L217N,S024G−G097A−S101Q−S128A−S188D−M222S,S024G−S078N−G097A−S101N,S024G−S078N−G097S−S101G−M222S,G020K−N062E−S078N−N116L−S128Q−T213A−M222S,G020K−N062E−S128Q−M222S,G020K−N062E−S101Q−N116L,G020K−N062E−S101Q−Q109G−N116L−S188D−L217Q,G020K−S024G−N062E−G097A−S101N−N116L−S128A−S188D,G020K−S024G−N062E−S078N−S101Q−Q109G−N116L−S188D−M222S,S078N−G097S−S101N−Q109G−S128A−L217Q−M222S,S024G−S078N−S101N−Q109G−S128A−L217Q−M222S,G097A−S101Q−S128A−S188D,S024G−S078N−G097A−S101N−Q109N−S128A−S188D−L217Q−M222S,S024G−S078N−G097A−S101G−L217E−M222S,S078N−G097S−S101Q−Q109G−T274I,G097A−S101G−M222S,S101N−Q109N,G020K−L217E−S240R−E271L,S128Q−S240R−E271L,G020K−S101D−N116L−S128Q−M222S,G020K−P055L−N062E−N116L−S128I,G020K−N062E−S101G−N116L−S128A−M222S,G020K−S078N−S101D−S128L−S240R−E271L,G020K−N062E−S078N−G097S−S101Q−Q109N−N116L−
L217Q−M222S,S078N−S101D−S240R−E271L,S024G−S078N−S101N−Q109G−L217Q−M222S,G097A−S101G−Q109G−L217Q−M222S,G020K−S024G−N062E−S078N−G097S−S101N−N116L−S128A−L217Q−M222S,G020K−S078N−S128L−E271L,G020K−N062E−S078N−N116L−L217N,G097A−S101G−Q109G−S188D−L217Q−M222S,S024G−S078N−G097S−S101N−Q109G−S128A,G020K−S024G−N062E−S078N−G097S−S101N−N116L−S188D−M222S,G020K−S024G−N062E−G097S−S101Q−N116L−S128A−M222S,G020K−N062E−S078N−G097A−S101G−Q109G−N116L−S128A−S188D−L217Q,G020K−N062E−S101G−N116L−S128A−L217Q−M222S,S024G−G097A−S101Q−S188D−M222S,S024G−S101G,I072V−S101Q−S128A,
S078N−G097S−S101N−Q109N,S024G−G097A−S101N−Q109N−S188D−L217Q−M222S,S078N−S101Q−Q109N−S188D−L217Q−M222S,G020K−N043R−N062E−S128L−L217E,N043R−G102A−S128L−S240R,G020K−N116L−N123G−T213A−M222S,G020K−S101D−S128Q−T213A−M222S,S024G−G097A−S101Q−Q109G,G020K−S078N,G020K−N062E−S101Q−N116L−S188D,G020K−N062E−S078N−G097S−S101N−Q109G−N116L−S188D−L217Q−M222S,G020K−S024G−N062E−G097S−S101G−N116L−S128A−L217Q−M222S,G020K−N062E−G097A−S101N−N116L−S128A−L217Q−M222S,S078N−G097S−S101G−Q109N−M222S,S024G−G097A−S101Q−Q109N,S024G−G097S−S101N−Q109N−S128A−S188D−L217Q−M222S,S078N−S101N−Q109N−S188D−L217Q−M222S,S078N−S101D−S128L−L217E−S240R,G020K−N062E−S101D−N116L−S128L,G097S−S101N−S188D−M222S,G020K−S078N−S128L−S240R−E271L,G020K−N062E−N116L−S128I−T213A,G020K−S024G−N062E−S078N−G097S−S101Q−N116L−S188D−M222S,G020K−N062E−S101Q−Q109G−N116L−L217Q−M222S,G020K−S024G−N062E−G097A−S101Q−N116L−L217Q−M222S,G020K−N062E−S078N−G097S−S101Q−N116L−S128A−S188D−M222S−A232T,G020K−S024G−N062E−S078N−G097S−S101Q−Q109N−N116L−S128A−L217Q−M222S,G020K−N062E−G097A−S101Q−N116L−S188D−M222S,S024G−S078N−G097S−S101N−Q109G−S128A−L217Q−M222S,S024G−G097A−S101Q−Q109N−S128A−S188D−L217Q−M222S,G020K−N043R,G020K−N043R−S078N−G102A−S128L,G097R−S101D,G020K−N062E−S078N−I107V−N123G−S128I,G020K−N062E−S078N−N116L−N123G−T213A,G020K−N062E−N116L−S128I−M222S,G020K−N043R−S240R(リスト16)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
−S103A−V104I−L217Q−A232V−Q245R,T022A−S078N−G097S−S101G−S103A−V104I−L217Q−A232V−Q245R,G020R−S024R−N062E−S078G−G118S−Q245R,T022K−S101A−S103N−V104I−A232L−Q245R,G020R−T022W−S024R−R045T−S101A−P210I−T213A,G020R−S024R−S078G−G118S−S188D−Q245R,T022R−S101T−S103A−V104I−A232V−Q245W,T022R−S101N−S103A−V104I−A232V−Q245R,T022K−S101T−S103N−V104I−A232T−Q245R,T022A−S024G−S078N−S101Q−S103A−V104I−L217Q−A232V−Q245R,T022A−S078N−G097A−S101N−S103A−V104I−A232V−Q245R,T022Q−S101G−S103N−V104I−A232L−Q245R,T022A−S078N−G097A−S101Q−S103A−V104I−Q109N−A232V−Q245R,T022Q−S101G−S103A−V104L−A232V−Q245R,T022A−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−T022W−N043R−R045T−S101A−P210I,T022R−S101N−S103N−V104I−A232T−Q245R,G020R−N043R−R045T−S101A−N116L−G211Q−T213A,T022Q−S101A−S103N−V104I−A232V−Q245R,T022W−S024R−N043R−R045T−S101A−N116L−P210I,T022A−S078N−G097S−S101N−S103A−V104I−L217Q−A232V−Q245R,G020R−S078D−G118D−Q245R−H249R,G020R−S024R−N043R−S101A−P210I−G211Q−T213A,T022R−S101G−S103N−V104I−A232V−Q245W,T022A−S101T−S103N−V104L−A232L−Q245R,T022A−S024G−S078N−G097S−S101N−S103A−V104I−S128A−L217Q−A232V−Q245R,T022R−S101T−S103N−V104I−A232T−Q245R,G020R−N043R−S101A−P210I−T213A,G020R−S024R−N043R−S101A−N116L−G211Q−T213A,S024R−N043R−R045T−S101A−N116L−P210I−G211Q,T022A−S024G−G097S−S101N−S103A−V104I−L217Q−A232V−Q245R,E271R,T022K−S101T−S103G−V104I−A232V−Q245R,N043R−S101A−P210I−G211Q,G020R−S024R−S078G−G118S−P129E−G159D−Q245R,T022R−S101T−S103A−V104I−A232T−Q245S,E271W,S024R−N043R−R045T−S101A−N116L−P210I−T213A,T022A−S024G−S078N−S101N−S103A−V104I−A232V−Q245R,T022A−E089G−G097A−S101N−S103A−V104I−S128A−A232V−Q245R,T022R−S101T−S103A−V104I−A232L−Q245R,T022R−S101G−S103N−V104I−A232T−Q245S,T022A−S101G−S103A−V104I−A232M−Q245R,G020R−T022W−S024R−S101A−T213A,G020R−T022W−S024R−R045T−S101A−P210I,G020R−T022W−S024R−N043R−S101A−T213A,T022A−S024G−G097S−S101G−S103A−V104I−L217Q−A232V−Q245R,T022A−S024G−S078N−G097S−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S101A−T213A,E271S,G020R−S078G−G118S−Q245R−N248D−H249R,N043K,T022A−S101G−S103N−V104I−A232V−Q245R,T022Q−S101A−S103A−V104I−A232L−Q245R,G020R−T022W−S024R−R045T−S101A−T213A,G020R−S024R−S078G−G118S−Q245R−N248D−H249R,T022A−S024G−S078N−G097A−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,T022A−S024G−S078N−S101G−S103A−V104I−L217Q−A232V−Q245R,T022A−S024G−S101N−S103A−V104I−A232V−Q245R,G020R−T022W−S024R−S101A−N116L−P210I,G020R−T022W−N043R−R045T−S101A−T213A,T022A−S078N−G097A−S101N−S103A−V104I−L217Q−A232V−Q245R,T022A−S078N−S101N−S103A−V104I−L217Q−A232V−Q245R,T022R−S101N−S103G−V104L−A232V−Q245R,G020R−T022W−S024R−S101A−P210I−T213A,G020R−S024R−S078D−G118S−S188D−Q245R,G020R−S024R−S078D−G118S−G159D−Q245R,T022Y−S101T−S103A−V104I−A232M−Q245R,G020R−N043R−R045T−V051A−S101A−P210I−G211Q−T213A,G020R−T022W−S024R−N043R−R045T−S101A−T213A,T022A−S024G−S078N−G097S−S101G−S103A−V104I−L217Q−A232V−Q245R,T022A−S078N−S101Q−S103A−V104I−L217Q−A232V−Q245R,G020R−S024R−S101A−P210I−G211Q,T022Q−S101T−S103G−V104I−A232M−Q245R,G020R−N043R−S101A−G211Q−T213A,T022A−S101Q−S103A−V104I−P129S−L217Q−A232V−Q245R,T022A−S101T−S103N−V104I−A232V−Q245R,G020R−S024R−S078G−G118D−G159D−Q245R−N248D−H249R,G020R−T022W−R045T−S101A−P210I−G211Q,T022A−S078N−S101N−S103A−V104I−A232V−Q245R,T022R−S101T−S103N−V104I−S105G−A232V−Q245R,T022A−S024G−S078N−S101Q−S103A−V104I−A232V−Q245R,T022A−S101T−S103N−V104I−A232L−Q245R,T022Q−S101N−S103N−V104L−A232V−Q245R,T022R−S101N−S103N−V104L−A232M−Q245R,T022Q−S101G−S103N−V104I−A232T−Q245R,T022A−S101Q−S103A−V104I−L217Q−A232V−Q245R,T022Q−S101A−S103A−V104L−A232L−Q245R,G020R−N043R−R045T−S101A−G211Q−T213A,T022A−G097A−S101N−S103A−V104I−P129S−L217Q−A232V−Q245R,G020R−S024R−R045T−S101A−G211Q−T213A,T022A−S078N−G097A−S101G−S103A−V104I−S128A−A232V−Q245R,G020R−T022W−N043R−R045T−S101A−P210I−G211Q−T213A,T022R−S101N−S103N−V104I−A232L−Q245R,T022Y−S101G−S103A−V104I−A232M−Q245R,T022R−S101G−S103G−V104I−A232T−Q245R,T022A−S024G−S078N−G097S−S101N−S103A−V104I−L217Q−A232V−Q245R,G020R−S024R−S078G−G118D−N248D−H249R,T022A−S101A−S103N−V104L−A232V−Q245R,T022W−S024R−S101A−N116L−G211Q,G020R−S024R−S101A−T208A−P210I−G211Q,T022W−S024R−N043R−R045T−S101A−P210I−G211Q−T213A,T022Y−S101G−S103N−V104I−A232M−Q245R,T022R−S101T−S103A−V104L−A232T−Q245S,G020R−S024R−S078G−G118S−P129E−Q245R−N248D,T022A−S024G−S101Q−S103A−V104I−Q109N−A232V−Q245R,G020R−T022W−S101A,T022W−S024R−N043R−S101A−P210I−G211Q,G020R−S024R−N043R−S101A−P210I−G211Q,G020R−S024R−N062E−S078G−G118D−H249R,G020R−S024R−G047C−S101A−G211Q,G020R−S024R−S078D−G118D−P129E−Q245R−H249R,T022A−S101A−S103A−V104L−A232V−Q245R,T022A−S101T−S103N−V104L−A232M−Q245R,N018S−G020R−T022W−N043R−S101A−G211Q,T022Y−S101T−S103G−V104I−A232T−Q245R,T022K−S101A−S103A−V104I−A232M−Q245R,T022A−S024G−G097A−S101N−S103A−V104I−L217Q−A232V−Q245R,T022Y−S101N−S103N−V104L−A232V−Q245R,T022A−S101G−S103A−V104I−A232V−Q245R,T022A−G097A−S101G−S103A−V104I−P129S−A232V−Q245R,G020R−S078G−G118S−P129E−Q245R−H249R,T022A−G097S−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,T022Y−S101A−S103G−V104I−A232M−Q245R,S024R−S101A−G211Q,T022A−S024G−G097A−S101Q−S103A−V104I−Q109G−A232V−Q245R,T022A−S024G−S101G−S103A−V104I−S128A−A232V−Q245R,R045T−S101A−I107V−Q109R−P210I−G211Q−T213A,T022A−G097S−S101Q−S103A−V104I−L217Q−A232V−Q245R,T022K−S101T−S103A−V104I−A232T−Q245R,Q0
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128A,G020R−S024R−S078N−S101Q−Q109N−N116L−L217Q,T022R−S024G−S078N−S101N−S103A−V104I−N116L−S128A−A232V−Q245R,G020R−N043R−S1
01G−Q109N−N116L−S128A−L217Q,T022R−S101N−S103A−V104I−L217Q−A232V−Q245R,T022R−G097A−S101N−S103A−V104I−N116L−S128A−A232V−Q245R,G020R−S024R−G097A−S101A−S128A−L217Q,T022R−S024G−S078N−G097A−S101N−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S024R−S078N−G097S−S101N−Q109G−N116L−S128A−L217Q,T022R−S024G−S101G−S103A−V104I−N116L−L217Q−A232V−Q245R,T022R−G097A−S101Q−S103A−V104I−N116L−S128A−A232V−Q245R,G020R−N043R−S101Q−S128A−L217Q,G020R−S024R−S078N−S101N−Q109G−S128A−L217Q,G020R−S024R−S078N−G097A−S101N−Q109N−N116L−S128A−L217Q,T022R−S024G−G097A−S101Q−S103A−V104I−N116L−L217Q−A232V−Q245R,G020R−S024R−S078N−G097S−S101G−S128A−N204S−L217Q,T022R−S024G−S078N−S101Q−S103A−V104I−N116L−S128A−A232V−Q245R,G020R−S024R−S078N−G097S−S101Q−Q109N−N116L−L217Q,G020R−S024R−S078N−S099G−S101Q−Q109N−N116L−L217Q,T022R−S024G−G097A−S101G−S103A−V104I−Q109G−N116L−L217Q−A232V−Q245R,T022R−S078N−G097A−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,T022R−G097A−S101G−S103A−V104I−Q109G−N116L−L217Q−A232V−Q245R,G020R−S024R−G097A−S101N−Q109N−S128A−L217Q,T022R−G097S−S101N−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S024R−K094R−S101N−N116L−S128A−L217Q,T022R−S024G−S078N−G097A−S101G−S103A−V104I−N116L−S128A−L217Q−A232V−Q245R,G020R−S024R−G097A−S101A−N116L−S128A−L217Q,G020R−S024R−S078N−G097W−S101Q−Q109N−N116L−L217Q,T022R−G097S−S101N−S103A−V104I−N116L−S128A−L217Q−A232V−Q245R,T022R−S101Q−S103A−V104I−N116L−L217Q−A232V−Q245R,T022R−S024G−S078N−G097A−S101Q−S103A−V104I−N116L−S128A−L217Q−A232V−Q245R,T022R−S078N−G097A−S101Q−S103A−V104I−Q109N−N116L−S128A−L217Q−A232V−Q245R,G020R−N043R−G097S−S101Q−Q109G−N116L−S128A−L217Q,T022R−S024G−G097A−S101G−S103A−V104I−N116L−S128A−L217Q−A232V−Q245R,T022R−G097S−S101G−S103A−V104I−L217Q−A232V−Q245R,T022R−S024G−G097A−S101Q−S103A−V104I−Q109G−N116L−L217Q−A232V−Q245R,T022R−S024G−S078N−G097A−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,T022R−S101Q−S103A−V104I−Q109G−N116L−S128A−L217Q−A232V−Q245R,T022R−S078N−G097S−S101G−S103A−V104I−N116L−S128A−L217Q−A232V−Q245R,T022R−S024G−T071A−S078N−S101N−S103A−V104I−Q109N−N116L−S128A−A232V−Q245R,T022R−S024G−G097A−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,T022R−S101G−S103A−V104I−Q109N−S128A−A232V−Q245R,T022R−S024G−G097S−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,T022R−S024G−S078N−S101Q−S103A−V104I−Q109N−N116L−S128A−L217Q−A232V−Q245R,T022R−S101G−S103A−A232V−Q245R,T022R−S101G−S103A−V104I−A232V−Q245R−E271A,T022R−S103A−V104I−A232V−Q245R,T022R−S101G−V104I−A232V−Q245R,T022R−S101G−S103A−V104I−Q245R,G020R−N043R−E271A,G020R−S024R−I035T−S101A−N116L,G020R−N043R−P239G,G020R−N043R−S242L,又はG020R−N043R−V234F(リスト17)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
−S101A−G211Q−T213A,T022Y−S101N−S103N−V104L−A232L−Q245R,T255G,T022A−G097S−S101N−S103A−V104I−S128A−A232V−Q245R,T022W−S024R−N043R−S101A−P210I−T213A,N269K,T022R−S101T−S103A−V104I−A232L−Q245S,T022A−S024G−I072V−S078N−G097S−S101N−S103A−V104I−S128A−A232V−Q245R,T022K−S101T−S103G−V104I−A232M−Q245R,H017R−N043R−R045T−S101A−P210I−T213A,T022A−S024G−G097S−S101G−S103A−V104I−S128A−A232V−Q245R,T022A−S078N−G097A−S101Q−S103A−V104I−A232V−Q245R,T022A−N076D−G097A−S101N−S103A−V104I−A232V−Q245R,T022A−S024G−V026A−S101G−S103A−V104I−S128A−A232V−Q245R,T022A−S024G−G097A−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,T022Q−S101T−S103G−V104I−A232L−Q245R,T022W−S024R−S101A−P210I−G211Q−T213A,T022Q−S101N−S103A−V104I−A232M−Q245R,G020R−R045T−S101A,T022Y−S101N−S103N−V104I−A232V−Q245R,T022R−S101G−S103A−V104I−A232L−Q245R,S024R−S078D−G118D−P129E−Q245R−H249R,T022R−S101A−S103A−V104I−A232M−Q245S,G020R−S101A−P210I−G211Q,T022W−N043R−R045T−S101A−P210I−G211Q,T022R−S101G−S103A−V104I−A232M−Q245S,T022A−S024G−N076D−S101G−S103A−V104I−L217Q−A232V−Q245R,T022R−S101T−S103N−V104I−A232V−Q245S,T022Q−S101G−S103N−V104L−A232M−Q245R,T022K−T038I−S101G−S103A−V104I−A232T−Q245S,N043R−R045T−S101A−P210I−G211Q,T022K−S101T−S103A−V104L−A232M−Q245R,T022Y−S101T−S103N−V104I−A232T−Q245R,G020R−S024R−N043R−S101A−P210I−T213A,S099G−S101G,T022A−S101N−S103N−V104L−A232T−Q245R,T022A−S024G−N076D−S078N−G097A−S101N−S103A−V104I−A232V−Q245R,T022R−S101N−S103A−V104I−A232V−Q245W,T022W−N043R−R045T−S101A−P210I,T022K−S101A−S103G−V104I−A232T−Q245R,T022Q−S101N−S103A−V104I−A232T−Q245S,T022A−S101Q−S103A−V104I−Q109G−A232V−Q245R,T022A−G097A−S101Q−S103A−V104I−S128A−P129S−L217Q−A232V−Q245R,T022A−S078N−G097A−S101Q−S103A−V104I−L217Q−A232V−Q245R,S024R−S078G−G118S−G159D−Q245R,T022K−S101N−S103N−V104I−A232T−Q245R,A098F−S099A−V104I,G020R−R045T−S101A−G211Q−T213A,T022A−N076D−S078N−G097A−S101G−S103A−V104I−A232V−Q245R,S024R−S078D−G118S−G159D−Q245R,T022A−S024G−N076D−S101N−S103A−V104I−Q109N−A232V−Q245R,T022K−S101T−S103N−V104I−A232M−Q245R,T022A−S024G−S078N−G097S−S101N−S103A−V104I−S128A−A232V−Q245R,T022Q−S101T−S103N−V104I−A232L−Q245S,A114T,T022Q−S101N−S103N−V104L−A232T−Q245R,T022A−S078N−S101G−S103A−V104I−Q109N−A232V−Q245R,T022K−S101T−S103A−V104I−A232M−Q245R,T022A−S024G−G097S−S101Q−S103A−V104I−Q109G−S128A−L217Q−A232V−Q245R,T022A−S101G−S103A−V104I−N116L−Y209V−G211Q−A232V,T022A−S101T−S103N−V104I−A232M−Q245W,G020R−T022W−S024R−S101A−N116L−G211Q,T022A−S078N−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−R045T−S101A−G211Q,T022A−N076D−S078N−G097A−S101G−S103A−V104I−S128A−A232V−Q245R,S024R−S101A−T213A,T022A−S078N−S101G−S103A−V104I−A232V−Q245R,G020R−S024R−S078D−G118S−G159D−S188D−Q245R−N248D−H249R,T022Y−S101N−S103N−V104I−A232V−Q245W,T022Y−S101A−S103G−V104I−A232V−Q245R,T022A−S024R−N076D−S101G−S103A−V104I−A232V−N238Y−Q245R,G020R−S078G−G118S−G159D−H249R,T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−A272V,T022R−S101N−S103A−V104I−A232V−Q245S,G020R−S101A−P210I−G211Q−T213A,G020R−S024R−S078D−G118S−G159D−S188D−Q245R,S087R,G020R−S024R−R045T−A048T−S101A−G211Q,T022A−S024G−G097S−S101Q−S103A−V104I−A232V−Q245R,G020R−S024R−S078G−G118S−P129E−S188D−Q245R−N248D−H249R,T022A−G097S−S101G−S103A−V104I−Q109N−A232V−Q245R,L021S−T022A−S024G−N076D−S078N−S101G−S103A−V104I−S128A−A232V−Q245R,S242K,T022K−S101A−S103A−V104I−A232V−Q245R,T022K−S101N−S103A−V104L−A232L−Q245R,T022A−N076D−S101G−S103A−V104I−A232V−N238Y−Q245R−A270V−A272V,T022R−S101T−S103A−V104I−A232V−Q245S,T022Y−S101N−S103G−V104I−A232L−Q245R,T022Q−S101N−S103G−V104I−A232V−Q245R,T022A−S101G−S103A−V104I−A232V−Q245W,T022R−S101A−S103A−V104I−A232L−Q245S,G020R−T022W−R045T−F050L−S101A−P210I−G211Q−T213A,T022A−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S101A−G211Q−T213A,T022A−N076D−S101G−S103A−V104I−A232V−Q245R−A272V,T022A−S101G−S103A−V104I−A232V−N238Y−Q245R−A270V,T022A−S101N−S103G−V104I−A232V−Q245R,G020R−S101A−T208P−P210I−G211Q,D181S,S101G−S103A−V104I−N116L−Y209V−A232V,T022Q−S101A−S103N−V104I−A232T−Q245R,T022A−S101G−S103N−V104L−G211S−A232T−Q245R,T022A−G097A−S101Q−S103A−V104I−L217Q−A232V−Q245R,T022A−S101T−S103N−V104I−A232M−Q245S,T022A−S101G−S103A−V104I−Q109N−A232V−Q245R,T022Q−S101A−S103G−V104I−A232M−Q245R,G020R−S078G−G118S−G159D−N248D−H249R,T022A−N076D−S101N−S103A−V104I−A232V−Q245R,T022A−S024G−G097S−S101N−S103A−V104I−Q109G−S128A−A232V−Q245R,T022Q−S101A−S103A−V104I−A232T−Q245R,T022A−S101G−S103A−V104I−A232L−Q245R,T022A−S101G−S103A−V104I−P129E−A232V−N238Y−V244I−Q245R−A270V−A272V,G020R−S024R−S078D−G118D−G159D−Q245R−N248D−H249R,T022R−S101A−S103N−V104I−A232V−Q245W,T022Q−S101A−S103N−V104I−A232M−Q245R,T022Q−S101A−S103N−V104L−A232L−Q245R,T022A−S024G−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,T022Q−S101G−S103G−V104I−A232M−Q245R,G020R−S078G−G118S−G159D−Q245R−H249R,T022R−S101A−S103N−V104L−A232V−Q245S,T022A−S024V−G097S−S101N−S103A−V104I−H120N−S128A−A232V−Q245R,T022A−A073V−N076D−S078N−S101N−S103A−V104I−A232V−Q245R,T022Q−S101G−S103N−V104L−A232V−Q245R−T274I,T022A−S101N−S103N−V104I−A232T−Q245R,T022W−S024R−R045P−S101A−P210I−G211Q−T213A,G020R−S024R−N062E−S078G−G118D−Q245R−N248D,T022Q−S101A−S103N−V104L−A232M−Q245R,T022Q−S101T−S103G−V104L−A232T−Q245R,T022R−S101G−S103N−A232L−Q245R,T022A−G097S−S101Q−S103A−V104I−Q109N−L217Q−A232V−Q245R,T022A−S024G−G097A−S101Q−S1
03A−V104I−S128A−L217Q−A232V−Q245R,S024R−S101A−G211Q−T213A,T022R−S101N−S103N−V104L−A232T−Q245S,G020R−R045T−S101A−P210I,T022R−S101A−S103A−V104I−A232M−Q245W,T022A−S101N−S103N−V104I−A232L−Q245R,T022A−S101G−S103G−V104I−A232M−Q245R,G020R−S024R−S078D−G118S−S188D−Q245R−N248D,S099T−S103G,T022W−N043R−S101A−P210I,T022W−A029V−N043R−S101A−P210I,F050R,T022A−S024G−N076D−S078N−G097S−S101Q−S103A−V104I−Q109N−A232V−Q245R,T022A−S024G−N076D−S101G−S103A−V104I−A232V−Q245R,T022R−S101G−S103N−V104L−A232L−Q245R,T022A−S101N−S103A−V104I−Q109N−S128A−A232V−Q245R,S024R−R045T−S101A,T022A−N076D−G097S−S101N−S103A−V104I−L217Q−A232V−Q245R,T022Q−S101G−S103A−V104I−A232M−Q245S,T022W−S024R−N043R−R045T−S101A−G211Q−T213A,G020R−S078G−G118S,T022W−N043R−G046C−S101A−P210I−G211Q,S101A−G211Q−T213A,T022A−N076D−S078N−S101G−S103A−V104I−A232V−Q245R,T022A−S024G−N076D−G097S−S101Q−S103A−V104I−A232V−Q245R,T022A−S101N−S103A−V104I−L126I−P129S−A232V−Q245R,T022R−S101T−S103N−V104I−A232L−Q245W,T022A−S101G−S103A−V104I−A232V−N238Y−Q245R−A270V−A272V,S078G−G118D−Q245R,T022A−S024R−S101G−S103A−V104I−P129E−A232V−N238Y−Q245R−A270V,
T022A−N076D−G097S−S101N−S103A−V104I−Q109G−S128A−A232V−Q245R,T022W−S024R−R045T−S101A−N116L−P210I−T213A,T022R−S101T−S103N−V104I−A232L−Q245S,T022W−S024R−N043R−R045T−S101A−S106L−P210I−G211Q,T022A−E089G−G097A−S101Q−S103A−V104I−P129S−L217Q−A232V−Q245R,T022A−S101A−S103G−V104I−A232L−Q245S,N043R−S101A−P210I−T213A,N043R−R045T−S101A−T213A,S078G−G118D−H120N−H249R,T022Q−S101T−S103N−V104I−A232L−Q245R−R275H,T022Y−S101A−S103A−V104I−A232T−Q245S,T022K−S101N−S103N−V104I−A232M−Q245R,T022R−S101T−S103N−V104L−A232V−Q245S,T022A−N076D−G097S−S101N−S103A−V104I−A232V−Q245R,M119L,A098F−S099A−S101G−V104I,S078D−G118S−Q245R,T022Y−S101N−S103A−V104I−A232L−Q245S,T022A−G097A−S101N−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S078G−G118D−N248D−H249R,T022R−S101A−S103N−V104I−A232T−Q245S,T022R−S101G−S103N−V104I−A232L−Q245S,S024R−S078D−G118D−S188D−Q245R−H249R,S132H,A098Q−S099G−S101G−V104L,N043R−S101A−P210I−G211Q−T213A,T022Q−S101G−S103A−V104I−A232M−Q245W,T022A−S101Q−S103A−V104I−L126I−P129S−A232V−Q245R,T022K−S101T−S103G−V104I−A232M−Q245S,T022W−N043R−R045T−S101A−G211Q−T213A,T022Q−S101N−S103G−V104I−A232V−Q245W,D181T,G020R−S024R−S078D−G118S−P129E−G159D−Q245R−H249R,G020R−S024R−S078G−G118D−G159D−S188D−Q245R,T022A−S101T−S103N−V104L−A232L−Q245S,T022A−S101G−S103N−V104L−A232V−Q245S,T022A−S024G−G097A−S101N−S103A−V104I−S128A−L217Q−A232V−Q245R,T022A−S024G−N076D−S101N−S103A−V104I−S128A−A232V−Q245R,T022Y−S101T−S103A−V104L−A232M−Q245R,T022Q−S101T−S103N−V104L−A232T−Q245R,F050S,T022Y−S101G−S103N−V104I−A232V−Q245R,G020R−R045T−S101A−T213A,T022K−S101N−S103G−V104I−A232V−Q245W,S024R−S078G−G118D−P129E−G159D−Q245R−H249R,T022Q−S101T−S103N−V104I−A232M−Q245W,S049W,T022A−S101A−S103N−V104L−A232L−Q245R,T022A−N076D−S101G−S103A−V104I−I107V−P129G−A232V−Q245R−A270V,S099A−V104I,T022Q−S101A−S103G−V104I−A232V−Q245W,T022A−N076D−S101G−S103A−V104I−A232V−N238Y−Q245R,T022A−S101G−S103A−V104I−L124V−L217Q−A232V−Q245R,T022R−G097S−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,T022R−G097A−S101Q−S103A−V104I−Q109N−S128A−A232V−Q245R,R010A−T022R−S024F−S101G−S103A−V104I−A232V−Q245R−L267N−E271H,G020R−S024G−N043R−S078N−S101G−Q109N−N116L−L217Q−M222S,G020R−N043R−E271H,G020R−N043R−E271I,G020R−S024R−S101A−N116L−N269I,T022R−S101G−S103A−V104I−A232V−Q245R−E271F,G020R−N043R−E271F,G020R−N043R−N269I,G020R−S024R−S101A−N116L−E271H,T022R−S101G−S103A−V104I−A232V−Q245R−E271H,G020R−I035T−N043R,G020R−S024R−S101A−A114T−N116L,G020R−S024R−S101A−N116L−E271I,G020R−N043R−A114T,G020R−N043R−L267N,G020R−S024R−S101A−N116L−L267N,G020R−S024R−V028A−S101A−N116L,G020R−S024R−S101A−N116L−G258R,G020R−N043R−G258R,G020R−S024R−S101A−N116L−S242L,G020R−S024R−S101A−N116L−P239G,I008N−G020R−S024R−S101A−N116L,G020R−S024R−S101A−N116L−V234F,T022R−S101G−S103A−V104I−A232V,G020R−S024R−S101A−N116L−E271A,R010A−G020R−N043R,G020R−S024R−S101A−N116L−E271F,G020R−V028A−N043R,I008N−G020R−N043R,又はG020R−S024F−S101A−N116L(リスト18)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
T022Q−S101T−S103N−V104I−A232V−Q245S,T022A−S024F−S101G−S103A−V104I−N116L−Y209V−T213A−A232V,T022A−S101N−S103G−V104L−A232T−Q245R,T022A−S024R−S101G−S103A−V104I−P129E−A232V−N238Y−Q245R,T022A−N076D−G097S−S101Q−S103A−V104I−A232V−Q245R,T022A−N076D−S078N−G097A−S101N−S103A−V104I−A232V−Q245R,T022A−S101N−S103A−V104I−Q109G−S128A−A232V−Q245R,S259W,A016S−T022A−S024F−S101G−S103A−V104I−N116A−Y209V−G211Q−A232V,T022W−S101A−P210I−G211Q−T213A,T022A−S024G−N076D−G097S−S101N−S103A−V104I−A232V−Q245R,V028T−A215V,S024R−S078D−G118S−S188D−Q245R,T022Q−S101T−S103A−V104I−A232V−Q245W,T022A−S101N−S103A−V104I−Q109G−L217Q−A232V−Q245R,T022A−S024G−T071A−G097S−S101Q−S103A−V104I−S128A−A232V−Q245R,H120P,G020R−S024R−N062E−S078D−G118D−Q245R,T022A−N076D−S101Q−S103A−V104I−A232V−Q245R,T022Q−S101A−S103N−V104I−A232L−Q245W,T022Q−S101N−S103A−V104L−A232T−Q245R,T022W−S024R−N043R−R045T−S101A−N116L−P210I−G211Q,T022A−G097S−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S078G−G118S−G159D−S188D−H249R,A013S,A232N,T022A−N076D−S101G−S103A−V104I−A232V−Q245R,T022A−S024G−N076D−S078N−G097S−S101N−S103A−V104I−A232V−Q245R,I035T,
V051M,N123A,G020R−S078G−G118S−G159D−Q245R−N248D,T022Y−S101A−S103N−V104I−A232L−Q245W,T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R−A270V,G020R−S078D−G118S,T022R−S101N−S103N−V104L−A232M−Q245W,T022A−S024G−N076D−G097S−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,T022A−S101G−S103N−V104L−A232V−Q245R,T022A−N076D−G097A−S101Q−S103A−V104I−A232V−Q245R,T022A−S024R−N076D−S101G−S103A−V104I−I107V−P129E−A232V−Q245R,S024R−R045T−S101A−P210I−G211Q,T022A−S078N−S101N−S103A−V104I−Q109N−S128A−A232V−Q245R,T022A−S024G−S078N−G097A−S101N−S103A−V104I−Q109N−A232V−Q245R,G020R−S024R−S078G−G118D−P129E−G159D−H249R,G020R−S078G−G118D−P129E−S188D−Q245R−H249R,P014W,G020R−S024R−S078G−G118S−G159D−S188D−Q245R−N248D,T022R−S101G−S103N−V104I−A232M−Q245W,T022R−A098V−S101G−S103N−V104L−A232T−Q245R,T022A−S101T−S103A−V104I−A232V−Q245W,G020R−T022W−R045T−S101A−T213A,N043R−R045T−S101A,T022K−S101N−S103A−V104I−A232V−Q245R,T022K−S101T−S103N−V104I−A232L−Q245S,S056V,G020R−T022W−R045T−S101A−G211Q,G020R−S024R−S078D−G118D−Q245R−N248D,G020R−S024R−S078D−G118S−G159D−V244L−Q245R−N248D,T022A−G097A−S101Q−S103A−V104I−Q109G−S128A−A232V−Q245R,T022A−N076D−G097S−S101G−S103A−V104I−A232V−Q245R,G020R−T022W−R045T−S101A−N116L−P210I,T022Q−S101N−S103N−V104I−A232M−Q245S,T022Y−S101G−S103N−V104I−A232V−Q245W,A114V,S141C,T022A−N076D−S078N−S101N−S103A−V104I−A232V−Q245R,S056H,S078D−G118D−Q245R,S024R−N043R−R045T−S101A−T213A,T022Y−S101T−S103G−V104I−A232V−Q245S,T022A−S024G−G097S−S101Q−S103A−V104I−S128A−L217Q−A232V−Q245R,N269W,S078G−G118S−G159D−Q245R−N248D−H249R,T022W−S024R−R045T−S101A,T022A−S024R−S101G−S103A−V104I−P129E−A232V−N238Y−Q245R−A270V−A272V,T022A−S024R−S101G−S103A−V104I−P129E−A232V−Q245R,T022A−S024R−N076D−S101G−S103A−V104I−I107V−P129E−A232V−N238Y−Q245R−A270V−A272V,A122F,S024R−S078D−G118S−P129E−G159D−Q245R−H249R,S099G,T022K−S101T−S103G−V104I−A232V−Q245S,S009G−T022A−S078N−S101Q−S103A−V104I−Q109G−S128A−L217Q−A232V−Q245R,A098Q,T022A−S101N−S103A−V104L−A232L−Q245R,T022A−S101A−S103N−V104I−A232T−Q245W,T022A−S024G−N076D−G097A−S101N−S103A−V104I−A232V−Q245R,S024R−S078G−G118D−G159D−H249R,T022A−S024G−N076D−G097S−S101N−S103A−V104I−S128A−A232V−Q245R,T022A−S024G−N076D−S078N−S101Q−S103A−V104I−S128A−A232V−Q245R,T022A−S101Q−S103A−V104I−L124V−S128A−P129S−A232V−Q245R,T022R−S101N−S103A−V104I−A232M−W241R−Q245W,R045T−S101A−P210I−G211Q,G020R−S024R−S078G−G118S−P129E−Q245V−N248E,T022Q−S101T−S103N−V104I−A232L−Q245W,T022A−S024G−S078N−S101N−S103A−V104I−Q109G−L217Q−A232V−Q245R,T022A−S024G−G097A−S101N−S103A−V104I−L217Q−A223S−A232V−Q245R,T022K−S101T−S103A−V104I−A232T−Q245W,N043R−S101A−G211Q,T022A−S101G−S103A−V104I−Q109N−S128A−A232V−Q245R,T022A−G097A−S101G−S103A−V104I−S128A−L217Q−A232V−Q245R,G020R−S078G−G118S−P129E−H249R,S024R−S078G−G118S−G159D−S188D−Q245R,N043R−R045T−S101A−N204S−P210I−T213A,T022R−S101N−S103A−V104L−A232V−Q245S,T022R−S101N−S103G−V104I−A232V−Q245S,T022K−S101T−S103N−V104I−A232M−Q245S,T022A−N076D−S101N−S103A−V104I−L217Q−A232V−Q245R,T022A−S024G−N076D−S078N−S101N−S103A−V104I−Q109G−S128A−A232V−Q245R,G020R−T022W−R045T−S101A−P210I−T213A,T022A−N076D−G097A−S101G−S103A−V104I−L217Q−A232V−Q245R,T022W−S101A−P210I,T022A−G097A−S101N−S103A−V104I−L126I−P129S−A232V−Q245R,T022A−S078D−S101N−S103A−V104I−S128A−A232V−Q245R,Q236L,T022Y−S101T−S103N−V104I−A232V−Q245S,A200D,G020R−S078G−G118S−S188D−H249R,T022A−S101G−S103N−V104I−A232T−Q245W,T022A−S024G−N076D−G097A−S101N−S103A−V104I−S128A−A232V−Q245R,G157I,G020R−S024R−S078G−G118S−P129E−G159D−S188D−Q245R,T022R−S078N−G097S−S101G−S103A−V104I−Q109G−S128A−A232V−Q245R,R010A−G020R−S024R−S101A−N116L,G020R−N043R−M222S(リスト19)、サブチリシン変異体のアミノ酸位置は、配列番号1に示すバチルス・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。
本明細書に記載されているのは、単離された核酸、非天然の核酸、又は組み換え核酸(本明細書で「ポリヌクレオチド」とも呼ばれる)で、これは集合的に「本発明に使用されるポリペプチドをコードするための核酸」又は「本発明に使用されるポリペプチドをコードするためのポリヌクレオチド」と呼ばれることもあり、本発明に使用されるポリペプチドをコードする。本発明に使用されるポリペプチドをコードするための核酸は、以下に記載の全てのものを含めて、本発明に使用されるポリペプチドの組み換え体の産生(例えば発現)、典型的には、対象とするポリペプチドをコードしている配列又はそれらの断片を含むプラスミド発現ベクターの発現を介した産生に有用である。上述のように、ポリペプチドには、例えば、酵素活性(例えば、タンパク質分解活性)を有する、変異型サブチリシンのポリペプチドなどの変異型プロテアーゼのポリペプチドが包含され、プロテアーゼ変異体ポリペプチドは、クリーニング用途、及びクリーニングする必要のある物品又は表面(例えば、物品の表面)をクリーニングするためのクリーニング組成物に有用である。
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;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;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;及び/又は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;及び/又はe)試験方法7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15、1.1〜約10、又は更には1.1〜約7である。試験方法2、試験方法3、試験方法4、試験方法6、及び試験方法7は、以下の実施例1の表題「試験方法」の節で明記される。本明細書で引用される全ての変異は、図1に示されるようなBPN’番号付けスキームを利用する。一部の実施形態では、本明細書で参照される変異体は、BPN’番号付与スキームを用い配列番号2のアミノ酸配列と比較されるアミノ酸配列を有する変異体を指す。
「伝導度の低い洗濯洗剤溶液」は、約0.1mS/cm〜約3mS/cm、約0.3mS/cm〜約2.5mS/cm、又は更には約0.5mS/cm〜約2mS/cmの伝導度を有するものとして定義される。「伝導度の高い洗濯洗剤溶液」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の伝導度を有するものとして定義される。上記の実施例は非限定的なものであることが意図される。冷水性能を最適化するために変異が組み合わされる場合にも、酵素電荷は更なる位置における変異により均衡が得られ得る。
本発明の変異型プロテアーゼをコードする本発明に使用される改変ポリヌクレオチドを生成するのに好適な様々な方法が当該技術分野において既知であり、限定するものではないが、例えば、部分飽和変異導入、系統的変異導入、挿入変異導入、欠失変異導入、ランダム変異導入、部位特異的変異導入、及び定向進化、並びに様々な他の組み換え手法が挙げられる。改変されたポリヌクレオチド及びタンパク質(例えば、変異型プロテアーゼ)の製造方法としては、遺伝子の非相同組み換えに基づく方法、例えばITCHY(Ostermeier et al.,7:2139〜44[1999]を参照されたい)、SCRACHY(Lutz et al.98:11248〜53[2001]を参照されたい)、SHIPREC(Sieber et al.,19:456〜60[2001]を参照されたい)、及びNRR(Bittker et al.,20:1024〜9[2001];Bittker et al.,101:7011〜6[2004])を参照されたい、並びにランダムな及び標的とされる変異、欠失及び/又は挿入を組み込むためにオリゴヌクレオチドを使用することに基づく方法(Ness et al.,20:1251〜5[2002];Coco et al.,20:1246〜50[2002];Zha et al.,4:34〜9[2003];Glaser et al.,149:3903〜13[1992]を参照されたい)などのDNAシャフリング方法が挙げられる。
本明細書に記載されているのは、本明細書に記載の少なくとも1種の本発明のポリヌクレオチド(例えば、本明細書に記載の本発明の変異型プロテアーゼをコードするポリヌクレオチド)を含む単離された又は組み換えベクター、少なくとも1種の本発明の核酸又はポリヌクレオチドを含む単離された又は組み換えプロテアーゼ発現ベクター又は発現カセット、少なくとも1種の本発明の核酸又は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、少なくとも1種の本発明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、少なくとも1種の本発明のポリヌクレオチドを含む細胞を含む細胞培養物、少なくとも1種の本発明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を1種以上含む組成物である。
一部の実施形態では、本発明のプロテアーゼ変異体、より具体的にはサブチリシン変異体は、助剤とプロテアーゼ変異体とを含む組成物に使用することができ、ここで、組成物は布地ケア及びホームケア製品である。
一部の実施形態では、クリーニング及び/又は処理組成物を含む消費者製品は、少なくとも1つのプロテアーゼ変異体、特にサブチリシン変異体と少なくとも1つの助剤とを含む。一部の実施形態では、これらの助剤は、例えば、クリーニングされる基材を処理する際のクリーニング性能を補助又は強化させるために、あるいは香料、着色剤、又は染料などの場合にはクリーニング組成物の美観を改善するために組み込まれる。これらの助剤が本発明の変異型プロテアーゼに添加されることは理解されたい。このような追加的成分の正確な性質及びその添加濃度は、組成物の物理的形態、及び組成物が使用される洗浄操作の性質によって決まる。クリーニング及び/又は処理助剤は、これらに限定するものではないが、界面活性剤、ビルダー、漂白剤、漂白活性剤、漂白酵素、その他の酵素、酵素安定系、キレート剤、汚れ剥離ポリマー、染料移行剤、分散剤、抑泡剤、染料、香料、着色剤、充填剤塩、ヒドロトロープ、光活性化剤、蛍光剤、布地コンディショナー、布地柔軟剤、加水分解性界面活性剤、防腐剤、酸化防止剤、縮み防止剤、しわ防止剤、殺菌剤、殺真菌剤、カラースペックル、シルバーケア、黄ばみ防止及び/又は腐食防止剤、アルカリ源、可溶化剤、キャリア、加工助剤、顔料、及びpH調節剤、並びに香料、色相剤、界面活性剤、ビルダー、キレート剤、移染防止剤、分散剤、追加酵素、酵素安定剤、触媒材料、漂白活性化剤、過酸化水素、過酸化水素源、予形成過酸、分散剤ポリマー、泥汚れ除去/再付着防止剤、増白剤、抑泡剤、染料、香料、構造弾性化剤、布地柔軟剤、ヒドロトロープ、溶媒及びこれらの混合物を含むカプセル剤を包含するリストから1つ以上選択されてもよい(例えば、全て参照により本明細書に組み込まれる米国特許第6,610,642号、同第6,605,458号、同第5,705,464号、同第5,710,115号、同第5,698,504号、同第5,695,679号、同第5,686,014号、及び同第5,646,101号参照)。クリーニング組成物材料の具体例は以下に詳細に例示する。クリーニング及び/又は処理助剤が、クリーニング組成物中の本発明の変異型プロテアーゼと適合しない実施形態では、2つの成分を組み合わせることが適切になるまでの間、クリーニング助剤及びプロテアーゼを分離した(すなわち、互いに接触させない)ままにしておくという好ましい方法が使用される。このような分離手法には、当該技術分野において既知の任意の好適な方法が包含される(例えば、ゲルキャップ法、カプセル封入、錠剤、物理的分離など)。
しかしながら、高起泡性のリン酸ビルダー洗剤が使用されている他の地域では、例えば、限定するものではないが、他のラテンアメリカの国々では、洗浄水中に、洗剤成分が最大で約6000ppm存在している高濃度洗剤系が使用されている場合がある。
しかしながら、エネルギーの節約の観点から、多くの消費者は冷水を用いる洗浄法に切り替えている。加えて、一部の更なる地域では、一般的に洗濯並びに食器洗浄用途には冷水が使用されている。一部の実施形態では、本発明の「冷水洗浄」は、約10℃〜約40℃、又は約20℃〜約30℃、又は約15℃〜約25℃、並びに約15℃〜約35℃の範囲内の全てのその他の組み合わせ、並びに10℃〜40℃の全ての範囲の洗浄温度に好適な「冷水用洗剤」を用いる。
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。
本発明への使用が見出される市販のアミラーゼとしては、限定するものではないが、DURAMYL(登録商標)、TERMAMYL(登録商標)、FUNGAMYL(登録商標)、STAINZYME(登録商標)、STAINZYME PLUS(登録商標)、STAINZYME ULTRA(登録商標)、及びBAN(商標)(Novozymes)、並びにPOWERASE(商標)、RAPIDASE(登録商標)及びMAXAMYL(登録商標)P(Genencor)が挙げられる。
一部の実施形態では、本発明のクリーニング組成物は、組成物の約0.00001重量%〜約10重量%の濃度の追加のペルオキシダーゼ、並びに組成物の重量に基づき残部のクリーニング助剤を更に含む。本発明の一部の他の実施形態では、本発明のクリーニング組成物は、組成物の約0.0001重量%〜約10重量%、約0.001重量%〜約5重量%、約0.001重量%〜約2重量%、約0.005重量%〜約0.5重量%の濃度でペルオキシダーゼ及び/又はオキシダーゼ酵素を含む。
本発明の目的に関し、「洗浄」には擦ること及び機械的撹拌が含まれるが、これらに限定されない。一部の実施形態では、クリーニング組成物は、典型的には約500ppm〜約15,000ppmの濃度の溶液として採用される。洗浄溶媒が水である場合、水温は、典型的には、約5℃〜約90℃であり、部位が布地を含む場合、水と布地との割合は、典型的には、約1:1〜約30:1である。
小分子染料の例としては、色指数(英国染料染色学会(Society of Dyers and Colourists)(Bradford,UK))番号でダイレクトバイオレット9,ダイレクトバイオレット35、ダイレクトバイオレット48、ダイレクトバイオレット51、ダイレクトバイオレット66、ダイレクトバイオレット99、ダイレクトブルー1、ダイレクトブルー71、ダイレクトブルー80、ダイレクトブルー279、アシッドレッド17、アシッドレッド73、アシッドレッド88、アシッドレッド150、アシッドバイオレット15、アシッドバイオレット17、アシッドバイオレット24、アシッドバイオレット43、アシッドレッド52、アシッドバイオレット49、アシッドバイオレット50、アシッドブルー15、アシッドブルー17、アシッドブルー25、アシッドブルー29、アシッドブルー40、アシッドブルー45、アシッドブルー75、アシッドブルー80、アシッドブルー83、アシッドブルー90及びアシッドブルー113、アシッドブラック1、ベーシックバイオレット1、ベーシックバイオレット3、ベーシックバイオレット4、ベーシックバイオレット10、ベーシックバイオレット35、ベーシックブルー3、ベーシックブルー16、ベーシックブルー22、ベーシックブルー47、ベーシックブルー66、ベーシックブルー75、ベーシックブルー159からなる群から選択されるもの、色指数(英国染料染色学会(Society of Dyers and Colourists)(Bradford,UK))番号でアシッドバイオレット17、アシッドバイオレット43、アシッドレッド52、アシッドレッド73、アシッドレッド88、アシッドレッド150、アシッドブルー25、アシッドブルー29、アシッドブルー45、アシッドブルー113、アシッドブラック1、ダイレクトブルー1、ダイレクトブルー71からなる群から選択される小分子染料が挙げられる。ダイレクトバイオレット小分子染料が好ましい場合もある。アシッドバイオレット17、ダイレクトブルー71、ダイレクトバイオレット51、ダイレクトブルー1、アシッドレッド88、アシッドレッド150、アシッドブルー29、アシッドブルー113及びこれらの混合物から選択される染料が好ましい場合もある。
式中、R’はH、CH3、CH2O(CH2CH2O)zH、及びそれらの混合物からなる群から選択され、R”はH、CH2O(CH2CH2O)zH、及びそれらの混合物からなる群から選択され、x+y≦10であり、y≧1であり、z=0〜5である。
式中、R3はH、(CH2CH2O)zH、及びこれらの混合物からなる群から選択され、z=0〜10であり、
R4は(C1〜C16)アルキル、アリール基、及びこれらの混合物からなる群から選択される。
好ましいカプセル剤は香料を含む。好ましいカプセル剤は、メラミンホルムアルデヒド及び/又は架橋メラミンホルムアルデヒドを含んでもよいシェルを含む。コア材料とシェルとを含み、上記シェルが上記コア材料を少なくとも部分的に取り囲む、好適なカプセル剤が開示される。上記カプセル剤の少なくとも75%、85%又は更には90%は、0.2MPa〜10MPaの破壊強度、及び最初の全封入有益剤を基準にして0%〜20%、又は更には10%若しくは5%未満の有益剤漏出率を有してもよい。好ましくは、上記カプセル剤の少なくとも75%、85%又は更には90%が(i)1ミクロン〜80ミクロン、5ミクロン〜60ミクロン、10ミクロン〜50ミクロン、又は更には15ミクロン〜40ミクロンの粒径を有してもよく、及び/又は(ii)上記カプセル剤の少なくとも75%、85%又は更には90%が30nm〜250nm、80nm〜180nm、又は更には100nm〜160nmの粒子壁厚を有してもよい。ホルムアルデヒドスカベンジャーをカプセル剤と共に(例えばカプセルスラリーに)使用してもよく、及び/又は、その添加はこのような組成物にカプセル剤を加える前、最中、又は後に行われてもよい。好適なカプセル剤は、米国特許第2008/0305982(A1)号、及び/又は同第2009/0247449(A1)号の教示に従うことにより、製造することができる。あるいは、好適なカプセル剤は、Appleton Papers Inc.(Appleton,Wisconsin USA)から購入することもできる。
(IV) −[(OCHR1−CHR2)a−O−OC−Ar−CO−]d
(V) −[(OCHR3−CHR4)b−O−OC−sAr−CO−]e
(VI) −[(OCHR5−CHR6)c−OR7]f
式中、
a、b、及びcは、1〜200であり、
d、e、及びfは、1〜50であり、
Arは、1,4−置換フェニレンであり、
sArは、位置5をSO3Meにより置換された、1,3−置換フェニレンであり、 Meは、Li、K、Mg/2、Ca/2、Al/3、アンモニウム、モノ−、ジ−、トリ−、若しくはテトラアルキルアンモニウム(アルキル基は、C1〜C18アルキル又はC2〜C10ヒドロキシアルキルである)、又はこれらの混合物であり、 R1、R2、R3、R4、R5、及びR6は、独立して、H、又はC1〜C18 n−若しくはイソ−アルキルから選択され;
R7は、直鎖若しくは分枝鎖C1〜C18アルキル、又は直鎖若しくは分枝鎖C2〜C30アルケニル、又は炭素原子を5〜9個有するシクロアルキル基、又はC8〜C30アリール基、又はC6〜C30アリールアルキル基である。
(a)サブチリシン(EC 3.4.21.62)(Bacillus lentus、B.alkalophilus、B.subtilis、B.amyloliquefaciens、Bacillus pumilus及びBacillus gibsoniiなどのBacillusから誘導されたものを含む)(米国特許第6,312,936(B1)号、同第5,679,630号、同第4,760,025号、同第7,262,042号及び国際公開第09/021867号に記載)。
Enzymesより、Opticlean(登録商標)及びOptimase(登録商標)の商標名で販売されているもの、Henkel/Kemiraより入手可能なもの、すなわちBLAP(以下の変異S99D+S101R+S103A+V104I+G159Sを有する、米国特許第5,352,604号の図29で示される配列、以降BLAPと呼ぶ)、BLAP R(S3T+V4I+V199M+V205I+L217Dを有するBLAP)、BLAP X(S3T+V4I+V205Iを有するBLAP)及びBLAP F49(S3T+V4I+A194P+V199M+V205I+L217Dを有するBLAP)(以上、全てHenkel/Kemira)、並びに花王のKAP(変異A230V+S256G+S259Nを有するバチルス・アルカロフィルスのサブチリシン)が挙げられる。
9375(米国特許第7,153,818号)、DSM 12368、DSMZ no.12649、KSM AP1378(国際公開第97/00324号)、KSM K36又はKSM K38(欧州特許第1,022,334号)に由来する。好ましいアミラーゼには次のものが挙げられる。
26、30、33、82、37、106、118、128、133、149、150、160、178、182、186、193、203、214、231、256、257、258、269、270、272、283、295、296、298、299、303、304、305、311、314、315、318、319、339、345、361、378、383、419、421、437、441、444、445、446、447、450、461、471、482、484のうちの1つ以上が置換された変異体であって、好ましくはD183*及びG184*の欠損を含有する変異体。
好ましくは、ペルオキシ酸又はその塩は、ペルオキシヘキサン酸、ペルオキシヘプタン酸、ペルオキシオクタン酸、ペルオキシノナン酸、ペルオキシデカン酸、任意のその塩、又は任意のこれらの組み合わせから選択される。特に好ましいペルオキシ酸は、フタルイミドペルオキシアルカン酸、特にε−フタルイミドペルオキシヘキサン酸(PAP)である。好ましくは、ペルオキシ酸又はその塩は、30℃〜60℃の範囲の融点を有する。
(4)R−(C=O)−Lを有する漂白活性化剤(式中、Rはアルキル基であり、所望により分枝状であり、漂白活性化剤が疎水性の場合には、6〜14個の炭素原子、又は8〜12個の炭素原子を有し、漂白活性化剤が親水性の場合、6個未満の炭素原子、又は更に4個未満の炭素原子を有し、Lは脱離基である)。好適な脱離基の例は、安息香酸及びそれらの誘導体−特にベンゼンスルホネートである。好適な漂白活性化剤としては、ドデカノイルオキシベンゼンスルホネート、デカノイルオキシベンゼンスルホネート、デカノイルオキシ安息香酸又はその塩、3,5,5−トリメチルヘキサノイルオキシベンゼンスルホネート、テトラアセチルエチレンジアミン(TAED)及びノナノイルオキシベンゼンスルホネート(NOBS)が挙げられる。好適な漂白活性化剤はまた、国際公開第98/17767号に開示されている。任意の好適な漂白活性化剤を使用してもよいが、発明の一態様では、対象組成物は、NOBS、TAED又はこれらの混合物を含んでよい。
式中、Rは直鎖又は分枝鎖、置換又は非置換の、C6〜18アルキル又はアルケニル部分であり、R1及びR2は、独立して、メチル又はエチル部分から選択され、R3は、ヒドロキシル、ヒドロキシメチル、又はヒドロキシエチル部分であり、Xは、電気的中性を提供するアニオンであり、好適なアニオンとしては、例えば、塩化物といったハロゲン化物、サルフェート、及びスルホネートが挙げられる。好適なカチオン性洗浄界面活性剤は、モノC6〜18アルキルモノヒドロキシエチルジメチル第四級アンモニウムクロリドである。非常に好適なカチオン性洗浄界面活性剤は、モノ−C8〜10アルキルモノヒドロキシエチルジメチル四級アンモニウムクロリド、モノ−C10〜12アルキルモノヒドロキシエチルジメチル四級アンモニウムクロリド、及びモノ−C10アルキルモノヒドロキシエチルジメチル四級アンモニウムクロリドである。
本明細書で用いるのに好適な他のキレート剤は、市販されているDEQUESTシリーズ、並びにMonsanto、DuPont、及びNalco,Inc.のキレート剤である。
このような好適なカチオン性ポリマーの平均分子量は一般に、約10,000〜10,000,000であり、一実施形態では、約50,000〜約5,000,000であり、別の実施形態では、約100,000〜約3,000,000である。
好ましくは、0.5%〜3%の脂肪モノカルボン酸塩抑泡剤が利用される。シリコーン抑泡剤は、典型的には、最大で洗剤組成物の2.0重量%の量で利用されるが、より多くの量で使用されてもよい。モノステアリルリン酸塩泡抑制剤は、概して、組成物の0.1重量%〜2重量%の範囲の量で利用される。炭化水素抑泡剤は、典型的には、0.01%〜5.0%の範囲の量で利用されるが、より高い濃度を使用することができる。アルコール石鹸泡抑制剤は、典型的には、完成した組成物の0.2%〜3重量%で使用される。
Chemicals Buyers Directory 80th Annual Editionに提供されている。例えば4、5、6、7種又はそれ以上の、複数の香料組成物が本発明の組成物中に存在するのが通常である。香料混合物において、好ましくは15〜25重量%はトップノートである。トップノートはPoucher(Journal of the Society of Cosmetic Chemists 6(2):80[1995])に定義されている。好ましいトップノートとしては、ローズオキシド、柑橘油、酢酸リナリル、ラベンダー、リナロール、ジヒドロミルセノール及びシス−3−ヘキサノールが挙げられる。
本発明は、上記の変異体の少なくとも1つを得る工程と、それを助剤又はその混合物と混合する工程とを含む、上記の組成物の製造方法も提供する。
本発明は、表面、特に布地を処理する方法も提供し、この方法は上記の変異体の少なくとも1つと助剤とを含む水性リカーと表面とを接触させる工程を含む。典型的には、プロテアーゼ変異体及び助剤は、本発明の組成物を水に添加することによって洗浄液を形成するために水に添加される。本発明の方法で処理される表面は、食器、洗濯物、硬質表面、コンタクトレンズ等のようないかなる布地ケア又はホームケアの洗浄対象表面であってもよい。一部の実施形態では、表面の少なくとも一部を、未希釈形態又は好ましくは洗浄液に希釈された本発明のクリーニング組成物の少なくとも1つの実施形態と接触させ、この表面が洗浄され、任意にすすがれる。本発明の目的上、「洗浄すること」は、浸漬すること、擦ること、及び機械的洗浄を包含するがこれらに限定されない。一部の実施形態では、本発明のクリーニング組成物は、溶液中約500ppm〜約15,000ppmの濃度で使用される。洗浄溶媒が水である一部の実施形態では、水温は、典型的には約5℃〜約90℃の範囲である。
本発明は、以降の実施例により、更に詳細に記載されるが、この記載により本発明の範囲が請求されたものとして、本発明の範囲を制限することを意図するものではない。
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(タカラバイオ株式会社、大津、日本)、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)。
2 −NHにつき20個のエトキシル基を有するポリエチレンイミン(MW=600)。
3 両親媒性グリース洗浄ポリマーは、−NHにつき24個のエトキシル基、及び−NHにつき16個のプロポキシル基を有するポリエチレンイミン(MW=600)である。
4 次の構造を有する可逆性プロテアーゼ抑制剤。
界面活性剤材料は、次の企業から得ることができる:BASF(Ludwigshafen,Germany)(Lutensol(登録商標));Shell Chemicals(London,UK);Stepan(Northfield,Illinois,USA);Huntsman(Huntsman,Salt Lake City,Utah,USA);Clariant(Sulzbach,Germany(Praepagen(登録商標)))。
2として入手することができる。
アッセイ及び試験方法
本実施例は、本発明の展開に使用される様々な試験方法及びアッセイを記載する。提供されるプロトコール由来の任意の変法が関連する実施例に示される。
試験方法1
染料又は顔料材料が本発明の意図する布地色相剤であるか否かを定義するためのプロトコールを以下に記載する。
試験方法2では、顆粒型洗剤組成物10(上記表Dを参照されたい)を用い、以下に記載のBMIマイクロスウォッチアッセイを実施する。洗濯洗剤を、12gpgの硬度を有する水に溶解させ、16℃の温度に調整し、所望のプロテアーゼ変異体酵素を添加する。
次いで、記載されるBMIマイクロスウォッチアッセイに従って酵素変異体の性能を測定する。性能指数は、プロテアーゼ変異体酵素の性能を、配列番号2のアミノ酸配列を有するB.レンタスのGG36サブチリシン酵素と比較することで決定する。全ての条件で、酵素の使用濃度は0.1〜5ppm範囲である。プロテアーゼ変異体酵素のうち、性能指数1.1以上のものが冷水用プロテアーゼとして示される。
試験方法3では、顆粒型洗剤組成物7(上記表Dを参照されたい)を用い、以下に記載のBMIマイクロスウォッチアッセイを実施する。洗濯洗剤を、6gpgの硬度を有する水に溶解させ、16℃の温度に調整し、所望のGG36プロテアーゼ変異体酵素を添加する。次いで、記載されるBMIマイクロスウォッチアッセイに従ってプロテアーゼGG36の酵素変異体の性能を測定する。性能指数は、プロテアーゼGG36の変異型酵素の性能を、配列番号2のアミノ酸配列を有するB.レンタスのGG36サブチリシン酵素と比較することで決定する。全ての条件で、酵素の使用濃度は0.1〜5ppm範囲である。
プロテアーゼGG36の変異体のうち、性能指数1.1以上のものが冷水用プロテアーゼとして示される。
試験方法4では、顆粒型洗剤組成物7(上記表Dを参照されたい)を用い、BMIマイクロスウォッチアッセイを実施する。洗濯洗剤を、6gpgの硬度を有する水に溶解させ、16℃の温度に調整し、所望のGG36プロテアーゼ変異体酵素を添加する。次いで、記載されるBMIマイクロスウォッチアッセイに従ってプロテアーゼGG36の酵素変異体の性能を測定する。性能指数は、GG36プロテアーゼ変異体酵素の性能を参照酵素GG36−A158Eの性能と比較することによって決定され、GG36−A158E参照酵素は配列番号2のB.レンタスのサブチリシンGG36プロテアーゼのアミノ酸配列の位置158でアラニンがグルタミン酸へと単独置換(すなわち、A158E変異)されており、全ての場合で酵素投与量は0.1〜5ppmの範囲である。性能指数1.0以上のプロテアーゼGG36変異体が、冷水用プロテアーゼとして示される。
試験方法6では、表1−2の洗剤36a〜36nのうちのいずれか1種を用いてBMIマイクロスウォッチアッセイを実施する。表1〜2に記載の水硬度を有する水に洗剤を溶解させ、水温を16℃に調整する。次いで、記載されるBMIマイクロスウォッチアッセイに従って酵素変異体の性能を測定する。性能指数は、変異体の性能を配列番号2の酵素の性能と比較することで決定され、全ての場合で酵素投与量は0.1〜5ppmの範囲である。酵素のうち、性能指数1.1以上のものが冷水用プロテアーゼとして示される。
試験方法7では、表1の洗剤のいずれか1種を用いてBMIマイクロスウォッチアッセイを実施する。表1に記載の水硬度及び緩衝剤を有する水に洗剤を溶解し、水温を16℃又は25℃に調整する。次いで、記載されるBMIマイクロスウォッチアッセイに従って酵素変異体の性能を測定する。性能指数は、変異体の性能を配列番号2の酵素の性能と比較することで決定され、全ての場合で酵素投与量は0.1〜5ppmの範囲である。酵素のうち、性能指数1.1以上のものが冷水用プロテアーゼとして示される。
タンパク質含量を測定するためのTCAアッセイ
加湿条件下でエアレーションしながら250〜300rpmで振盪し、B.サブチリスを37℃で2〜3日増殖させた。酵素を含有している培養上清から遠心沈降及び/又は濾過により細胞を除去した。TCA沈降アッセイを用い、プロテアーゼ/タンパク質/酵素濃度を測定した。100μL/ウェルの0.25NのHClを含有させた96ウェルの平底マイクロタイタープレート(MTP;Costar 9017中結合型透明ポリスチレンプレート)に培養上清のアリコート(20〜25uL)を移した。読み取り「基底値」は、試料を混合した5秒後に405nmで光散乱/吸光を読み取ることで測定した。HClを含有しているプレートに100μL/ウェルの30%(重量/体積)のトリクロロ酢酸(TCA)を加え、室温で10分間インキュベートし、タンパク質の沈殿を促進させた。試料を混合した5秒後に、405nmでこの「試験」プレートの光散乱/吸光度を測定した。試料における濁度/光散乱の増加は、培養上清中の沈殿可能なタンパク質の合計量に相関する。「基底」読み取り値(HClの添加後に得られる)を「試験」読み取り値(TCAの添加後に得られる)から減算することで算出し、存在する総タンパク質を相対的に測定した。タンパク質沈殿とタンパク質濃度を関連づける換算率を、既知濃度のGG36標準について求めた。沈殿は濃度と線形関係にあることから、この換算率は全ての変異体に使用できる。必要に応じて、TCA読み取り値を比活性が既知であるクローンのAAPFプロテアーゼアッセイ(以下に記載)により較正することで、検量線を作成することができる。しかしながら、TCA結果は、50〜500百万分率のタンパク質濃度(ppm)(ここで、1ppmは1mg/Lに相当する)に対して線形であることから、所望の性能を有する変異体を選択するために、酵素性能に対して直接プロットすることができる。
セリンプロテアーゼ変異体、より具体的にはサブチリシン変異体のプロテアーゼ活性を測定するために、N−スクシニル−L−アラニル−L−アラニル−L−プロリル−L−フェニル−p−ニトロアニリド(suc−AAPF−pNA)の加水分解を計測した。使用した試薬溶液は、以下のものであった:0.005%のTWEEN(登録商標)−80を含有している100mMのトリス/HCl(pH 8.6)(トリス希釈緩衝液)、1mMのCaCl2及び0.005%のTWEEN(登録商標)−80を含有している100mMトリス緩衝液(pH 8.6)(トリス/Ca緩衝液)、並びに160mMのsuc−AAPF−pNA/DMSO(suc−AAPF−pNA保存溶液)(Sigma:S−7388)。suc−AAPF−pNA希釈標準溶液を調製するために、1mLのsuc−AAPF−pNA原液を100mLのトリス/Ca緩衝液に加え、少なくとも10秒にわたってウェルをよく混合した。10μLの希釈プロテアーゼ溶液を96ウェルMTPの各ウェルに加え、直ちに1mg/mLのsuc−AAPF−pNA希釈標準溶液190μLを加えてアッセイを実施した。溶液を5秒にわたって混合し、吸光度の変化を、25℃にて、405nmで、MTPリーダーの動的解析モードにより読み取りした(5分毎に25回読み取り)。プロテアーゼ活性はAUとして表記される(活性=ΔOD・min−1 ml−1)。
96ウェルのマイクロタイタープレート(MTP;Corning 3641)中に入れる、予洗し、パンチで型通りに切り取り、血液、ミルク及びインク(BMI)により染色した直径5.5ミリメートルのマイクロスウォッチ(EMPA116)を、Center for Testmaterials BV(Vlaardingen,The Netherlands)から得た。
x=(対象ppm)(vb)/(y−対象ppm)
式中、x=酵素量,y=酵素濃度,vb=緩衝液量
Versispan 8チャンネルアームを持つPerkin−Elmer Janusロボットを使用し、コンダクティブチップを用い原液プレート(TCA酵素濃度アッセイで使用し回収した変異体をプールした、Axygenの深さ半分のウェルプレート)から緩衝液を入れた試験プレートへと様々な容量の酵素を分注した。試料を上下に3回ピペッティングして混合した。均等化したプレートのAAPF活性を測定し、母液プレートと比較することで、酵素希釈の正確さを評価し、性格な希釈がなされたか検証した。
性能指数は、同じタンパク質濃度下で変異体性能(実測値)と標準酵素性能(理論値)とを比較する。加えて、理論値は、標準プロテアーゼの性能用量反応曲線のパラメーターを用いて算出することができる。
GG36の変異体及びコンビナトリアルライブラリの構築
本例は、B.サブチリス発現プラスミドpHPLT−GG36を用いてB.サブチリスに構築されたGG36変異体及びライブラリの冷水クリーニングについて記載する。このB.サブチリスの発現プラスミドは、以下に示すGG36発現カセット、B.リケニフォルミスのLATプロモーター(Plat)、並びにレプリカーゼ遺伝子(reppUB)、ネオマイシン/カナマイシン耐性遺伝子(neo)及びブレオマイシン耐性マーカー(bleo)等のpUB110由来の更なる要素(McKenzie et al.,Plasmid,15:93〜103,1986)(米国特許第6,566,112号、図4を参照)を含有する。pHPLT−GG36プラスミドマップは国際公開第2011140364号に提供されている。GG36発現カセット配列は以下に提供されるものである。
Templiphiキット(GE Healthcare)によるローリング・サークル増幅を用いて製造業者の指示に従って増幅し、バチルス・サブチリスの形質転換のための多重結合DNAを作製した。ローリング・サークル増幅産物を100倍希釈し、B.サブチル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(QIAprep Spinミニプレップキット、Qiagen)。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。実施例1(TCAアッセイ)に記載のようにB.サブチルス細胞(遺伝子型:ΔaprE、ΔnprE、amyE::xylRPxylAcomK−phleo)で変異体を発現させ、実施例1に記載のようにBMIマイクロスウォッチクリーニングアッセイを用いて更に特性決定した。下の表中で、洗剤組成物(「洗剤」)は、上記表1に示されるものと対応する。同様に、記載のように、アミノ酸位置はBPN’の番号付けに従って列挙される。
Claims (11)
- 助剤と、単離されたサブチリシン変異体と、を含むクリーニング及び/又は処理組成物であって、前記サブチリシン変異体が、バチルス・レンタスのサブチリシンGG36プロテアーゼに対して少なくとも90%のアミノ酸同一性を有するバチルス・レンタスのサブチリシンGG36プロテアーゼの変異体であり、かつ次から選択される位置にアミノ酸置換の組み合わせを含むアミノ酸配列を含み:T022A−S103A−V104I−N116L−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101G−V104I−N116L−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−N116L−G159D−S188D−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−N116L−S188D−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−N116L−G159D−A232V−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−N116L−G159D−S188D−Q245R−N248D−E271F,T022A−S101G−S103A−V104I−N116L−G159D−S188D−A232V−N248D−E271F,T022A−S101G−S103A−V104I−N116L−G159D−S188D−A232V−Q245R−E271F,またはT022A−S101G−S103A−V104I−N116L−G159D−S188D−A232V−Q245R−N248D−E271F、サブチリシン変異体のアミノ酸位置が配列番号1に示すバチルス・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、前記サブチリシン変異体の置換が、配列番号2に示すバチルス・レンタスのサブチリシンGG36プロテアーゼに従って存在する、クリーニング及び/又は処理組成物。
- 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に示すアミノ酸配列を含む、請求項1に記載の組成物。
- 前記単離されたサブチリシン変異体の総正味電荷が、前記バチルス・レンタスのサブチリシンGG36プロテアーゼの総正味電荷を基準にして−1、0、+1、+2、+3、+4、+5、−1、−2、−3、−4、又は−5である、請求項1または2に記載の組成物。
- 前記変異体の総正味電荷が、前記バチルス・レンタスのサブチリシンGG36プロテアーゼの総正味電荷を基準にして+1、0、−1、−2、−3、又は−4である、請求項3に記載の単離されたサブチリシン変異体。
- 前記単離されたサブチリシン変異体の総正味電荷が、次から選択される1つ以上の置換によって得られ:A001E、V004E、R010H/A、Q012E、A015D、N018D、R019H/S、V026D、K027E、N043D、R045C/T/S/P、S049D、V051E、G061E、N062D/E、N076D、N077D、S078D、S087D、A098E、S101D、S106E、G115E、G118D、N123D、S128D、P129E、S130D/E、S132D、A158E、G159D/E、S160D、S166D、R170T、N183D、N184D、N185E、R186H、S188D/E、A194E、A200D、Y209E、A215D、N204D、S212D、L217D/E、N218D、A230E、K235F、N237D、K237E、N238D、S240D、N243D、Q245D、R247L、N248D/E、K251C、N263D、N269D/E、A272D、A273E、又はR275H/S、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、請求項1〜4のいずれか一項に記載のクリーニング及び/又は処理組成物。
- 前記単離されたサブチリシン変異体の総正味電荷が、次から選択される1つ以上の置換によって得られ:A001R、V004R、Q012R、P014R、H017R、N018R/K、G020K/R、T022R/K、S024R/K、G025R、D032I、D041K/L/N、N043R/K、G046R、A048R、F050R/K、P055R、S056R/K、T057R、Q059K、G061R、N076K、S078R、P086R、S087R、E089G/P/I、G097R、S099R、Q109R、G115R、G118R、S132K、S144R、G159R/K、D181C/S/T、L196K、N204K、Q206R、K235R、Q236R/K、K237R、N238R、S240R、W241R、S242R/K、V244R、Q245R/K、N248R、H249R、N252R/K、S256R、G258R、T260K、N269R/K、又はE271F/H/T/L/W/R/S/I/A/G/V、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、請求項1〜5のいずれか一項に記載のクリーニング及び/又は処理組成物。
- 前記単離されたサブチリシン変異体が、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;b)試験方法3による性能指数が少なくとも1.1;c)試験方法4による性能指数が少なくとも1.0;及び/又はd)試験方法6による性能指数が少なくとも1.0;及び/又はe)試験方法7による性能指数が少なくとも1.1である、の1つ以上を有する、請求項1〜6のいずれか一項に記載のクリーニング及び/又は処理組成物。
- 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、少なくとも1つの追加を更に含む、請求項1〜7のいずれか一項に記載の組成物。
- 前記助剤を前記プロテアーゼ変異体と混合する工程を含む、請求項1〜8のいずれか一項に記載の組成物の製造方法。
- 請求項1〜8のいずれか一項に記載の組成物を含む水性洗浄液と、表面とを接触させる工程を含む、表面の処理方法。
- 前記水性洗浄液が0.1〜3mS/cmの伝導度を有する、請求項10に記載の方法。
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