JP6643987B2 - ケトン化合物およびアミン化合物の還元的アミノ化のための操作されたイミンレダクターゼおよび方法 - Google Patents
ケトン化合物およびアミン化合物の還元的アミノ化のための操作されたイミンレダクターゼおよび方法 Download PDFInfo
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 101150016309 trpC gene Proteins 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000005199 ultracentrifugation Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 101150110790 xylB gene Proteins 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
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- C12Y105/01028—Opine dehydrogenase (1.5.1.28)
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Description
技術分野
配列表、表、またはコンピュータプログラムに関する言及
キラルな第二級アミンおよび第三級アミンは、医薬品産業において重要な構成物質である。このキラルアミン化合物クラスを生成するための効率的な生体触媒経路は知られていない。既存の化学的方法は、キラルホウ素試薬または多工程合成を使用する。
産業的に適用可能な条件下でのキラルな第二級アミンおよび第三級アミンの合成のための生体触媒およびその使用プロセスが当該分野で必要とされている。
本発明は、基質として非活性化ケトンおよび非活性化アミンを使用した直接還元的アミノ化によるキラルな第二級アミンおよび第三級アミンの合成のための新規の生体触媒およびこの生体触媒の関連する使用方法を提供する。本発明の生体触媒は、配列番号2のアミノ酸配列を有するオピンデヒドロゲナーゼをコードするArthrobacter sp.1C株由来の初期野生型遺伝子の指向進化によって生成された、配列番号6の操作された酵素の指向進化によって誘導された操作されたポリペプチドバリアントである。これらの操作されたポリペプチドは、第二級アミン生成物化合物(product compound)または第三級アミン生成物化合物を形成するためのケトン基質(シクロヘキサノンおよび2−ペンタノンなどの非活性化ケトン基質が含まれる)またはアルデヒド基質および第一級アミン基質または第二級アミン基質(ブチルアミン、アニリン、メチルアミン、およびジメチルアミンなどの非活性化アミン基質が含まれる)の変換を触媒することができる。オピンデヒドロゲナーゼから誘導されたこれらの操作されたポリペプチドの酵素活性を「イミンレダクターゼ活性」といい、本明細書中に開示の操作された酵素を「イミンレダクターゼ」または「IRED」ともいう。一般的なIREDのイミンレダクターゼ活性を、以下のスキーム1に示す。
(i)配列番号6の参照配列と比較した場合に、X12、X18、X26、X27、X57、X65、X87、X93、X96、X126、X138、X140、X142、X159、X170、X175、X177、X195、X200、X221、X234、X241、X242、X253、X254、X257、X262、X263、X267、X272、X276、X277、X278、X281、X282、X291、およびX352から選択される位置での1つの残基の相違であって、任意選択的に、前記位置での残基の相違が、X12M、X18G、X26M/V、X27S、X57D/L/V、X65I/V、X87A、X93G/Y、X96C、X126S、X138L、X140M、X142A、X159C/L/Q/V、X170F/K/R/S、X175R、X177R、X195S、X200S、X221F、234C/L、X241K、X242C/L、X253K/N、X254R、X257Q、X262F/G/P/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X267E/G/H/I/N/S、X272D、X276L、X277H/L、X278E/H/K/N/R/S/W、X281A、X282A/R、X291E、およびX352Qから選択される、1つの残基の相違;
(ii)配列番号6の参照配列と比較した場合に、X20V、X29K、X37P、X74W、X82C/T、X94N、X108S、X111A/H、X141M/N、X143F/L/Y、X153F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X163V、X197V、X201I、X220C/K/Q、X223S、X256A/E/I/L/S/T、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X264V、X270L、X273C、X274L/S、X279T、X284C/F/H/P/Q/S、X292E/P、およびX295Fから選択される1つの残基の相違;および/または
(iii)配列番号6の参照配列と比較した場合に、X82P、X141W、X153Y、X154F、X259I/L/M、X274L/M、X283V、およびX296N/Vから選択される2つまたはそれを超える残基の相違;
のうちの少なくとも1つを有するアミノ酸配列を含み、
前記ポリペプチドはイミンレダクターゼ活性を有する、操作されたポリペプチドを提供する。
(a)X153Y、およびX283V;
(b)X141W、X153Y、およびX283V;
(c)X141W、X153Y、X274L/M、およびX283V;
(d)X141W、X153Y、X154F、X274L/M、およびX283V;
(e)X141W、X153Y、X154F、およびX283V;
(f)X141W、X153Y、X283V、およびX296N/V;
(g)X141W、X153Y、X274L/M、X283V、およびX296N/V:
(h)X111A、X153Y、X256E、X274M、およびX283V;
(i)X111A、X141W、X153Y、X273C、X274M、X283V、およびX284S;
(j)X111A、X141W、X153Y、X273C、およびX283V;
(k)X111A、X141W、X153Y、X154F、X256E、X274M、X283V、X284S、およびX296N;
(l)X111A、X141W、X153Y、X256E、X273W、X274L、X283V、X284S、およびX296N;
(m)X111H、X141W、X153Y、X273W、X274M、X284S、およびX296N;
(n)X111H、X141W、X153Y、X154F、X273W、X274L、X283V、X284S、およびX296N;
(o)X82P、X141W、X153Y、X256E、X274M、およびX283V;
(p)X82P、X111A、X141W、X153Y、X256E、X274M、X283V、M284S、およびE296V;
(q)X94N、X143W、X159L、X163V、X259M、およびX279L;
(r)X141W、X153Y、X154F、およびX256E;および
(s)X153Y、X256E、およびX274M
から選択される残基の相違の少なくとも1つの組み合わせを含むアミノ酸配列を含む。
(a)X156N;
(b)X37P、X82T、およびX156N;
(c)X37P、X82T、X156N、およびX259I;
(d)X259L/M;
(e)X82T、X156N、X223S、X259L、X267G、およびX281A;
(f)X263C;
(g)X12M、X261H、X263C、X277L、およびX292E;
(h)X154S;および
(i)X154S、X156M、X260D、X261H、X262P、X263E、およびX284Pから選択される少なくとも1つの残基の相違または残基の相違の組み合わせを含むアミノ酸配列を含む。
R1およびR2は上記定義の通りである)の化合物;および式(II)
本発明の特定の態様では、例えば以下の項目が提供される:
(項目1)
操作されたポリペプチドであって、配列番号6の参照配列と少なくとも80%の配列同一性および以下の特徴:
(i)配列番号6の前記参照配列と比較した場合に、X12、X18、X26、X27、X57、X65、X87、X93、X96、X126、X138、X140、X142、X159、X170、X175、X177、X195、X200、X221、X234、X241、X242、X253、X254、X257、X262、X263、X267、X272、X276、X277、X278、X281、X282、X291、およびX352から選択される位置における残基の相違であって、任意選択的に、前記位置における前記残基の相違が、X12M、X18G、X26M/V、X27S、X57D/L/V、X65I/V、X87A、X93G/Y、X96C、X126S、X138L、X140M、X142A、X159C/L/Q/V、X170F/K/R/S、X175R、X177R、X195S、X200S、X221F、234C/L、X241K、X242C/L、X253K/N、X254R、X257Q、X262F/G/P/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X267E/G/H/I/N/S、X272D、X276L、X277H/L、X278E/H/K/N/R/S/W、X281A、X282A/R、X291E、およびX352Qから選択される、1つの残基の相違;
(ii)配列番号6の前記参照配列と比較した場合に、X20V、X29K、X37P、X74W、X82C/T、X94N、X108S、X111A/H、X141M/N、X143F/L/Y、X153E/F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X163V、X197V、X201I、X220C/K/Q、X223S、X256A/E/I/L/S/T、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X264V、X270L、X273C、X274L/S、X279T、X284C/F/H/P/Q/S、X292E/P、およびX295Fから選択される残基の相違;および/または
(iii)配列番号6の前記参照配列と比較した場合に、X153Y、X283V、X82P、X141W、X154F、X259I/L/M、X274L/M、およびX296N/Vから選択される2つまたはそれを超える残基の相違;
のうちの少なくとも1つを有するアミノ酸配列を含み、
前記ポリペプチドがイミンレダクターゼ活性を有する、操作されたポリペプチド。
(項目2)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X12M、X37P、X82T、X111A、X154S、X156N/M、X223S、X256E、X260D、X261H、X262P、X263C/E/Q、X267G、X277L、X281A、X284P/S、およびX292Eから選択される少なくとも1つの残基の相違を含む、項目1に記載の操作されたポリペプチド。
(項目3)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X256E、X93G/Y、X94N、X96C、X111A/H、X142A、X159L、X163V、X259R、X273C、およびX284P/Sから選択される少なくとも1つの残基の相違を含む、項目1に記載の操作されたポリペプチド。
(項目4)
前記アミノ酸配列は、配列番号6の前記参照配列と比較した場合に、X82C/P/T、X141W、X143W、X153Y、X154F/Q/Y、X256V、X259I/L/M/T、X260G、X261R、X265L、X273W、X274M、X277A/I、X279L、X283V、X284L、X296N、X326Vから選択される少なくとも2つの残基の相違を含む、項目1に記載の操作されたポリペプチド。
(項目5)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、以下:
(a)X153Y、およびX283V;
(b)X141W、X153Y、およびX283V;
(c)X141W、X153Y、X274L/M、およびX283V;
(d)X141W、X153Y、X154F、X274L/M、およびX283V;
(e)X141W、X153Y、X154F、およびX283V;
(f)X141W、X153Y、X283V、およびX296N/V;
(g)X141W、X153Y、X274L/M、X283V、およびX296N/V;
(h)X111A、X153Y、X256E、X274M、およびX283V;
(i)X111A、X141W、X153Y、X273C、X274M、X283V、およびX284S;
(j)X111A、X141W、X153Y、X273C、およびX283V;
(k)X111A、X141W、X153Y、X154F、X256E、X274M、X283V、X284S、およびX296N;
(l)X111A、X141W、X153Y、X256E、X273W、X274L、X283V、X284S、およびX296N;
(m)X111H、X141W、X153Y、X273W、X274M、X284S、およびX296N;
(n)X111H、X141W、X153Y、X154F、X273W、X274L、X283V、X284S、およびX296N;
(o)X82P、X141W、X153Y、X256E、X274M、およびX283V;
(p)X82P、X111A、X141W、X153Y、X256E、X274M、X283V、M284S、およびE296V;
(q)X94N、X143W、X159L、X163V、X259M、およびX279L;
(r)X141W、X153Y、X154F、およびX256E;および
(s)X153Y、X256E、およびX274M
から選択される残基の相違の少なくとも1つの組み合わせを含む、項目1に記載の操作されたポリペプチド。
(項目6)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X12M、X18G、X20V、X26M/V、X27S、X29K、X37P、X57D/L/V、X65I/V、X74W、X82C/T、X87A、X93G/Y、X94N、X96C、X108S、X111A/H、X126S、X138L、X140M、X141M/N、X142A、X143F/L/Y、X153E/F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X159C/L/Q/V、X163V、X170F/K/R/S、X175R、X177R、X195S、X197V、X200S、X201I、X220C/K/Q、X221F、X223S、X234V/C/L、X241K、X242C/L、X253K/N、X254R、X256A/E/I/L/S/T、X257Q、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X262P、X262F/G/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X264V、X267E/G/H/I/N/S、X270L、X272D、X273C、X274L/S、X276L、X277H/L、X278E/H/K/N/R/S/W、X279T、X281A、X282A/R、X284C/F/H/P/Q/S、X291E、X292E/P、X295F、およびX352Qから選択される少なくとも1つの残基の相違をさらに含む、項目5に記載の操作されたポリペプチド。
(項目7)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X12M、X37P、X82T、X111A、X141W、X153Y、X154F/S、X156N/M、X223S、X256E、X259I、X260D、X261H、X262P、X263C/E/Q、X267G、X274M、X277L、X281A、X283V、X284P/S、X292E、およびX296Nから選択される少なくとも1つの残基の相違をさらに含む、項目5に記載の操作されたポリペプチド。
(項目8)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、残基の相違X111A、X141W、X153Y、X154F、X256E、X274M、X283V、X284S、およびX296N、ならびに以下:
(a)X156N;
(b)X37P、X82T、およびX156N;
(c)X37P、X82T、X156N、およびX259I;
(d)X259L/M;
(e)X82T、X156N、X223S、X259L、X267G、およびX281A;
(f)X263C;
(g)X12M、X261H、X263C、X277L、およびX292E;
(h)X154S;および
(i)X154S、X156M、X260D、X261H、X262P、X263E、およびX284P
から選択される少なくとも1つの残基の相違または残基の相違の組み合わせを含む、項目1に記載の操作されたポリペプチド。
(項目9)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X29、X137、X157、X184、X197、X198、X201、X220、X232、X261、X266、X279、X280、X287、X288、X293、X295、X311、X324、X328、X332、およびX353から選択される残基の位置に残基の相違を含まない、項目1に記載の操作されたポリペプチド。
(項目10)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X4H/L/R、X5T、X14P、X20T、X29R/T、X37H、X67A/D、X71C/V、X74R、X82P、X94K/R/T、X97P、X100W、X111M/Q/R/S、X124L/N、X136G、X137N、X141W、X143W、X149L、X153E/V/Y、X154F/M/Q/Y、X156G/I/Q/S/T/V、X157D/H/L/M/N/R、X158K、X160N、X163T、X177C/H、X178E、X183C、X184K/Q/R、X185V、X186K/R、X197I/P、X198A/E/H/P/S、X201L、X220D/H、X223T、X226L、X232G/A/R、X243G、X246W、X256V、X258D、X259E/H/I/L/M/S/T/V/W、X260G、X261A/G/I/K/R/S/T、X265G/L/Y、X266T、X270G、X273W、X274M、X277A/I、X279F/L/V/Y、X280L、X283M/V、X284K/L/M/Y、X287S/T、X288G/S、X292C/G/I/P/S/T/V/Y、X293H/I/K/L/N/Q/T/V、X294A/I/V、X295R/S、X296L/N/V/W、X297A、X308F、X311C/T/V、X323C/I/M/T/V、X324L/T、X326V、X328A/G/E、X332V、X353E、およびX356Rから選択される1つの残基の相違をさらに含む、項目1に記載の操作されたポリペプチド。
(項目11)
前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、以下の残基の位置:X29、X137、X157、X184、X197、X198、X201、X220、X232、X261、X266、X279、X280、X287、X288、X293、X295、X311、X324、X328、X332、およびX353に残基の相違を含まない、項目1に記載の操作されたポリペプチド。
(項目12)
前記イミンレダクターゼ活性が、適切な反応条件下での以下のケトン基質化合物およびアミン基質化合物の対のうちの少なくとも1つの、列挙したアミン生成物化合物への変換:
(a)ケトン基質化合物(1j)
およびアミン基質化合物(2b)
のアミン生成物化合物(3o)
への変換、
(b)ケトン基質化合物(1j)
およびアミン基質化合物(2c)
のアミン生成物化合物(3p)
への変換、
(c)ケトン基質化合物(1j)
およびアミン基質化合物(2g)
のアミン生成物化合物(3q)
への変換、
(d)ケトン基質化合物(1i)
およびアミン基質化合物(2h)
のアミン生成物化合物(3r)
への変換、ならびに、
(e)ケトン基質化合物(1e)
およびアミン基質化合物(2d)
のアミン生成物化合物(3s)
への変換
を含む、項目1に記載の操作されたポリペプチド。
(項目13)
適切な反応条件下での前記ケトン基質化合物および前記アミン基質化合物の対の前記列挙したアミン生成物化合物への変換における前記イミンレダクターゼ活性が、対応する配列番号6の参照ポリペプチドの活性と比較した場合に少なくとも2倍に増加する、項目12に記載の操作されたポリペプチド。
(項目14)
前記アミノ酸配列が、配列番号8〜924のうち偶数番号の配列識別子からなる群から選択される配列を含む、項目1に記載の操作されたポリペプチド。
(項目15)
項目1に記載の操作されたポリペプチドをコードするポリヌクレオチド。
(項目16)
前記ポリヌクレオチドが、配列番号7〜923のうち奇数番号の配列識別子からなる群から選択される核酸配列を含む、項目15に記載のポリヌクレオチド。
(項目17)
項目15に記載のポリヌクレオチドを含む発現ベクター。
(項目18)
項目15に記載のポリヌクレオチドを含む宿主細胞。
(項目19)
項目17に記載の発現ベクターを含む宿主細胞。
(項目20)
イミンレダクターゼ活性を有する操作されたポリペプチドを調製する方法であって、項目18に記載の宿主細胞を、ポリペプチドの発現に適切な条件下で培養する工程を含み、任意選択的に、前記操作されたポリペプチドを単離する工程をさらに含む、方法。
(項目21)
イミンレダクターゼ活性を有する操作されたポリペプチドを調製する方法であって、項目19に記載の宿主細胞を、ポリペプチドの発現に適切な条件下で培養する工程を含み、任意選択的に、前記操作されたポリペプチドを単離する工程をさらに含む、方法。
(項目22)
式(III):
(式中、
R 1 基およびR 2 基は、水素原子、ならびに任意選択的に置換されたアルキル、アルケニル、アルキニル、アルコキシ、カルボキシ、アミノカルボニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボキシアルキル、アミノアルキル、ハロアルキル、アルキルチオアルキル、シクロアルキル、アリール、アリールアルキル、ヘテロシクロアルキル、ヘテロアリール、およびヘテロアリールアルキルから独立して選択され;任意選択的にR 1 およびR 2 が連結して3員環から10員環を形成し;
R 3 基およびR 4 基は、水素原子、ならびに任意選択的に置換されたアルキル、アルケニル、アルキニル、アルコキシ、カルボキシ、アミノカルボニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボキシアルキル、アミノアルキル、ハロアルキル、アルキルチオアルキル、シクロアルキル、アリール、アリールアルキル、ヘテロシクロアルキル、ヘテロアリール、およびヘテロアリールアルキルから独立して選択され、但し、R 3 およびR 4 の両方が水素であり得ないことを条件とし;任意選択的に、R 3 およびR 4 が連結して3員環から10員環を形成し;
任意選択的に、 * で示した炭素原子および/または窒素はキラルである)のアミン化合物を調製するためのプロセスであって、
式(I)
(式中、
R 1 およびR 2 は上記定義の通りである)の化合物;
および
式(II)
(式中、
R 3 およびR 4 は上記定義の通りである)の化合物を、
適切な反応条件下にて補因子の存在下でイミンレダクターゼ活性を有する項目1に記載の操作されたポリペプチドと接触させる工程を含む、プロセス。
(項目23)
R 3 およびR 4 が連結して3員環から10員環を形成している、項目22に記載のプロセス。
(項目24)
前記式(II)の基質化合物が、メチルアミン、ジメチルアミン、イソプロピルアミン、ブチルアミン、イソブチルアミン(isobutylaminel)、L−ノルバリン、アニリン、(S)−2−アミノペント−4−エン酸、ピロリジン、およびヒドロキシピロリジンから選択される、項目22に記載のプロセス。
(項目25)
前記式(I)の化合物のR 1 およびR 2 のうちの少なくとも1つが前記式(II)のアミン化合物のR 3 およびR 4 のうちの少なくとも1つに連結しており、それにより、前記式(III)のアミン化合物を調製するためのプロセスが分子内反応を含む、項目22に記載のプロセス。
(項目26)
前記適切な反応条件が、以下:
(a)約10g/L〜100g/Lの基質負荷;
(b)約0.1g/L〜約50g/Lの前記操作されたポリペプチド;
(c)約0.05g/L(0.001M)〜約2.5g/L(0.050M)のNAD(P)H;
(d)約6〜10のpH;
(e)約20℃〜50℃の温度;および
(f)2〜120時間の反応時間
を含む、項目22に記載のプロセス。
本明細書中および添付の特許請求の範囲で使用する場合、文脈上明らかに他の意味を示さない限り、単数形「a」、「an」、および「the」には、複数の指示対象が含まれる。したがって、例えば、「a polypeptide」という表記には1つを超えるポリペプチドが含まれる。同様に、「comprise」、「comprises」、「comprising」「include」、「includes」、および「including」は、相互に交換可能であり、本発明を制限することを意図しない。種々の実施形態の説明で用語「comprising」を使用する場合、当業者は、いくつかの特定の例では、「consisting essentially of」または「consisting of」という用語を使用して実施形態を代わりに説明することができると理解すべきである。種々の実施形態の説明で用語「任意選択的な」または「任意選択的に」を使用する場合、その後に記載する事象または状況が起こっても起こらなくてもよく、この記載には事象または状況が起こる場合および起こらない例が含まれるとさらに理解すべきである。前述の一般的な説明および以下の詳細な説明の両方は例示および説明のみを目的とし、本発明を制限しないと理解すべきである。本明細書中で使用した節の表題は、まとめのみを目的とし、記載の主題を制限すると解釈されない。
略語:
定義:
6.3 操作されたイミンレダクターゼ(IRED)ポリペプチド
(i)配列番号6の参照配列と比較した場合に、X12、X18、X26、X27、X57、X65、X87、X93、X96、X126、X138、X140、X142、X159、X170、X175、X177、X195、X200、X221、X234、X241、X242、X253、X254、X257、X262、X263、X267、X272、X276、X277、X278、X281、X282、X291、およびX352から選択される位置での1つの残基の相違であって、任意選択的に、前記位置での残基の相違が、X12M、X18G、X26M/V、X27S、X57D/L/V、X65I/V、X87A、X93G/Y、X96C、X126S、X138L、X140M、X142A、X159C/L/Q/V、X170F/K/R/S、X175R、X177R、X195S、X200S、X221F、234C/L、X241K、X242C/L、X253K/N、X254R、X257Q、X262F/G/P/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X267E/G/H/I/N/S、X272D、X276L、X277H/L、X278E/H/K/N/R/S/W、X281A、X282A/R、X291E、およびX352Qから選択される、1つの残基の相違;
(ii)配列番号6の参照配列と比較した場合に、X20V、X29K、X37P、X74W、X82C/T、X94N、X108S、X111A/H、X141M/N、X143F/L/Y、X153E/F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X163V、X197V、X201I、X220C/K/Q、X223S、X256A/E/I/L/S/T、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X264V、X270L、X273C、X274L/S、X279T、X284C/F/H/P/Q/S、X292E/P、およびX295Fから選択される1つの残基の相違;および/または
(iii)配列番号6の参照配列と比較した場合に、X82P、X141W、X153Y、X154F、X259I/L/M、X274L/M、X283V、およびX296N/Vから選択される2つまたはそれを超える残基の相違を有するアミノ酸配列を含む。
(a)基質化合物(1a)および(2a)の生成物化合物(3a)への変換;
(b)基質化合物(1a)および(2b)の生成物化合物(3b)への変換;
(c)基質化合物(1b)および(2a)の生成物化合物(3c)への変換;
(d)基質化合物(1b)および(2b)の生成物化合物(3d)への変換;
(e)基質化合物(1b)および(2c)の生成物化合物(3e)への変換;
(f)基質化合物(1b)および(2d)の生成物化合物(3f)への変換;
(g)基質化合物(1c)および(2a)の生成物化合物(3g)への変換;
(h)基質化合物(1d)および(2a)の生成物化合物(3h)への変換;
(i)基質化合物(1e)および(2b)の生成物化合物(3i)への変換;
(j)基質化合物(1f)および(2b)の生成物化合物(3j)への変換;
(k)基質化合物(1g)および(2e)の生成物化合物(3k)への変換;
(l)基質化合物(1b)および(2f)の生成物化合物(3l)への変換;
(m)基質化合物(1h)および(2a)の生成物化合物(3m)への変換;
(n)基質化合物(1i)および(2b)の生成物化合物(3n)への変換;
(o)基質化合物(1j)および(2b)の生成物化合物(3o)への変換;
(p)基質化合物(1j)および(2c)の生成物化合物(3p)への変換;
(q)基質化合物(1j)および(2g)の生成物化合物(3q)への変換;
(r)基質化合物(1i)および(2h)の生成物化合物(3r)への変換;および
(s)基質化合物(1e)および(2d)の生成物化合物(3s)への変換。
6.4 操作されたイミンレダクターゼをコードするポリヌクレオチド、発現ベクター、および宿主細胞
(i)配列番号6の参照配列と比較した場合に、X12、X18、X26、X27、X57、X65、X87、X93、X96、X126、X138、X140、X142、X159、X170、X175、X177、X195、X200、X221、X234、X241、X242、X253、X254、X257、X262、X263、X267、X272、X276、X277、X278、X281、X282、X291、およびX352から選択される位置での1つの残基の相違であって、任意選択的に、前記位置での残基の相違が、X12M、X18G、X26M/V、X27S、X57D/L/V、X65I/V、X87A、X93G/Y、X96C、X126S、X138L、X140M、X142A、X159C/L/Q/V、X170F/K/R/S、X175R、X177R、X195S、X200S、X221F、234C/L、X241K、X242C/L、X253K/N、X254R、X257Q、X262F/G/P/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X267E/G/H/I/N/S、X272D、X276L、X277H/L、X278E/H/K/N/R/S/W、X281A、X282A/R、X291E、およびX352Qから選択される、1つの残基の相違;
(ii)配列番号6の参照配列と比較した場合に、X20V、X29K、X37P、X74W、X82C/T、X94N、X108S、X111A/H、X141M/N、X143F/L/Y、X153F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X163V、X197V、X201I、X220C/K/Q、X223S、X256A/E/I/L/S/T、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X264V、X270L、X273C、X274L/S、X279T、X284C/F/H/P/Q/S、X292E/P、およびX295Fから選択される1つの残基の相違;および/または
(iii)配列番号6の参照配列と比較した場合に、X82P、X141W、X153Y、X154F、X259I/L/M、X274L/M、X283V、およびX296N/Vから選択される2つまたはそれを超える残基の相違のうちの少なくとも1つを有するアミノ酸配列を含む。いくつかの実施形態では、参照配列は、配列番号6、12、84、92、146、162、198、228、250、354、および440から選択される。
of St.Louis MOのCelLytic B(商標)など)。イミンレダクターゼポリペプチドの単離のためのクロマトグラフィ技術には、とりわけ、逆相クロマトグラフィ、高速液体クロマトグラフィ、イオン交換クロマトグラフィ、ゲル電気泳動、およびアフィニティクロマトグラフィが含まれる。
6.5 操作されたイミンレダクターゼ酵素の使用方法
(i)配列番号6の参照配列と比較した場合に、X12、X18、X26、X27、X57、X65、X87、X93、X96、X126、X138、X140、X142、X159、X170、X175、X177、X195、X200、X221、X234、X241、X242、X253、X254、X257、X262、X263、X267、X272、X276、X277、X278、X281、X282、X291、およびX352から選択される位置における1つの残基の相違であって、任意選択的に、前記位置における残基の相違が、X12M、X18G、X26M/V、X27S、X57D/L/V、X65I/V、X87A、X93G/Y、X96C、X126S、X138L、X140M、X142A、X159C/L/Q/V、X170F/K/R/S、X175R、X177R、X195S、X200S、X221F、234C/L、X241K、X242C/L、X253K/N、X254R、X257Q、X262F/G/P/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X267E/G/H/I/N/S、X272D、X276L、X277H/L、X278E/H/K/N/R/S/W、X281A、X282A/R、X291E、およびX352Qから選択される、1つの残基の相違;
(ii)配列番号6の参照配列と比較した場合に、X20V、X29K、X37P、X74W、X82C/T、X94N、X108S、X111A/H、X141M/N、X143F/L/Y、X153E/F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X163V、X197V、X201I、X220C/K/Q、X223S、X256A/E/I/L/S/T、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X264V、X270L、X273C、X274L/S、X279T、X284C/F/H/P/Q/S、X292E/P、およびX295Fから選択される1つの残基の相違;および/または
(iii)配列番号6の参照配列と比較した場合に、X82P、X141W、X153Y、X154F、X259I/L/M、X274L/M、X283V、およびX296N/Vから選択される2つまたはそれを超える残基の相違のうちの少なくとも1つを有するアミノ酸配列を含む操作されたイミンレダクターゼポリペプチドを使用することができる。
実験
以下に開示の実験では、以下の略語を適用する:ppm(百万分率);M(モル濃度);mM(ミリモル濃度)、uMおよびμM(マイクロモル濃度);nM(ナノモル濃度);mol(モル);gmおよびg(グラム);mg(ミリグラム);ugおよびμg(マイクログラム);Lおよびl(リットル);mlおよびmL(ミリリットル);cm(センチメートル);mm(ミリメートル);umおよびμm(マイクロメートル);sec.(秒);min(分);hおよびhr(時間);U(ユニット);MW(分子量);rpm(毎分回転数);psiおよびPSI(ポンド/平方インチ);℃(摂氏);RTおよびrt(室温);CAMおよびcam(クロラムフェニコール);DMSO(ジメチルスルホキシド);PMBS(硫酸ポリミキシンB);IPTG(イソプロピルβ−D−1−チオガラクトピラノシド);LB(Luriaブロス);TB(terrificブロス);SFP(フラスコ振盪培養粉末);CDS(コード配列);DNA(デオキシリボ核酸);RNA(リボ核酸);大腸菌W3110(一般的に使用される研究用大腸菌株,the Coli Genetic Stock Center[CGSC],New Haven,CTから利用可能);HTP(高処理);HPLC(高圧液体クロマトグラフィ);FIOPC(ポジティブコントロールに対する改良の倍数);Sigma−Aldrich(Sigma−Aldrich,St.Louis,MO;Difco(Difco Laboratories,BD Diagnostic Systems,Detroit,MI);Agilent(Agilent Technologies,Inc.,Santa Clara,CA);Corning(Corning,Inc.,Palo Alto,CA);Dow Corning(Dow Corning,Corp.,Midland,MI);およびGene Oracle(Gene Oracle,Inc.,Mountain View,CA)。
イミンレダクターゼ活性を有するCENDHから誘導された操作されたポリペプチドの合成、最適化、およびスクリーニング
遺伝子の合成および最適化:配列番号2に示すArthrobacter sp.C1株由来の報告された野生型オピンデヒドロゲナーゼポリペプチドCENDHをコードするポリヌクレオチド配列を、GeneIOS合成プラットフォーム(GeneOracle)を使用してコドン最適化し、配列番号1の遺伝子として合成した。配列番号1の合成遺伝子を、pCK110900ベクター系(例えば、米国特許出願公開第20060195947号(本明細書中で参照によって組み込まれる)を参照のこと)にクローン化し、その後に大腸菌W3110fhuA中で発現させた。大腸菌W3110株は、lacプロモーターの調節下でオピンデヒドロゲナーゼポリペプチドCENDHを発現した。他のCENDH(および他のアミノ酸デヒドロゲナーゼ)および基質にドッキングしたCENDH構造のコンピュータモデリングを使用した配列比較に基づいて、活性部位、ペプチドループ、溶液/基質界面、および潜在的な安定性のある位置に関連する残基の位置を同定した。
実施例2
イミンレダクターゼ活性を有するCENDHから誘導された操作されたポリペプチドの生成
実施例3
化合物(3n)、(3o)、(3p)、(3q)、(3r)、および(3s)の調製における改良された安定性およびイミンレダクターゼ活性についての配列番号6から誘導された操作されたポリペプチドの進化およびスクリーニング
Claims (28)
- 操作されたポリペプチドであって、配列番号6の参照配列と少なくとも90%の配列同一性を有するアミノ酸配列を含み、前記アミノ酸配列が:
(i)配列番号6の前記参照配列と比較した場合の1つの残基の相違であって、前記残基の相違が、X263C/D/E/H/I/K/L/M/N/P/Q/Vである、1つの残基の相違;
を含み、
前記操作されたポリペプチドが、配列番号6のポリペプチドと比較した場合に、少なくとも1.2倍のイミンレダクターゼ活性を有する、操作されたポリペプチド。 - 前記アミノ酸配列がさらに、以下の特徴:
(ii)配列番号6の前記参照配列と比較した場合に、X20V、X29K、X37P、X74W、X82C/T、X94N、X108S、X111A/H、X141M/N、X143F/L/Y、X153E/F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X163V、X197V、X201I、X220C/K/Q、X223S、X256A/E/I/L/S/T、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X264V、X270L、X273C、X274L/S、X279T、X284C/F/H/P/Q/S、X292E/P、およびX295Fから選択される1つの残基の相違;および/または
(iii)配列番号6の前記参照配列と比較した場合に、X153Y、X283V、X82P、X141W、X154F、X259I/L/M、X274L/M、およびX296N/Vから選択される2つまたはそれを超える残基の相違;
のうち少なくとも1つを含む、請求項1に記載の操作されたポリペプチド。 - 前記アミノ酸配列がさらに、配列番号6と比較した場合に、R111A、T141W、N153Y、A154F、C256E、V274M、I283V、M284SおよびE296Nの残基の相違を含む、請求項1に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X12M、X37P、X82T、X111A、X154S、X156N/M、X223S、X256E、X260D、X261H、X262P、X263C/E/Q、X267G、X277L、X281A、X284P/S、およびX292Eから選択される少なくとも1つの残基の相違を含む、請求項1に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X256E、X93G/Y、X94N、X96C、X111A/H、X142A、X159L、X163V、X259R、X273C、およびX284P/Sから選択される少なくとも1つの残基の相違を含む、請求項1に記載の操作されたポリペプチド。
- 前記アミノ酸配列は、配列番号6の前記参照配列と比較した場合に、X82C/P/T、X141W、X143W、X153Y、X154F/Q/Y、X256V、X259I/L/M/T、X260G、X261R、X265L、X273W、X274M、X277A/I、X279L、X283V、X284L、X296N、X326Vから選択される少なくとも2つの残基の相違を含む、請求項1に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、以下:
(a)X153Y、およびX283V;
(b)X141W、X153Y、およびX283V;
(c)X141W、X153Y、X274L/M、およびX283V;
(d)X141W、X153Y、X154F、X274L/M、およびX283V;
(e)X141W、X153Y、X154F、およびX283V;
(f)X141W、X153Y、X283V、およびX296N/V;
(g)X141W、X153Y、X274L/M、X283V、およびX296N/V:(h)X111A、X153Y、X256E、X274M、およびX283V;
(i)X111A、X141W、X153Y、X273C、X274M、X283V、およびX284S;
(j)X111A、X141W、X153Y、X273C、およびX283V;
(k)X111A、X141W、X153Y、X154F、X256E、X274M、X283V、X284S、およびX296N;
(l)X111A、X141W、X153Y、X256E、X273W、X274L、X283V、X284S、およびX296N;
(m)X111H、X141W、X153Y、X273W、X274M、X284S、およびX296N;
(n)X111H、X141W、X153Y、X154F、X273W、X274L、X283V、X284S、およびX296N;
(o)X82P、X141W、X153Y、X256E、X274M、およびX283V;
(p)X82P、X111A、X141W、X153Y、X256E、X274M、X283V、M284S、およびE296V;
(q)X94N、X143W、X159L、X163V、X259M、およびX279L;
(r)X141W、X153Y、X154F、およびX256E;および
(s)X153Y、X256E、およびX274M
から選択される残基の相違の少なくとも1つの組み合わせを含む、請求項1に記載の操作されたポリペプチド。 - 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X12M、X18G、X20V、X26M/V、X27S、X29K、X37P、X57D/L/V、X65I/V、X74W、X82C/T、X87A、X93G/Y、X94N、X96C、X108S、X111A/H、X126S、X138L、X140M、X141M/N、X142A、X143F/L/Y、X153E/F、X154C/D/G/K/L/N/S/T/V、X156H/L/N/M/R、X157F/Q/T/Y、X158I/L/R/S/T/V、X159C/L/Q/V、X163V、X170F/K/R/S、X175R、X177R、X195S、X197V、X200S、X201I、X220C/K/Q、X221F、X223S、X234V/C/L、X241K、X242C/L、X253K/N、X254R、X256A/E/I/L/S/T、X257Q、X259C/R、X260A/D/N/Q/V/Y、X261E/F/H/L/P/Q/Y、X262P、X262F/G/V、X263C/D/E/H/I/K/L/M/N/P/Q/V、X264V、X267E/G/H/I/N/S、X270L、X272D、X273C、X274L/S、X276L、X277H/L、X278E/H/K/N/R/S/W、X279T、X281A、X282A/R、X284C/F/H/P/Q/S、X291E、X292E/P、X295F、およびX352Qから選択される少なくとも1つの残基の相違をさらに含む、請求項7に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X12M、X37P、X82T、X111A、X141W、X153Y、X154F/S、X156N/M、X223S、X256E、X259I、X260D、X261H、X262P、X263C/E/Q、X267G、X274M、X277L、X281A、X283V、X284P/S、X292E、およびX296Nから選択される少なくとも1つの残基の相違をさらに含む、請求項7に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、残基の相違X111A、X141W、X153Y、X154F、X256E、X274M、X283V、X284S、およびX296N、ならびに以下:
(a)X156N;
(b)X37P、X82T、およびX156N;
(c)X37P、X82T、X156N、およびX259I;
(d)X259L/M;
(e)X82T、X156N、X223S、X259L、X267G、およびX281A;
(f)X263C;
(g)X12M、X261H、X263C、X277L、およびX292E;
(h)X154S;および
(i)X154S、X156M、X260D、X261H、X262P、X263E、およびX284P
から選択される少なくとも1つの残基の相違または残基の相違の組み合わせを含む、請求項1に記載の操作されたポリペプチド。 - 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X29、X137、X157、X184、X197、X198、X201、X220、X232、X261、X266、X279、X280、X287、X288、X293、X295、X311、X324、X328、X332、およびX353から選択される残基の位置に残基の相違を含まない、請求項1に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、X4H/L/R、X5T、X14P、X20T、X29R/T、X37H、X67A/D、X71C/V、X74R、X82P、X94K/R/T、X97P、X100W、X111M/Q/R/S、X124L/N、X136G、X137N、X141W、X143W、X149L、X153E/V/Y、X154F/M/Q/Y、X156G/I/Q/S/T/V、X157D/H/L/M/N/R、X158K、X160N、X163T、X177C/H、X178E、X183C、X184K/Q/R、X185V、X186K/R、X197I/P、X198A/E/H/P/S、X201L、X220D/H、X223T、X226L、X232G/A/R、X243G、X246W、X256V、X258D、X259E/H/I/L/M/S/T/V/W、X260G、X261A/G/I/K/R/S/T、X265G/L/Y、X266T、X270G、X273W、X274M、X277A/I、X279F/L/V/Y、X280L、X283M/V、X284K/L/M/Y、X287S/T、X288G/S、X292C/G/I/P/S/T/V/Y、X293H/I/K/L/N/Q/T/V、X294A/I/V、X295R/S、X296L/N/V/W、X297A、X308F、X311C/T/V、X323C/I/M/T/V、X324L/T、X326V、X328A/G/E、X332V、X353E、およびX356Rから選択される1つの残基の相違をさらに含む、請求項1に記載の操作されたポリペプチド。
- 前記アミノ酸配列が、配列番号6の前記参照配列と比較した場合に、以下の残基の位置:X29、X137、X157、X184、X197、X198、X201、X220、X232、X261、X266、X279、X280、X287、X288、X293、X295、X311、X324、X328、X332、およびX353に残基の相違を含まない、請求項1に記載の操作されたポリペプチド。
- 前記イミンレダクターゼ活性が、適切な反応条件下での以下のケトン基質化合物およびアミン基質化合物の対のうちの少なくとも1つの、列挙したアミン生成物化合物への変換:
(a)ケトン基質化合物(1j)
(b)ケトン基質化合物(1j)
(c)ケトン基質化合物(1j)
(d)ケトン基質化合物(1i)
(e)ケトン基質化合物(1e)
を含む、請求項1に記載の操作されたポリペプチド。 - 適切な反応条件下での前記ケトン基質化合物および前記アミン基質化合物の対の前記列挙したアミン生成物化合物への変換における前記イミンレダクターゼ活性が、対応する配列番号6の参照ポリペプチドの活性と比較した場合に少なくとも2倍に増加する、請求項14に記載の操作されたポリペプチド。
- 配列番号8〜924のうち偶数番号の配列識別子からなる群から選択されるアミノ酸配列を含む、操作されたポリペプチド。
- 請求項1に記載の操作されたポリペプチドをコードするポリヌクレオチド。
- 配列番号7〜923のうち奇数番号の配列識別子からなる群から選択される核酸配列を含む、ポリヌクレオチド。
- 請求項17または18に記載のポリヌクレオチドを含む発現ベクター。
- 請求項17または18に記載のポリヌクレオチドを含む宿主細胞。
- 請求項19に記載の発現ベクターを含む宿主細胞。
- イミンレダクターゼ活性を有する操作されたポリペプチドを調製する方法であって、請求項20に記載の宿主細胞を、ポリペプチドの発現に適切な条件下で培養する工程を含み、任意選択的に、前記操作されたポリペプチドを単離する工程をさらに含む、方法。
- イミンレダクターゼ活性を有する操作されたポリペプチドを調製する方法であって、請求項21に記載の宿主細胞を、ポリペプチドの発現に適切な条件下で培養する工程を含み、任意選択的に、前記操作されたポリペプチドを単離する工程をさらに含む、方法。
- 式(III):
R1基およびR2基は、水素原子、ならびに任意選択的に置換されたアルキル、アルケニル、アルキニル、アルコキシ、カルボキシ、アミノカルボニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボキシアルキル、アミノアルキル、ハロアルキル、アルキルチオアルキル、シクロアルキル、アリール、アリールアルキル、ヘテロシクロアルキル、ヘテロアリール、およびヘテロアリールアルキルから独立して選択され;任意選択的にR1およびR2が連結して3員環から10員環を形成し;
R3基およびR4基は、水素原子、ならびに任意選択的に置換されたアルキル、アルケニル、アルキニル、アルコキシ、カルボキシ、アミノカルボニル、ヘテロアルキル、ヘテロアルケニル、ヘテロアルキニル、カルボキシアルキル、アミノアルキル、ハロアルキル、アルキルチオアルキル、シクロアルキル、アリール、アリールアルキル、ヘテロシクロアルキル、ヘテロアリール、およびヘテロアリールアルキルから独立して選択され、但し、R3およびR4の両方が水素であり得ないことを条件とし;任意選択的に、R3およびR4が連結して3員環から10員環を形成し;
任意選択的に、*で示した炭素原子および/または窒素はキラルである)のアミン化合物を調製するためのプロセスであって、
式(I)
R1およびR2は上記定義の通りである)の化合物;
および
式(II)
R3およびR4は上記定義の通りである)の化合物を、
適切な反応条件下にて補因子の存在下でイミンレダクターゼ活性を有する請求項1に記載の操作されたポリペプチドと接触させる工程を含む、プロセス。 - R3およびR4が連結して3員環から10員環を形成している、請求項24に記載のプロセス。
- 前記式(II)の基質化合物が、メチルアミン、ジメチルアミン、イソプロピルアミン、ブチルアミン、イソブチルアミン(isobutylaminel)、L−ノルバリン、アニリン、(S)−2−アミノペント−4−エン酸、ピロリジン、およびヒドロキシピロリジンから選択される、請求項24に記載のプロセス。
- 前記式(I)の化合物のR1およびR2のうちの少なくとも1つが前記式(II)のアミン化合物のR3およびR4のうちの少なくとも1つに連結しており、それにより、前記式(III)のアミン化合物を調製するためのプロセスが分子内反応を含む、請求項24に記載のプロセス。
- 前記適切な反応条件が、以下:
(a)10g/L〜100g/Lの基質負荷;
(b)0.1g/L〜50g/Lの前記操作されたポリペプチド;
(c)0.05g/L(0.001M)〜2.5g/L(0.050M)のNAD(P)H;
(d)6〜10のpH;
(e)20℃〜50℃の温度;および
(f)2〜120時間の反応時間
を含む、請求項24に記載のプロセス。
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---|---|---|---|---|
ES2730684T3 (es) * | 2009-12-17 | 2019-11-12 | Pioneer Hi Bred Int | Evento de maíz DP-004114-3 y métodos para la detección del mismo |
JP6643987B2 (ja) | 2013-11-13 | 2020-02-12 | コデクシス, インコーポレイテッド | ケトン化合物およびアミン化合物の還元的アミノ化のための操作されたイミンレダクターゼおよび方法 |
JP6719463B2 (ja) | 2014-11-25 | 2020-07-15 | コデクシス, インコーポレイテッド | ケトン化合物およびアミン化合物の還元的アミノ化のための操作されたイミンレダクターゼおよび方法 |
KR101761830B1 (ko) | 2015-10-21 | 2017-07-26 | 주식회사 엘지화학 | 리간드 화합물, 올레핀 올리고머화용 촉매계, 및 이를 이용한 올레핀 올리고머화 방법 |
JP7316662B2 (ja) * | 2016-08-26 | 2023-07-28 | コデクシス, インコーポレイテッド | 操作されたイミンレダクターゼ、ならびにケトン化合物およびアミン化合物の還元的アミノ化のための方法 |
CN107384885B (zh) * | 2017-09-05 | 2019-12-24 | 武汉大学 | 亚胺还原酶及其突变体在合成(s)-1-芳基-1,2,3,4-四氢异喹啉中的应用 |
CN108504701B (zh) * | 2018-04-26 | 2021-05-14 | 中南林业科技大学 | 一种异丙甲草胺中间体的合成方法 |
HUE051799T2 (hu) | 2018-11-16 | 2021-03-29 | Zanoprima Lifesciences Ltd | Eljárás (S)-nikotin elõállítására myosmine vegyületbõl |
CA3136828A1 (en) * | 2019-05-01 | 2020-11-05 | Codexis, Inc. | Engineered imine reductases and methods for the reductive amination of ketone and amine compounds |
CN114717211B (zh) * | 2022-03-23 | 2023-06-02 | 江苏集萃分子工程研究院有限公司 | 亚胺还原酶突变体m5及其在合成氮杂环手性胺中的应用 |
Family Cites Families (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5538867A (en) | 1988-09-13 | 1996-07-23 | Elf Aquitaine | Process for the electrochemical regeneration of pyridine cofactors |
KR100356926B1 (ko) | 1993-09-07 | 2003-01-10 | 교와 핫꼬 고교 가부시끼가이샤 | 트랜스-4-히드록시-l-프롤린의제조법 |
US6395547B1 (en) | 1994-02-17 | 2002-05-28 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US5834252A (en) | 1995-04-18 | 1998-11-10 | Glaxo Group Limited | End-complementary polymerase reaction |
US20060257890A1 (en) | 1996-05-20 | 2006-11-16 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
US6117679A (en) | 1994-02-17 | 2000-09-12 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US5928905A (en) | 1995-04-18 | 1999-07-27 | Glaxo Group Limited | End-complementary polymerase reaction |
US6406855B1 (en) | 1994-02-17 | 2002-06-18 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
US6165793A (en) | 1996-03-25 | 2000-12-26 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US6995017B1 (en) | 1994-02-17 | 2006-02-07 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US6335160B1 (en) | 1995-02-17 | 2002-01-01 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
US6309883B1 (en) | 1994-02-17 | 2001-10-30 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
ATE206460T1 (de) | 1994-06-03 | 2001-10-15 | Novo Nordisk Biotech Inc | Gereinigte myceliophthora laccasen und nukleinsäuren dafür kodierend |
ATE294871T1 (de) | 1994-06-30 | 2005-05-15 | Novozymes Biotech Inc | Nicht-toxisches, nicht-toxigenes, nicht- pathogenes fusarium expressionssystem und darin zu verwendende promotoren und terminatoren |
FI104465B (fi) | 1995-06-14 | 2000-02-15 | Valio Oy | Proteiinihydrolysaatteja allergioiden hoitamiseksi tai estämiseksi, niiden valmistus ja käyttö |
US6096548A (en) | 1996-03-25 | 2000-08-01 | Maxygen, Inc. | Method for directing evolution of a virus |
US6506602B1 (en) | 1996-03-25 | 2003-01-14 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US6326204B1 (en) | 1997-01-17 | 2001-12-04 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
US7148054B2 (en) | 1997-01-17 | 2006-12-12 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
EP1007732B1 (en) | 1997-01-17 | 2006-07-26 | Maxygen, Inc. | EVOLUTION OF procaryotic WHOLE CELLS BY RECURSIVE SEQUENCE RECOMBINATION |
DK1036198T3 (da) | 1997-12-08 | 2013-01-02 | California Inst Of Techn | Fremgangsmåde til fremstilling af polynukleotid- og polypeptidsekvenser |
US6365408B1 (en) | 1998-06-19 | 2002-04-02 | Maxygen, Inc. | Methods of evolving a polynucleotides by mutagenesis and recombination |
US6495023B1 (en) | 1998-07-09 | 2002-12-17 | Michigan State University | Electrochemical methods for generation of a biological proton motive force and pyridine nucleotide cofactor regeneration |
JP4221100B2 (ja) | 1999-01-13 | 2009-02-12 | エルピーダメモリ株式会社 | 半導体装置 |
US6917882B2 (en) | 1999-01-19 | 2005-07-12 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
US6436675B1 (en) | 1999-09-28 | 2002-08-20 | Maxygen, Inc. | Use of codon-varied oligonucleotide synthesis for synthetic shuffling |
US6368861B1 (en) | 1999-01-19 | 2002-04-09 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
US6376246B1 (en) | 1999-02-05 | 2002-04-23 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
US7024312B1 (en) | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
US7702464B1 (en) | 2001-08-21 | 2010-04-20 | Maxygen, Inc. | Method and apparatus for codon determining |
DE60044223D1 (de) | 1999-01-19 | 2010-06-02 | Maxygen Inc | Durch oligonukleotide-vermittelte nukleinsäuren-rekombination |
US6961664B2 (en) | 1999-01-19 | 2005-11-01 | Maxygen | Methods of populating data structures for use in evolutionary simulations |
EP1165775A2 (en) | 1999-03-05 | 2002-01-02 | Maxygen, Inc. | Recombination of insertion modified nucleic acids |
AU3874900A (en) | 1999-03-11 | 2000-09-28 | Eastman Chemical Company | Enzymatic reductions with dihydrogen via metal catalyzed cofactor regeneration |
US7430477B2 (en) | 1999-10-12 | 2008-09-30 | Maxygen, Inc. | Methods of populating data structures for use in evolutionary simulations |
US6519065B1 (en) | 1999-11-05 | 2003-02-11 | Jds Fitel Inc. | Chromatic dispersion compensation device |
EP1272967A2 (en) | 2000-03-30 | 2003-01-08 | Maxygen, Inc. | In silico cross-over site selection |
EP1479762B1 (en) | 2002-02-28 | 2011-09-28 | Mitsubishi Chemical Corporation | Novel dehydrogenase and gene encoding the same |
US7747391B2 (en) | 2002-03-01 | 2010-06-29 | Maxygen, Inc. | Methods, systems, and software for identifying functional biomolecules |
DK2315145T3 (en) | 2002-03-01 | 2016-01-25 | Codexis Mayflower Holdings Llc | Methods, systems, and software for identifying the functional biomolecules |
US20050084907A1 (en) | 2002-03-01 | 2005-04-21 | Maxygen, Inc. | Methods, systems, and software for identifying functional biomolecules |
EP1488335A4 (en) | 2002-03-09 | 2006-11-15 | Maxygen Inc | OPTIMIZING CROSSOVER POINTS FOR THE ADJUSTED EVOLUTION |
US7824898B2 (en) | 2003-08-11 | 2010-11-02 | Codexis, Inc. | Halohydrin dehalogenases and related polynucleotides |
MXPA06001719A (es) | 2003-08-11 | 2006-05-19 | Codexis Inc | Polipeptidos de glucosa deshidrogenasa mejorados, y polinucleotidos relacionados. |
EP1654354A1 (en) | 2003-08-11 | 2006-05-10 | Codexis, Inc. | Improved ketoreductase polypeptides and related polynucleotides |
AU2004266100A1 (en) | 2003-08-11 | 2005-03-03 | Codexis, Inc. | Enzymatic processes for the production of 4-substituted 3-hydroxybutyric acid derivatives and vicinal cyano, hydroxy substituted carboxylic acid esters |
KR101502634B1 (ko) | 2007-02-08 | 2015-03-16 | 코덱시스, 인코포레이티드 | 케토 환원 효소 및 이의 용도 |
US20090118130A1 (en) | 2007-02-12 | 2009-05-07 | Codexis, Inc. | Structure-activity relationships |
US7977078B2 (en) | 2007-08-24 | 2011-07-12 | Codexis, Inc. | Ketoreductase polypeptides for the production of (R)-3-hydroxythiolane |
WO2009036404A2 (en) | 2007-09-13 | 2009-03-19 | Codexis, Inc. | Ketoreductase polypeptides for the reduction of acetophenones |
EP2203557B1 (en) | 2007-09-28 | 2012-02-29 | Codexis, Inc. | Ketoreductase polypeptides and uses thereof |
EP2205727B1 (en) | 2007-10-01 | 2015-06-24 | Codexis, Inc. | Ketoreductase polypeptides for the production of azetidinone |
PL2285808T3 (pl) | 2008-04-29 | 2014-04-30 | Novartis Ag | Spiro-indolowe pochodne do leczenia chorób pasożytniczych |
US20090312196A1 (en) | 2008-06-13 | 2009-12-17 | Codexis, Inc. | Method of synthesizing polynucleotide variants |
HUE029228T2 (en) | 2008-06-13 | 2017-02-28 | Codexis Inc | A method for the synthesis of polynucleotide variants |
US8426178B2 (en) | 2008-08-27 | 2013-04-23 | Codexis, Inc. | Ketoreductase polypeptides for the production of a 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
US8288141B2 (en) | 2008-08-27 | 2012-10-16 | Codexis, Inc. | Ketoreductase polypeptides for the production of 3-aryl-3-hydroxypropanamine from a 3-aryl-3-ketopropanamine |
WO2010027710A2 (en) | 2008-08-27 | 2010-03-11 | Codexis, Inc. | Ketoreductase polypeptides and uses thereof |
EP2329014B1 (en) | 2008-08-29 | 2014-10-22 | Codexis, Inc. | Ketoreductase polypeptides for the stereoselective production of (4s)-3[(5s)-5(4-fluorophenyl)-5-hydroxypentanoyl]-4-phenyl-1,3-oxazolidin-2-one |
JPWO2010024444A1 (ja) * | 2008-09-01 | 2012-01-26 | ダイセル化学工業株式会社 | 光学活性なアミン誘導体の製造方法 |
WO2010024445A1 (ja) * | 2008-09-01 | 2010-03-04 | ダイセル化学工業株式会社 | 光学活性なアミン誘導体を製造するための方法 |
WO2013170050A1 (en) | 2012-05-11 | 2013-11-14 | Codexis, Inc. | Engineered imine reductases and methods for the reductive amination of ketone and amine compounds |
JP6643987B2 (ja) | 2013-11-13 | 2020-02-12 | コデクシス, インコーポレイテッド | ケトン化合物およびアミン化合物の還元的アミノ化のための操作されたイミンレダクターゼおよび方法 |
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