JP2021530980A - 操作されたデオキシリボースリン酸アルドラーゼ - Google Patents
操作されたデオキシリボースリン酸アルドラーゼ Download PDFInfo
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- JP2021530980A JP2021530980A JP2021500435A JP2021500435A JP2021530980A JP 2021530980 A JP2021530980 A JP 2021530980A JP 2021500435 A JP2021500435 A JP 2021500435A JP 2021500435 A JP2021500435 A JP 2021500435A JP 2021530980 A JP2021530980 A JP 2021530980A
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- Prior art keywords
- phosphate aldolase
- engineered
- sequence
- deoxyribose phosphate
- polypeptide
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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
- C12N9/88—Lyases (4.)
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P21/00—Preparation of peptides or proteins
- C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Y—ENZYMES
- C12Y401/00—Carbon-carbon lyases (4.1)
- C12Y401/02—Aldehyde-lyases (4.1.2)
- C12Y401/02004—Deoxyribose-phosphate aldolase (4.1.2.4)
-
- 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
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Enzymes And Modification Thereof (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
発明の分野
本発明は、医薬化合物およびファインケミカル化合物の生成のための工業プロセス条件下で有用な操作されたデオキシリボースリン酸アルドラーゼポリペプチドを提供する。
配列表の公式の写しを、作成日2019年6月27日およびサイズ832キロバイトのファイル名「CX2−173WO2_ST25.txt」のASCIIフォーマットのテキストファイルとして本明細書と共に、ここに、EFS−Webを介して提出する。EFS−Webを介して提出された配列表は、本明細書の一部であり、その全体が参照によって本明細書に組み込まれる。
235T/S236D、S2C/M47V/A71V/L88A/V203I/S235T/S236D、S2C/M47V/A71V/T141S/F197M/S235T/S236D、S2N、S2R/K6H/R10Q/P66L/L88A/D102E/M184I/S235T/S236D、S2R/K6H/D102E/T141S/V203I/S235T、S2R/R10Q/D102E/S235T/S236D、S2R/L88A/T141S/S235D/S236D、S2R/V203I/S235T/S236D、K5R、K6H/V203I/S235T/S236D、Q9K、Q9L、R10Q/M47V/P66L/M184I/F197M/S236D、R10Q/M47V/P66L/S235T/S236D、R10Q/M47V/A71V/M184I/V203I/S235T/S236D、S13I、S13I/I46V、S13I/I46V/P66S/V94L、S13I/I46V/P66S/V94L/M184V/K204T、S13I/I46V/P66S/T133L/I134L/M184V、S13I/I46V/P66S/M184V、S13I/I46V/E112K/I134L/M184V、S13I/I46V/T133L/M184V、S13I/I46V/T133M/M184V、S13I/P66S/V94L、S13I/P66S/V94L/M184V、S13I/P66S/E112K/T133M/I134L/M184V/K204T、S13I/P66S/E112K/T133M/I134L/K204T、S13I/P66S/E112M/M184V、S13I/P66S/T133M/I134L/M184V/K204T、S13I/P66S/M184V/K204T、S13I/V94L/T133M/M184V、S13I/V94L/M184V、S13I/V94L/M184V/K204T、S13I/T133M/I134L/M184V、S13I/T133M/I134L/K204T、S13I/I134L/K204T、S13I/M184V、S13L、S13T、Q27R、A40W、I46V/P66S/V94L/E112K、I46V/P66S/E112K/T133L/I134L/M184V、I46V/P66S/T133L/I134L、I46V/P66S/T133L/M184V/F197C、I46V/P66S/T133M/F197C、I46V/P66S/I134L/M184V/F197C/K204T、I46V/P66S/M184V、I46V/E112K/T133L/I134L/K204T、I46V/E112M/T133L、I46V/T133M/K204T、I46V/F197C/K204T、M47V/P66L/A71V/L88A/V203I/S235T/S236D、M47V/P66L/A71V/T141S/M184I、M47V/P66L/L88A/M184I/S235T、M47V/P66L/L88A/V203I/S235T/S236D、M47V/P66L/T141S/S235T/S236D、M47V/P66L/M184I/F197M/V203I/S235T/S236D、M47V/P66L/M184I/F197M/S236D、M47V/A71V/L88A/M184I/V203I/S235D、M47V/A71V/L88A/M184I/V203I/S236D、M47V/A71V/T141S/M184I/V203I/S235D、M47V/A71V/M184I、M47V/A71V/M184I/F197M/S236D、M47V/A71V/M184I/S235T、M47V/A71V/M184I/S236D、M47V/L88A/D102E/T141S/S235T/S236D、M47V/L88A/V203I/S235D/S236D、M47V/L88A/S235T/S236D、M47V/D102E/M184I/F197M/S235T/S236D、M47V/D102E/V203I/S235T/S236D、M47V/T141S/M184I、M47V/T141S/M184I/S236D、M47V/M184I/S236D、M47V/V203I/S235D、M47V/V203I/S235T/S236D、M47V/V203I/S236D、M47V/S235T/S236D、E62L、P66A、P66C、P66H、P66L/L88A/D102E/M184I/F197M/V203I/S235T/S236D、P66L/L88A/F197M、P66L/L88A/S235D、P66L/L88A/S235T/S236D、P66L/D102E/M184I/S235D/S236D、P66L/M184I、P66L/F197M/V203I/S235D、P66S/V94L、P66S/V94L/E112K/T133L/M184V、P66S/V94L/E112K/M184V/K204T、P66S/V94L/E112M/T133M/M184V、P66S/E112K/T133L/I134L/F197C、P66S/E112K/I134L/F197C、P66S/E112K/M184V、P66S/E112M/T133L/F197C、P66S/T133L/F197C、P66S/T133M/M184V、P66S/M184V、A84C、A84L、L88A/D102E/T141S/M184I/S235T/S236D、L88A/M184I、L88A/M184I/F197M/V203I/S235T/S236D、L88A/M184I/F197M/S235D/S236D、L88A/M184I/V203I/S235D、L88A/M184I/S236D、L88A/F197M/S235T/S236D、L88A/S236D、L88H、L88V、V94L/E112M/M184V/F197C、V94L/T133L/M184V、Y96L、D102E/T141S/V203I、D102E/M184I/V203I/S236D、D102E/M184I/S236D、D102E/F197M/S235D、E112C、E112K/T133L/M184V/K204T、E112K/T133M/I134L、E112K/I134L/F197C、E112N、N114R、E115D、E115V、E120M、E120R、E127G、E127H、E127L、E127R、E127T、E127V、D132L、T133G、T133H、T133L、T133M/I134L/M184V、T133R、T141S/M184I/V203I/S235T/S236D、T141S/M184I/S235D、T141S/F197M、T141S/V203I/S235D/S236D、T141S/S236D、D146Q、A148G、A148L、M184I/V203I、M184I/V203I/S235D、M184I/V203I/S236D、M184I/S235T/S236D、M184I/S236D、M184V、F197M/S235D、V203I/S235T/S236D、V203I/S236D、K204T、R218S、S235D/S236D、S235T、S235T/S236D、およびS236Dから選択される少なくとも1つの置換または置換セットを含み、ポリペプチド配列のアミノ酸位置は、配列番号6を参照して番号付けされる。
本明細書で使用される場合、以下の用語は、以下の意味を有することが意図される。本発明に関して、本明細書における記載において使用される技術用語および科学用語は、特に他に定義されない限り、当業者によって通常理解される意味を有する。したがって、以下の用語は、以下の意味を有することが意図される。加えて、本明細書において参照される、すべての特許および刊行物は、そのような特許および刊行物に開示されるすべての配列を含んで、参照によって明示的に組み込まれる。
本発明は、デオキシリボースリン酸アルドラーゼ活性を有する操作されたポリペプチド(本明細書において「操作されたデオキシリボースリン酸アルドラーゼポリペプチド」とも称する)を提供する。さらに、本発明は、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、ポリヌクレオチドを含む関連するベクターおよび宿主細胞、操作されたポリペプチドを作製するための方法、および適切な反応条件を含む操作されたポリペプチドを使用するための方法を提供する。
36D、K204T、R218S、S235D/S236D、S235T、S235T/S236DおよびS236Dの置換(複数可)を含み、位置は、配列番号6を参照して番号付けされる。
別の態様では、本発明は、本明細書に記載のデオキシリボースリン酸アルドラーゼ活性を有する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を提供する。ポリヌクレオチドは、遺伝子発現を制御する1つまたは複数の異種調節配列に作動可能に連結させて、ポリペプチドを発現する能力を有する組換えポリヌクレオチドを生じさせ得る。操作されたデオキシリボースリン酸アルドラーゼをコードする異種ポリヌクレオチドを含有する発現構築物を、適切な宿主細胞に導入して、対応する操作されたデオキシリボースリン酸アルドラーゼポリペプチドを発現させることができる。
別の態様では、本明細書に開示される操作されたデオキシリボースリン酸アルドラーゼポリペプチドは、EGAおよびアセトアルデヒドのEDRへの変換のためのプロセスにおいて使用することができる。
本発明のさまざまなフィーチャおよび実施形態を以下の代表的な実施例において説明し、これらは例示的なものであって、限定するものではないことを意図する。
HTP DERA含有湿細胞ペレットの調製
本発明のバリアントを産生するために使用されるDERA(配列番号2)酵素のための親遺伝子を、合成し、pCK110900ベクターにクローニングした(例えば、特許第7,629,157号および米国特許出願公開第2016/0244787号を参照のこと、これらは両方とも、それらの全体がすべての目的のために、参照によって本明細書に組み込まれる)。pCK110900にクローニングする場合、6−ヒスチジンタグを、親のN末端に付加した。W3110 E.coli細胞を、DERAをコードする遺伝子を含有するそれぞれのプラスミドで形質転換し、1%のグルコースおよび30μg/mlのクロラムフェニコール(CAM)を含有するルリアブロス(LB)寒天プレートに蒔き、37℃で終夜成長させた。モノクローナルコロニーを採集し、96ウェルシャローウェルマイクロタイタープレートの1%のグルコースおよび30μg/mLのクロラムフェニコールを含有する180μlのLBに接種した。プレートをO2透過性シールでシールし、培養物を、30℃、200rpmおよび85%湿度で終夜成長させた。次いで、10μlのそれぞれの細胞培養物を、390μlのTBおよび30μg/mLのCAMを含有する96ウェルのディープウェルプレートのウェルに移した。ディープウェルプレートを、O2透過性シールでシールし、0.6〜0.8のOD600に達するまで、30℃、250rpmおよび85%湿度でインキュベートした。次いで、細胞培養物を、イソプロピルチオグリコシド(IPTG)によって1mMの最終濃度に誘導し、30℃、250rpmで18〜20時間終夜インキュベートした。次いで、細胞を、4000rpmで10分間の遠心分離を使用してペレット化した。上清を廃棄し、ペレットを溶解前に−80℃で凍結させた。
DERA含有細胞溶解物の調製
実施例1に記載のようにして調製された凍結DERA含有細胞ペレットを、50mMの3−(N−モルホリノ)プロパンスルホン酸(MOPS)緩衝液、pH7.0、1mg/mLのリゾチームおよび0.5mg/mLのPMBSを含有する400μlの溶解緩衝液を用いて溶解した。溶解混合物を、室温で2時間、振とうした。次いで、プレートを4000rpmおよび4℃で15分間遠心分離した。次いで、上清を、以下の実施例に記載するように、活性レベルを決定するために、清澄にした溶解物として生体触媒反応において使用した。
デオキシリボースリン酸アルドラーゼバリアントによる化合物Y(EDR)の生成
配列番号2を、これらの実験のために、親酵素として選択した。操作された遺伝子のライブラリーを、十分に確立された技法(例えば、飽和変異誘発、および以前に同定された有益な変異の組換え)を使用して、生成した。それぞれの遺伝子によってコードされるポリペプチドを、実施例1に記載されるようにして、HTP中で産生させ、清澄にした溶解物を、実施例2に記載されるようにして、生成した。
デオキシリボースリン酸アルドラーゼバリアントによる化合物Y(EDR)の生成
配列番号6を、これらの実験のために、親酵素として選択した。操作された遺伝子のライブラリーを、十分に確立された技法(例えば、飽和変異誘発、および以前に同定された有益な変異の組換え)を使用して、生成した。それぞれの遺伝子によってコードされるポリペプチドを、実施例1に記載されるようにして、HTP中で産生させ、清澄にした溶解物を、実施例2に記載されるようにして、生成した。
化合物Y(EDR)の分析的検出
実施例3および4に記載のデータは、表5.1における分析方法を使用して収集した。本明細書において提供される方法は、本発明を使用して生成するバリアントの分析において使用される。しかしながら、他の適切な方法が本発明において使用されるので、本明細書に記載の方法は、本明細書に提供されるバリアント、および/または本明細書に提供される方法を使用して生成するバリアントの分析に適用可能な唯一の方法であることは意図しない。
改善されたアルドラーゼ活性についての配列番号466に由来する操作されたポリペプチドの進化およびスクリーニング
配列番号466のデオキシリボースリン酸アルドラーゼ活性を有するポリペプチドをコードする操作されたポリヌクレオチド(配列番号465)を使用して、表6.1の操作されたポリペプチドを生成した。これらのポリペプチドは、出発ポリペプチドと比較して、所望の条件下で(例えば、スキーム1に示されるように、SPおよび操作されたPPMおよびPNP酵素の存在下で化合物1の生成を介して測定された化合物4を生成する能力)、デオキシリボースリン酸アルドラーゼ活性の改善を示した。
Claims (28)
- 配列番号2、6および/もしくは466またはそれらの機能的断片と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高い配列同一性を有するポリペプチド配列を含む操作されたデオキシリボースリン酸アルドラーゼであって、前記操作されたデオキシリボースリン酸アルドラーゼが、前記ポリペプチド配列中に少なくとも1つの置換または置換セットを含み、前記ポリペプチド配列のアミノ酸位置が、配列番号2、6および/または466を参照して番号付けされる、操作されたデオキシリボースリン酸アルドラーゼ。
- 前記ポリペプチド配列が、配列番号2と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高い配列同一性を有し、前記操作されたデオキシリボースリン酸アルドラーゼが、前記ポリペプチド配列中の10/47/66/141/145/156、2、6、9、10/47/88/156、13、31、46、47、47/134/141/212、66、66/88/112/134/141/143/145/212、71、72、88、94、102、104、112、116、133、133/173/204/235/236、134、145、145/173、147、173、184、189、197、203、204、207、226、235、235/236、および236から選択される1つまたは複数の位置に少なくとも1つの置換または置換セットを含み、前記ポリペプチド配列のアミノ酸位置が、配列番号2を参照して番号付けされる、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 前記ポリペプチド配列が、配列番号6と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高い配列同一性を有し、前記操作されたデオキシリボースリン酸アルドラーゼが、前記ポリペプチド配列中の2、2/6/10/66/88/102/184/235/236、2/6/102/141/203/235、2/10/102/235/236、2/47/66/71/141/184/203/235/236、2/47/71/88/203/235/236、2/47/71/141/197/235/236、2/88/141/235/236、2/203/235/236、5、6/203/235/236、9、10/47/66/184/197/236、10/47/66/235/236、10/47/71/184/203/235/236、13、13/46、13/46/66/94、13/46/66/94/184/204、13/46/66/133/134/184、13/46/66/184、13/46/112/134/184、13/46/133/184、13/66/94、13/66/94/184、13/66/112/133/134/184/204、13/66/112/133/134/204、13/66/112/184、13/66/133/134/184/204、13/66/184/204、13/94/133/184、13/94/184、13/94/184/204、13/133/134/184、13/133/134/204、13/134/204、13/184、27、40、46/66/94/112、46/66/112/133/134/184、46/66/133/134、46/66/133/184/197、46/66/133/197、46/66/134/184/197/204、46/66/184、46/112/133、46/112/133/134/204、46/133/204、46/197/204、47/66/71/88/203/235/236、47/66/71/141/184、47/66/88/184/235、47/66/88/203/235/236、47/66/141/235/236、47/66/184/197/203/235/236、47/66/184/197/236、47/71/88/184/203/235、47/71/88/184/203/236、47/71/141/184/203/235、47/71/184、47/71/184/197/236、47/71/184/235、47/71/184/236、47/88/102/141/235/236、47/88/203/235/236、47/88/235/236、47/102/184/197/235/236、47/102/203/235/236、47/141/184、47/141/184/236、47/184/236、47/203/235、47/203/235/236、47/203/236、47/235/236、62、66、66/88/102/184/197/203/235/236、66/88/197、66/88/235、66/88/235/236、66/94、66/94/112/133/184、66/94/112/184/204、66/102/184/235/236、66/112/133/134/197、66/112/133/197、66/112/134/197、66/112/184、66/133/184、66/133/197、66/184、66/197/203/235、84、88、88/102/141/184/235/236、88/184、88/184/197/203/235/236、88/184/197/235/236、88/184/203/235、88/184/236、88/197/235/236、88/236、94/112/184/197、94/133/184、96、102/141/203、102/184/203/236、102/184/236、102/197/235、112、112/133/134、112/133/184/204、112/134/197、114、115、120、127、132、133、133/134/184、141/184/203/235/236、141/184/235、141/197、141/203/235/236、141/236、146、148、184、184/203、184/203/235、184/203/236、184/235/236、184/236、197/235、203/235/236、203/236、204、218、235、235/236、および236から選択される1つまたは複数の位置に少なくとも1つの置換または置換セットを含み、前記ポリペプチド配列のアミノ酸位置が、配列番号6を参照して番号付けされる、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 前記ポリペプチド配列が、配列番号466と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高い配列同一性を有し、前記操作されたデオキシリボースリン酸アルドラーゼが、前記ポリペプチド配列中の71/88/94/133、71/133および133から選択される1つまたは複数の位置に少なくとも1つの置換または置換セットを含み、前記ポリペプチド配列のアミノ酸位置が、配列番号466を参照して番号付けされる、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 表3.1、4.1および/または6.1に示される少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼバリアントの配列と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高く同一であるポリペプチド配列を含む、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 表3.1、4.1および/または6.1に提供されるバリアントの操作されたポリペプチドを含む、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 配列番号2、6および/または466に示される少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼバリアントの配列と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高く同一であるポリペプチド配列を含む、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 配列番号6および/または466に示されるバリアントの操作されたポリペプチドである、請求項6に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 配列番号2〜478の偶数配列に示される少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼバリアントの配列と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高く同一であるポリペプチド配列を含む、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 配列番号2〜478の偶数配列に示されるポリペプチド配列を含む、請求項1に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 野生型Shewanella halifaxensisのデオキシリボースリン酸アルドラーゼと比較して少なくとも1つの改善された性質を示す、請求項1〜10のいずれかに記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 前記改善された性質が、基質に対する改善された活性を含む、請求項11に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 前記基質が、R−2−エチニル−グリセルアルデヒドを含む、請求項12に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 前記改善された性質が、改善された熱安定性を含む、請求項11に記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 精製されている、請求項1〜14のいずれかに記載の操作されたデオキシリボースリン酸アルドラーゼ。
- 請求項1〜15のいずれかに提供される少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼを含む組成物。
- 請求項1〜15のいずれかに記載の少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼをコードするポリヌクレオチド配列。
- 少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼをコードする操作されたポリヌクレオチド配列であって、前記ポリヌクレオチド配列が、配列番号1、5および/または465と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高い配列同一性を含み、前記操作されたデオキシリボースリン酸アルドラーゼの前記ポリヌクレオチド配列が、1つまたは複数の位置に少なくとも1つの置換を含む、操作されたポリヌクレオチド配列。
- 配列番号1、5および/もしくは465またはそれらの機能的断片と少なくとも85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%またはそれよりも高い配列同一性を含む少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼをコードする操作されたポリヌクレオチド配列。
- 配列番号1〜477の奇数配列に示される配列を含む、請求項17〜19のいずれかに記載の操作されたポリヌクレオチド配列。
- 前記ポリヌクレオチド配列が、制御配列に作動可能に連結されている、請求項17〜20のいずれかに記載の操作されたポリヌクレオチド配列。
- コドン最適化されている、請求項17〜21のいずれかに記載の操作されたポリヌクレオチド配列。
- 請求項17〜22のいずれかに記載の少なくとも1つのポリヌクレオチド配列を含む発現ベクター。
- 請求項23に記載の少なくとも1つの発現ベクターを含む宿主細胞。
- 請求項17〜22のいずれかに記載の少なくとも1つのポリヌクレオチド配列を含む宿主細胞。
- 宿主細胞において操作されたデオキシリボースリン酸アルドラーゼを産生させる方法であって、少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼが産生するように、適切な条件下で、培養培地中で請求項24および/または25に記載の宿主細胞を培養することを含む、方法。
- 培養培地および/または宿主細胞から少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼを回収することをさらに含む、請求項26に記載の方法。
- 前記少なくとも1つの操作されたデオキシリボースリン酸アルドラーゼを精製するステップをさらに含む、請求項26および/または27に記載の方法。
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WO2020014041A1 (en) * | 2018-07-09 | 2020-01-16 | Merck Sharp & Dohme Corp. | Enzymatic synthesis of 4'-ethynyl nucleoside analogs |
WO2020154656A1 (en) | 2019-01-25 | 2020-07-30 | Brown University | Compositions and methods for treating, preventing or reversing age-associated inflammation and disorders |
KR20240008455A (ko) * | 2022-07-11 | 2024-01-19 | 대상 주식회사 | L-글루탐산을 생산하는 코리네박테리움 속 변이 미생물 및 이를 이용한 l-글루탐산의 생산 방법 |
Family Cites Families (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1338400C (en) | 1983-08-31 | 1996-06-18 | David H. Gelfand | Recombinant fungal cellulases |
US5308854A (en) | 1990-06-18 | 1994-05-03 | Merck & Co., Inc. | Inhibitors of HIV reverse transcriptase |
US5527819A (en) | 1991-09-06 | 1996-06-18 | Merck & Co., Inc. | Inhibitors of HIV reverse transcriptase |
US6309883B1 (en) | 1994-02-17 | 2001-10-30 | 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 |
US6335160B1 (en) | 1995-02-17 | 2002-01-01 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
US6995017B1 (en) | 1994-02-17 | 2006-02-07 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US6165793A (en) | 1996-03-25 | 2000-12-26 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US6406855B1 (en) | 1994-02-17 | 2002-06-18 | Maxygen, Inc. | Methods and compositions for polypeptide engineering |
US6395547B1 (en) | 1994-02-17 | 2002-05-28 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US5837458A (en) | 1994-02-17 | 1998-11-17 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
US5834252A (en) | 1995-04-18 | 1998-11-10 | Glaxo Group Limited | End-complementary polymerase reaction |
US5928905A (en) | 1995-04-18 | 1999-07-27 | Glaxo Group Limited | End-complementary polymerase reaction |
US5605793A (en) | 1994-02-17 | 1997-02-25 | Affymax Technologies N.V. | Methods for in vitro recombination |
US20060257890A1 (en) | 1996-05-20 | 2006-11-16 | Maxygen, Inc. | Methods and compositions for cellular and metabolic engineering |
JP3649338B2 (ja) | 1994-06-03 | 2005-05-18 | ノボザイムス バイオテック,インコーポレイティド | 精製されたマイセリオフトラ・ラッカーゼ及びそれをコードする核酸 |
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 |
US6506602B1 (en) | 1996-03-25 | 2003-01-14 | Maxygen, Inc. | Methods for generating polynucleotides having desired characteristics by iterative selection and recombination |
US6096548A (en) | 1996-03-25 | 2000-08-01 | Maxygen, Inc. | Method for directing evolution of a virus |
IL130635A0 (en) | 1997-01-17 | 2000-06-01 | Maxygen Inc | Evolution of whole cells and organisms by recursive sequence recombination |
US6326204B1 (en) | 1997-01-17 | 2001-12-04 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
WO1998031816A1 (en) | 1997-01-17 | 1998-07-23 | Regents Of The University Of Minnesota | Dna molecules and protein displaying improved triazine compound degrading ability |
US7148054B2 (en) | 1997-01-17 | 2006-12-12 | Maxygen, Inc. | Evolution of whole cells and organisms by recursive sequence recombination |
DK2270234T3 (da) | 1997-12-08 | 2013-06-03 | California Inst Of Techn | Fremgangsmåde til fremstilling af polynukleotid- og polypeptidsekvenser |
JP2002510506A (ja) | 1998-04-02 | 2002-04-09 | テラス ジェネティック リソーシズ,インコーポレイティド | 遺伝子配列に遺伝障害を有する植物を得る方法 |
CN1314911A (zh) | 1998-05-01 | 2001-09-26 | 麦克西根股份有限公司 | 用dna改组优化害虫抗性基因 |
KR20010052894A (ko) | 1998-06-17 | 2001-06-25 | 맥시겐, 인크. | 목적하는 특성을 보유한 폴리뉴클레오티드를 생성하는 방법 |
US6365408B1 (en) | 1998-06-19 | 2002-04-02 | Maxygen, Inc. | Methods of evolving a polynucleotides by mutagenesis and recombination |
US6605430B1 (en) | 1998-08-12 | 2003-08-12 | Maxygen, Inc. | DNA shuffling of monooxygenase genes for production of industrial chemicals |
CA2345356C (en) | 1998-10-06 | 2012-10-02 | Mark Aaron Emalfarb | Transformation system in the field of filamentous fungal hosts |
EP1119616A2 (en) | 1998-10-07 | 2001-08-01 | Maxygen, Inc. | Dna shuffling to produce nucleic acids for mycotoxin detoxification |
WO2000028018A1 (en) | 1998-11-10 | 2000-05-18 | Maxygen, Inc. | Modified adp-glucose pyrophosphorylase for improvement and optimization of plant phenotypes |
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 |
US6376246B1 (en) | 1999-02-05 | 2002-04-23 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
US6917882B2 (en) | 1999-01-19 | 2005-07-12 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
US6368861B1 (en) | 1999-01-19 | 2002-04-09 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
US6436675B1 (en) | 1999-09-28 | 2002-08-20 | Maxygen, Inc. | Use of codon-varied oligonucleotide synthesis for synthetic shuffling |
US20070065838A1 (en) | 1999-01-19 | 2007-03-22 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
US7873477B1 (en) | 2001-08-21 | 2011-01-18 | Codexis Mayflower Holdings, Llc | Method and system using systematically varied data libraries |
US7702464B1 (en) | 2001-08-21 | 2010-04-20 | Maxygen, Inc. | Method and apparatus for codon determining |
US7024312B1 (en) | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
US8457903B1 (en) | 1999-01-19 | 2013-06-04 | Codexis Mayflower Holdings, Llc | Method and/or apparatus for determining codons |
EP2253704B1 (en) | 1999-01-19 | 2015-08-19 | Codexis Mayflower Holdings, LLC | Oligonucleotide mediated nucleic acid recombination |
US6961664B2 (en) | 1999-01-19 | 2005-11-01 | Maxygen | Methods of populating data structures for use in evolutionary simulations |
IL144657A0 (en) | 1999-02-11 | 2002-06-30 | Maxygen Inc | High throughput mass spectrometry |
CA2364997A1 (en) | 1999-03-05 | 2000-09-08 | Maxygen, Inc. | Encryption of traits using split gene sequences |
US6703240B1 (en) | 1999-04-13 | 2004-03-09 | Maxygar, Inc. | Modified starch metabolism enzymes and encoding genes for improvement and optimization of plant phenotypes |
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 |
US6686515B1 (en) | 1999-11-23 | 2004-02-03 | Maxygen, Inc. | Homologous recombination in plants |
JP2003519495A (ja) | 2000-01-11 | 2003-06-24 | マキシジェン, インコーポレイテッド | 多様性生成およびスクリーニングのための一体化されたシステムおよび方法 |
EP1272967A2 (en) | 2000-03-30 | 2003-01-08 | Maxygen, Inc. | In silico cross-over site selection |
JP2004508011A (ja) | 2000-04-03 | 2004-03-18 | マキシジェン, インコーポレイテッド | スブチリシン変異体 |
JP4058665B2 (ja) | 2001-03-02 | 2008-03-12 | 有機合成薬品工業株式会社 | 2−デオキシリボース5−リン酸の製造方法 |
WO2003075129A2 (en) | 2002-03-01 | 2003-09-12 | Maxygen, Inc. | Methods, systems, and software for identifying functional bio-molecules |
US20050084907A1 (en) | 2002-03-01 | 2005-04-21 | Maxygen, Inc. | Methods, systems, and software for identifying functional biomolecules |
US7747391B2 (en) | 2002-03-01 | 2010-06-29 | Maxygen, Inc. | Methods, systems, and software for identifying functional biomolecules |
WO2003078583A2 (en) | 2002-03-09 | 2003-09-25 | Maxygen, Inc. | Optimization of crossover points for directed evolution |
AU2003263031A1 (en) * | 2002-09-20 | 2004-04-08 | Diversa Corporation | Chemoenzymatic methods for the synthesis of statins and stain intermediates |
WO2005017135A1 (en) | 2003-08-11 | 2005-02-24 | Codexis, Inc. | Improved ketoreductase polypeptides and related polynucleotides |
CA2568728A1 (en) * | 2004-06-04 | 2005-12-15 | Dsm Ip Assets B.V. | Improved 2-deoxy-d-ribose 5-phosphate aldolases (deras) and the uses thereof |
WO2007132461A2 (en) * | 2006-05-11 | 2007-11-22 | Ramot At Tel Aviv University Ltd. | Classification of protein sequences and uses of classified proteins |
WO2008143679A2 (en) | 2006-06-01 | 2008-11-27 | Verenium Corporation | Nucleic acids and proteins and methods for making and using them |
US20090118130A1 (en) | 2007-02-12 | 2009-05-07 | Codexis, Inc. | Structure-activity relationships |
WO2009102901A1 (en) | 2008-02-12 | 2009-08-20 | Codexis, Inc. | Method of generating an optimized, diverse population of variants |
US8504498B2 (en) | 2008-02-12 | 2013-08-06 | Codexis, Inc. | Method of generating an optimized, diverse population of variants |
US8383346B2 (en) | 2008-06-13 | 2013-02-26 | Codexis, Inc. | Combined automated parallel synthesis of polynucleotide variants |
US20090312196A1 (en) | 2008-06-13 | 2009-12-17 | Codexis, Inc. | Method of synthesizing polynucleotide variants |
HUE041367T2 (hu) | 2008-06-13 | 2019-05-28 | Codexis Inc | Eljárás polinukleotid-változatok szintézisére |
EP2723763A4 (en) | 2011-06-24 | 2015-02-18 | Merck Sharp & Dohme | IMMOBILIZED TRANSAMINASES AND METHODS OF MAKING AND USING THE SAME |
DK2726651T3 (en) | 2011-06-28 | 2019-01-28 | Codexis Inc | PROTEIN INVARIANT GENERATION BY REGION SHUFFLING |
US20150133698A1 (en) | 2012-04-20 | 2015-05-14 | Codexis, Inc. | Production of fatty alcohols from engineered microorganisms |
US10415067B2 (en) | 2014-05-26 | 2019-09-17 | Scientist of Fortune, S.A. | Method for the enzymatic production of D-erythrose and acetyl phosphate |
SG11202012107RA (en) | 2018-07-09 | 2021-01-28 | Codexis Inc | Engineered deoxyribose-phosphate aldolases |
-
2019
- 2019-07-02 SG SG11202012107RA patent/SG11202012107RA/en unknown
- 2019-07-02 WO PCT/US2019/040369 patent/WO2020014048A1/en active Application Filing
- 2019-07-02 EP EP19833390.8A patent/EP3821015A4/en active Pending
- 2019-07-02 CA CA3103721A patent/CA3103721A1/en active Pending
- 2019-07-02 KR KR1020217003782A patent/KR20210032417A/ko unknown
- 2019-07-02 CN CN201980057974.4A patent/CN112673105A/zh active Pending
- 2019-07-02 MX MX2021000326A patent/MX2021000326A/es unknown
- 2019-07-02 US US16/460,118 patent/US11274286B2/en active Active
- 2019-07-02 JP JP2021500435A patent/JP7462969B2/ja active Active
- 2019-07-02 AU AU2019300836A patent/AU2019300836A1/en active Pending
-
2020
- 2020-12-30 IL IL279882A patent/IL279882A/en unknown
-
2022
- 2022-02-04 US US17/592,869 patent/US11845968B2/en active Active
-
2023
- 2023-11-07 US US18/503,542 patent/US20240076647A1/en active Pending
Non-Patent Citations (2)
Title |
---|
DICK, MARKUS ET AL.: ""Trading off stability against activity in extremophilic aldolases"", SCIENTIFIC REPORTS, vol. 6, no. 1, JPN6023021152, 19 January 2016 (2016-01-19), ISSN: 0005151809 * |
JENNEWEIN, STEFAN ET AL.: ""Directed evolution of an industrial biocatalyst: 2-deoxy-D-ribose 5-phosphate aldolase"", BIOTECHNOLOGY JOURNAL, vol. 1, no. 5, JPN6023021151, May 2006 (2006-05-01), pages 537 - 548, ISSN: 0005151808 * |
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