WO2015168999A8 - 双羰基还原酶突变体及其应用 - Google Patents

双羰基还原酶突变体及其应用 Download PDF

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Publication number
WO2015168999A8
WO2015168999A8 PCT/CN2014/083648 CN2014083648W WO2015168999A8 WO 2015168999 A8 WO2015168999 A8 WO 2015168999A8 CN 2014083648 W CN2014083648 W CN 2014083648W WO 2015168999 A8 WO2015168999 A8 WO 2015168999A8
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WIPO (PCT)
Prior art keywords
double
same
carbonyl reductase
mutant
reductase mutant
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PCT/CN2014/083648
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English (en)
French (fr)
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WO2015168999A1 (zh
Inventor
洪浩
盖吉詹姆斯
高峰
刘立辉
于文燕
刘芳
郭莉娜
张娜
Original Assignee
凯莱英医药集团（天津）股份有限公司
凯莱英生命科学技术(天津)有限公司
天津凯莱英制药有限公司
凯莱英医药化学（阜新）技术有限公司
吉林凯莱英医药化学有限公司
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Application filed by 凯莱英医药集团（天津）股份有限公司, 凯莱英生命科学技术(天津)有限公司, 天津凯莱英制药有限公司, 凯莱英医药化学（阜新）技术有限公司, 吉林凯莱英医药化学有限公司 filed Critical 凯莱英医药集团（天津）股份有限公司
Priority to JP2016567554A priority Critical patent/JP6473175B2/ja
Priority to ES14891354T priority patent/ES2733948T3/es
Priority to US15/309,690 priority patent/US10131883B2/en
Priority to KR1020167034582A priority patent/KR102176054B1/ko
Priority to EP14891354.4A priority patent/EP3141601B1/en
Publication of WO2015168999A1 publication Critical patent/WO2015168999A1/zh
Publication of WO2015168999A8 publication Critical patent/WO2015168999A8/zh

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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
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
    • 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
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • 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
    • C12P7/00—Preparation of oxygen-containing organic compounds
    • C12P7/62—Carboxylic acid esters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01184—Carbonyl reductase (NADPH) (1.1.1.184)

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biomedical Technology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Cell Biology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

提供了双羰基还原酶突变体，其核苷酸编码序列及包含所述序列的表达盒、重组载体和宿主细胞，及所述突变体用于制备3R，5S-双羰基化合物的方法，所获得的3R，5S-双羰基化合物的ee值大于99％，de值约90％。所述双羰基还原酶突变体为关键的药物中间体，尤其是他汀类药物的手性二羰基己酸链的合成提供了高效的催化剂。
PCT/CN2014/083648 2014-05-09 2014-08-04 双羰基还原酶突变体及其应用 WO2015168999A1 (zh)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2016567554A JP6473175B2 (ja) 2014-05-09 2014-08-04 ジカルボニル還元酵素突然変異体及びその応用
ES14891354T ES2733948T3 (es) 2014-05-09 2014-08-04 Doble carbonilo reductasa mutante y aplicación de la misma
US15/309,690 US10131883B2 (en) 2014-05-09 2014-08-04 Diketoreductase mutant and application thereof
KR1020167034582A KR102176054B1 (ko) 2014-05-09 2014-08-04 Diketoreductase 돌연변이체 및 그 응용
EP14891354.4A EP3141601B1 (en) 2014-05-09 2014-08-04 Double-carbonyl reductase mutant and application of same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201410196920.5A CN103966176B (zh) 2014-05-09 2014-05-09 双羰基还原酶突变体及其应用
CN201410196920.5 2014-05-09

Publications (2)

Publication Number Publication Date
WO2015168999A1 WO2015168999A1 (zh) 2015-11-12
WO2015168999A8 true WO2015168999A8 (zh) 2018-12-06

Family

ID=51236183

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2014/083648 WO2015168999A1 (zh) 2014-05-09 2014-08-04 双羰基还原酶突变体及其应用

Country Status (7)

Country Link
US (1) US10131883B2 (zh)
EP (1) EP3141601B1 (zh)
JP (1) JP6473175B2 (zh)
KR (1) KR102176054B1 (zh)
CN (2) CN103966176B (zh)
ES (1) ES2733948T3 (zh)
WO (1) WO2015168999A1 (zh)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103966176B (zh) 2014-05-09 2017-12-22 凯莱英医药集团（天津）股份有限公司 双羰基还原酶突变体及其应用
WO2016095223A1 (zh) * 2014-12-19 2016-06-23 凯莱英医药集团（天津）股份有限公司 双羰基还原酶突变体及其应用
CN104560907B (zh) * 2014-12-19 2017-12-22 凯莱英医药集团（天津）股份有限公司 双羰基还原酶突变体及其应用
CN108048416B (zh) * 2017-12-25 2021-05-18 吉林凯莱英医药化学有限公司 改进的酮还原酶突变体及其制备方法和应用
CN110387359B (zh) * 2018-04-17 2021-04-20 湖州颐盛生物科技有限公司 羰基还原酶突变体及其应用
JPWO2021100848A1 (zh) * 2019-11-22 2021-05-27
CN113801859B (zh) * 2021-09-29 2023-08-01 山东睿鹰制药集团有限公司 一种用于制备手性醇化合物的羰基还原酶突变体及其用途

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101429514B (zh) * 2007-11-08 2011-06-15 陈依军 一种双羰基还原酶、其基因及其应用
CN101880694B (zh) * 2009-12-01 2014-06-11 陈依军 一种非水相制备手性3r,5s-双羟基化合物的方法
CN102277338A (zh) * 2011-08-02 2011-12-14 中国药科大学 双羰基还原酶突变体及其应用
CN102517241B (zh) * 2011-12-19 2013-06-19 中国药科大学 一种含有d型氨基酸的双羰基还原酶的突变体的制备方法
CN103937761B (zh) * 2014-05-06 2017-03-22 凯莱英医药集团（天津）股份有限公司 双羰基还原酶、其编码基因及应用
CN103937759B (zh) * 2014-05-06 2017-03-22 凯莱英医药集团（天津）股份有限公司 双羰基还原酶、其编码基因及应用
CN103966176B (zh) 2014-05-09 2017-12-22 凯莱英医药集团（天津）股份有限公司 双羰基还原酶突变体及其应用

Also Published As

Publication number Publication date
KR20170002619A (ko) 2017-01-06
CN107603961B (zh) 2020-04-24
JP6473175B2 (ja) 2019-02-20
WO2015168999A1 (zh) 2015-11-12
ES2733948T3 (es) 2019-12-03
US20170152488A1 (en) 2017-06-01
CN103966176B (zh) 2017-12-22
JP2017518744A (ja) 2017-07-13
CN103966176A (zh) 2014-08-06
EP3141601B1 (en) 2019-06-12
KR102176054B1 (ko) 2020-11-09
EP3141601A4 (en) 2017-09-20
US10131883B2 (en) 2018-11-20
EP3141601A1 (en) 2017-03-15
CN107603961A (zh) 2018-01-19

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