Directed evolution of a carbonyl reductase LsCR for the enantioselective synthesis of (1S)-2-chloro-1-(3,4-difluorophenyl) ethanol.

2-Propanol Alcohol Oxidoreductases / genetics Catalysis Ethanol Stereoisomerism
Carbonyl reductase Catalytic performance Computer-aided design Protein engineering

Journal

Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703

Informations de publication

Date de publication:
10 2022
Historique:
received: 09 05 2022
revised: 22 06 2022
accepted: 23 06 2022
pubmed: 12 7 2022
medline: 16 8 2022
entrez: 11 7 2022
Statut: ppublish

Résumé

Traditional screening methods of enzyme engineering often require building large mutant libraries to screen for potentially beneficial sites, which are often time-consuming and labor-intensive with low mining efficiency. In this study, a novel enzyme engineering strategy was established to modify carbonyl reductase LsCR for the synthesis of (1S)-2-chloro-1-(3,4-difluorophenyl) ethanol ((S)-CFPL), which is a key intermediate of anticoagulant drug ticagrelor. The strategy was developed by combining HotSpot, FireProt and multiple sequence alignment, resulting in the construction of a "small and smart" mutant library including 10 mutations. Among them, 5 mutations were positive, resulting in a 50% mining accuracy of beneficial sites. Finally, a highly active mutant LsCR

Identifiants

DOI: 10.1016/j.bioorg.2022.105991 PMID: 35816872
pubmed: 35816872
pii: S0045-2068(22)00397-2
doi: 10.1016/j.bioorg.2022.105991
pii:
doi:

Substances chimiques

Ethanol 3K9958V90M
Alcohol Oxidoreductases EC 1.1.-
2-Propanol ND2M416302

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

105991

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Auteurs

Hua-Tao Liu (HT)

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China; Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Chun-Yue Weng (CY)

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China; Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Shen-Yuan Xu (SY)

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China; Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Shu-Fang Li (SF)

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China; Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

Ya-Jun Wang (YJ)

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China; Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P. R. China. Electronic address: wangyj@zjut.edu.cn.

Yu-Guo Zheng (YG)

Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, P. R. China; Engineering Research Center of Bioconversion and Biopurification of the Ministry of Education, Zhejiang University of Technology, Hangzhou, Zhejiang 310014, P. R. China; The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

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Classifications MeSH

questionsmedicales.fr › Composés chimiques organiques › Alcools › Propanols › Propan-2-ol › Directed evolution of a carbonyl reductase...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Alcohol oxidoreductases › Directed evolution of a carbonyl reductase...
questionsmedicales.fr › Phénomènes chimiques › Catalyse › Directed evolution of a carbonyl reductase...
questionsmedicales.fr › Composés chimiques organiques › Alcools › Éthanol › Directed evolution of a carbonyl reductase...
questionsmedicales.fr › Phénomènes chimiques › Phénomènes de chimie organique › Isomérie › Stéréoisomérie › Directed evolution of a carbonyl reductase...