Semirational Engineering of a Thermostable Carbonyl Reductase for the Precision Synthesis of (2R,3R)-2-Methyl-2-benzyl-3-hydroxycyclopentanone and Its Analogues

被引：2

作者：

Zhu, Liangyan ^{[1
,2
,3
]}

Chen, Xi ^{[1
,2
,3
]}

Feng, Jinhui ^{[1
,2
,3
]}

Cui, Yunfeng ^{[1
,2
]}

Wu, Qiaqing ^{[1
,2
,3
]}

Zhu, Dunming ^{[1
,2
,3
]}

机构：

[1] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Ctr Technol Innovat Synthet Biol, Natl Engn Res Ctr Ind Enzymes, Tianjin 300308, Peoples R China

[2] Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin Engn Res Ctr Biocatalyt Technol, Tianjin 300308, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2023年 / 88卷 / 16期

基金：

中国国家自然科学基金;

关键词：

DESYMMETRIZATION;

D O I：

10.1021/acs.joc.3c01192

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

2,2-Disubstituted-3-hydroxycyclopentanonesare important chiralintermediates for natural products and pharmaceuticals. Through semirationalengineering of a thermostable carbonyl reductase CBCR from Cupriavidus sp. BIS7, a mutant L91C/F93I was obtained.Mutant L91C/F93I showed 4- to 36-fold enhanced activities toward 2-methyl-2-benzyl-1,3-cyclopentanedioneand its analogues, affording the (2R,3R)-stereoisomers with >99% ee and >99% de. Enzyme-substratedocking studies were performed to reveal the molecular basis for theactivity and stereoselectivity improvements.

引用

页码：11905 / 11912

页数：8

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