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
收藏
页码：11905 / 11912
页数：8
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