对称化
环氧化物水解酶
动力学分辨率
环氧化物
基质(水族馆)
立体选择性
邻接
化学
生物催化
立体化学
对映选择合成
组合化学
水解酶
水解
定向进化
产量(工程)
催化作用
酶
有机化学
生物化学
反应机理
材料科学
生物
冶金
生态学
微粒体
基因
突变体
作者
Kaori Hiraga,Tetsuji Itoh,Deeptak Verma,Wei Wang,Chen Huang,Michael J. Ardolino,Yong‐Li Zhong,Grant S. Murphy
出处
期刊:Chemcatchem
[Wiley]
日期:2023-05-15
卷期号:15 (12)
被引量:1
标识
DOI:10.1002/cctc.202300238
摘要
Abstract Chiral vicinal diols are important intermediates in the synthesis of pharmaceuticals. Epoxide hydrolases catalyze hydrolytic ring opening of epoxides to produce the corresponding vicinal diols, providing an attractive way to access these building blocks under mild conditions in a stereoselective and atom‐efficient manner. In this study, an epoxide hydrolase is identified and engineered to form ( 3S,4S )‐tetrahydrofurandiol in high optical purity via the desymmetrization of meso ‐3,4‐epoxytetrahydrofuran. In nine rounds of directed evolution, the enzyme's native ( 3R,4R )‐stereopreference was reversed and its activity was dramatically improved to achieve quantitative yield under remarkably high 500 g/L substrate concentration and low enzyme loading. Computational modelling provides insights on the changes in enzyme‐substrate interaction that result in divergent enantioselectivities afforded by evolved variants.
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