氧化脱氨基
对映体药物
脱氨基
氨基酸
化学
动力学分辨率
饱和突变
蛋白质工程
定向进化
DNA洗牌
生物催化
突变
基质(水族馆)
胺气处理
立体化学
组合化学
酶
生物化学
有机化学
对映选择合成
催化作用
反应机理
生物
突变体
生态学
基因
作者
Xinjian Yin,Wenzhong Gong,Yuping Zeng,Hulin Qiu,Lan Liu,Frank Hollmann,Bi‐Shuang Chen
标识
DOI:10.1021/acscatal.3c04995
摘要
The biocatalytic oxidative deamination of β-amino alcohols holds significant practical potential in kinetic resolution and/or deracemization process to access (R)-β-amino alcohols. This study exemplifies a notable instance of acquisition and utilization of this valuable oxidative deamination activity. Initially, the mutation N261M (M0) was identified to endow a native valine dehydrogenase with oxidative deamination activity toward a few (S)-β-amino alcohols. Subsequently, a phylogenetic analysis-guided, double-code saturation mutagenesis strategy was proposed to engineer M0's side-chain binding site. This strategy facilitated the substrate-specific evolution of M0, resulting in the creation of a panel of mutants (M1–M4) with noteworthy oxidative deamination activity toward structurally diverse (S)-β-amino alcohols. Using these engineered amine dehydrogenases, termed as β-amino alcohol dehydrogenases (β-AADHs), the complete kinetic resolution and even deracemization of a range of β-amino alcohols have been achieved. This work reports distinct biocatalysts and a synthetic strategy for the synthesis of enantiopure (R)-β-amino alcohols and offers an innovative approach for substrate-specificity engineering of enzymes.
科研通智能强力驱动
Strongly Powered by AbleSci AI