对映体药物
还原胺化
拉萨吉林
组合化学
化学
立体选择性
对映体过量
动力学分辨率
酮
对映体
定向进化
有机化学
对映选择合成
催化作用
突变体
生物化学
医学
基因
病理
疾病
帕金森病
作者
Kai Zhang,Yuanzhi He,Jin Zhu,Qi Zhang,Luyao Tang,Li Cui,Yue Feng
标识
DOI:10.3389/fbioe.2021.798147
摘要
Reductive aminases (RedAms) for the stereoselective amination of ketones represent an environmentally benign and economically viable alternative to transition metal-catalyzed asymmetric chemical synthesis. Here, we report two RedAms from Aspergillus calidoustus (AcRedAm) and bacteria (BaRedAm) with NADPH-dependent features. The enzymes can synthesize a set of secondary amines using a broad range of ketone and amine substrates with up to 97% conversion. To synthesize the pharmaceutical ingredient (R)-rasagiline, we engineered AcRedAm through rational design to obtain highly stereoselective mutants. The best mutant Q237A from AcRedAm could synthesize (R)-rasagiline with >99% enantiomeric excess with moderate conversion. The features of AcRedAm and BaRedAm highlight their potential for further study and expand the biocatalytic toolbox for industrial applications.
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