Actinomycetes-derived imine reductases with a preference towards bulky amine substrates

文献类型： 外文期刊

第一作者： Zhang, Jun

作者： Zhang, Jun;Ma, Yaqing;Wu, Qiaqing;Sun, Zhoutong;Gao, Shu-Shan;Cui, Chengsen;Zhang, Jun;Li, Xin;Wang, Bin-Gui;Chen, Rongchang;Tan, Xianwei;Liu, Xiongduo;Ma, Yaqing;Zhu, Fangfang;An, Chunyan;Wei, Guangzheng;Yao, Yongpeng;Yang, Lujia;Wu, Qiaqing;Sun, Zhoutong;Gao, Shu-Shan;Cui, Chengsen;Zhang, Peng

作者机构：

期刊名称：COMMUNICATIONS CHEMISTRY （ 影响因子：7.211； 五年影响因子：7.243 ）

ISSN： 2399-3669

年卷期： 2022 年 5 卷 1 期

页码：

收录情况： SCI

摘要： Since imine reductases (IREDs) were reported to catalyze the reductive amination reactions, they became particularly attractive for producing chiral amines. Though diverse ketones and aldehydes have been proved to be excellent substrates of IREDs, bulky amines have been rarely transformed. Here we report the usage of an Increasing-Molecule-Volume-Screening to identify a group of IREDs (IR-G02, 21, and 35) competent for accepting bulky amine substrates. IR-G02 shows an excellent substrate scope, which is applied to synthesize over 135 amine molecules as well as a range of APIs' substructures. The crystal structure of IR-G02 reveals the determinants for altering the substrate preference. Finally, we demonstrate a gram-scale synthesis of an analogue of the API sensipar via a kinetic resolution approach, which displays ee >99%, total turnover numbers of up to 2087, and space time yield up to 18.10 g L-1 d(-1). Imine reductases can catalyze reductive amination reactions to produce chiral amines, however, transformation of bulky amines has been challenging. Here, by using an increasing-molecule-volume-screening method, the authors identify a group of imine reductases that can accept bulky amines and achieve an efficient gram-scale synthesis of an API sensipar analogue.

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