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

• DOI: 10.1038/s42004-022-00743-y
• Publication Date: 2022-10-08T12:02:29Z
• Authors: Jun Zhang; Xin Li; Rongchang Chen; Xianwei Tan; Xiongduo Liu; Yaqing Ma; Fangfang Zhu; Chunyan An; Guangzheng Wei; Yongpeng Yao; Lujia Yang; Peng Zhang; Qiaqing Wu; Zhoutong Sun; Bin-Gui Wang; Shu-Shan Gao; Chengsen Cui
• Keywords: Chemistry; QD1-999; 01 natural sciences; Article; 0104 chemical sciences

AbstractSince 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.