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

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 r...

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Published in:Communications chemistry 2022-10, Vol.5 (1), p.123-123, Article 123
Main Authors: Zhang, Jun, Li, Xin, Chen, Rongchang, Tan, Xianwei, Liu, Xiongduo, Ma, Yaqing, Zhu, Fangfang, An, Chunyan, Wei, Guangzheng, Yao, Yongpeng, Yang, Lujia, Zhang, Peng, Wu, Qiaqing, Sun, Zhoutong, Wang, Bin-Gui, Gao, Shu-Shan, Cui, Chengsen
Format: Article
Language:English
Subjects:
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631/92/607
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82/83
Actinomycetes
Aldehydes
Amines
Biocatalysts
Chemical reactions
Chemical synthesis
Chemistry
Chemistry and Materials Science
Chemistry/Food Science
Conversion
Crystal structure
Enzymes
Ketones
Laboratories
Reductases
Screening
Substrates
Substructures (crystalline)
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Summary: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.
ISSN:2399-3669
2399-3669
DOI:10.1038/s42004-022-00743-y