生物催化
还原胺化
胺气处理
组合化学
亚胺
胺化
化学
非对映体
结合
烯烃
手性(物理)
对映选择合成
有机化学
催化作用
反应机理
物理
数学分析
夸克
量子力学
手征对称破缺
数学
Nambu–Jona Lasinio模型
作者
Thomas W. Thorpe,Judi Marshall,Vanessa Harawa,Rebecca E. Ruscoe,Aníbal Cuetos,James Finnigan,Antonio Angelastro,Rachel S. Heath,Fabio Parmeggiani,Simon J. Charnock,Roger M. Howard,Rajesh Kumar,David S. B. Daniels,Gideon Grogan,Nicholas J. Turner
出处
期刊:Nature
[Springer Nature]
日期:2022-04-06
卷期号:604 (7904): 86-91
被引量:48
标识
DOI:10.1038/s41586-022-04458-x
摘要
Chiral amine diastereomers are ubiquitous in pharmaceuticals and agrochemicals1, yet their preparation often relies on low-efficiency multi-step synthesis2. These valuable compounds must be manufactured asymmetrically, as their biochemical properties can differ based on the chirality of the molecule. Herein we characterize a multifunctional biocatalyst for amine synthesis, which operates using a mechanism that is, to our knowledge, previously unreported. This enzyme (EneIRED), identified within a metagenomic imine reductase (IRED) collection3 and originating from an unclassified Pseudomonas species, possesses an unusual active site architecture that facilitates amine-activated conjugate alkene reduction followed by reductive amination. This enzyme can couple a broad selection of α,β-unsaturated carbonyls with amines for the efficient preparation of chiral amine diastereomers bearing up to three stereocentres. Mechanistic and structural studies have been carried out to delineate the order of individual steps catalysed by EneIRED, which have led to a proposal for the overall catalytic cycle. This work shows that the IRED family can serve as a platform for facilitating the discovery of further enzymatic activities for application in synthetic biology and organic synthesis.
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