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通过对一系列宏基因组的亚胺还原酶进行筛选和表征实现生物催化还原胺化
作者:小柯机器人 发布时间:2021/1/3 15:32:48

英国曼彻斯特大学的Nicholas J. Turner研究团队通过对一系列不同的亚胺还原酶进行筛选和表征,成功实现了还原胺化反应的生物催化。相关论文发表在2020年12月30日出版的《自然-化学》杂志上。

在该文中,研究者报道了超过300种新发现的亚胺还原酶,并产生了一个大(384种酶)且序列多样的用于筛选的亚胺还原酶库。研究人员还开发了一个简便高通量的筛选其活性的方法。通过这一途径,研究人员发现了可接受不同结构酮和胺的亚胺还原酶生物催化剂,包括通过动态动力学拆分实现N-取代的β-氨基酯衍生物的制备级合成,且产率和手性选择性优越。

据了解,寻找一个快速简便的方法筛选蛋白质序列空间以发现用于非对称合成的新型生物催化剂仍是酶发现过程中的挑战和限速步。用于合成手性胺的生物催化策略愈发诱人,这其中包括酶催化不对称还原胺化反应,它可以为许多高附加值产物提供一条高效合成路线。

附:英文原文

Title: Screening and characterization of a diverse panel of metagenomic imine reductases for biocatalytic reductive amination

Author: James R. Marshall, Peiyuan Yao, Sarah L. Montgomery, James D. Finnigan, Thomas W. Thorpe, Ryan B. Palmer, Juan Mangas-Sanchez, Richard A. M. Duncan, Rachel S. Heath, Kirsty M. Graham, Darren J. Cook, Simon J. Charnock, Nicholas J. Turner

Issue&Volume: 2020-12-30

Abstract: Finding faster and simpler ways to screen protein sequence space to enable the identification of new biocatalysts for asymmetric synthesis remains both a challenge and a rate-limiting step in enzyme discovery. Biocatalytic strategies for the synthesis of chiral amines are increasingly attractive and include enzymatic asymmetric reductive amination, which offers an efficient route to many of these high-value compounds. Here we report the discovery of over 300 new imine reductases and the production of a large (384 enzymes) and sequence-diverse panel of imine reductases available for screening. We also report the development of a facile high-throughput screen to interrogate their activity. Through this approach we identified imine reductase biocatalysts capable of accepting structurally demanding ketones and amines, which include the preparative synthesis of N-substituted β-amino ester derivatives via a dynamic kinetic resolution process, with excellent yields and stereochemical purities.

DOI: 10.1038/s41557-020-00606-w

Source: https://www.nature.com/articles/s41557-020-00606-w

期刊信息

Nature Chemistry:《自然—化学》,创刊于2009年。隶属于施普林格·自然出版集团,最新IF:21.687
官方网址:https://www.nature.com/nchem/
投稿链接:https://mts-nchem.nature.com/cgi-bin/main.plex