将蛋白质工程学应用于烯还原酶,通过不对称反应合成手性化合物。

IF 8.1 2区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jiacheng Feng, Huiru Ye, Changxin Lu, Linyan Pan, Hanchi Chen, Linjiang Zhu, Xiaolong Chen
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引用次数: 0

摘要

炔还原酶(ER)具有底物杂合性、光激发反应性和同时产生两个手性中心的优良特性,因此被广泛应用于手性中间体的不对称合成。天然 ER 通常具有相同的立体选择性,因此需要对它们进行改造,以获得相反构型的手性化合物。ER 对活化烯的氢化过程由还原半反应和氧化半反应组成,这两个反应依赖于两种辅助因子 NAD(P)H 和黄素单核苷酸。底物的大小、抽电子基团的活化强度、辅助因子的氧化还原电位以及催化腔周围环路的灵活性都会影响ER的催化活性。目前,ER 蛋白工程已被成功用于增强各种催化特性,包括光激发不对称合成。本综述总结了逆转ER的立体选择性和增强催化活性的方法,以及工程ER在光生物催化不对称合成中的新应用,此外还讨论了突变体在改善催化性能方面的现有分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Application of protein engineering to ene-reductase for the synthesis of chiral compounds through asymmetric reaction.

Ene-reductase (ER) has been widely applied for asymmetrical synthesis of chiral intermediates due to its substrate promiscuity, photoexcited reactivity, and excellent property with producing two chiral centers at a time. Natural ERs often exhibit the same stereoselectivity, and they need to be engineered for opposite configuration of chiral compounds. The hydrogenation process toward activated alkenes by ERs is composed of reductive half reaction and oxidative half reaction, which are dependent upon two cofactors NAD(P)H and flavin mononucleotide. The catalytic activity of ERs will be affected by the size of the substrate, the activating strength of the electron-withdrawing groups, redox potential of cofactors, and the loop flexibility around catalytic cavity. Currently, protein engineering to ERs has been successfully employed to enhance various catalytic properties, including photoexcited asymmetric synthesis. This review summarizes the approaches to reverse the stereoselectivity and enhance catalytic activity of ERs and new applications of the engineered ERs in photobiocatalytic asymmetric synthesis, besides the discussion with the existing molecular mechanisms of mutants regarding the improved catalytic performance.

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来源期刊
Critical Reviews in Biotechnology
Critical Reviews in Biotechnology 工程技术-生物工程与应用微生物
CiteScore
20.80
自引率
1.10%
发文量
71
审稿时长
4.8 months
期刊介绍: Biotechnological techniques, from fermentation to genetic manipulation, have become increasingly relevant to the food and beverage, fuel production, chemical and pharmaceutical, and waste management industries. Consequently, academic as well as industrial institutions need to keep abreast of the concepts, data, and methodologies evolved by continuing research. This journal provides a forum of critical evaluation of recent and current publications and, periodically, for state-of-the-art reports from various geographic areas around the world. Contributing authors are recognized experts in their fields, and each article is reviewed by an objective expert to ensure accuracy and objectivity of the presentation.
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