• 特约评述 •

亚胺还原酶在手性胺合成中的应用

1. 上海交通大学生命科学技术学院，微生物代谢国家重点实验室，教育部代谢与发育科学国际合作联合实验室，上海 200240
• 收稿日期:2021-05-01 修回日期:2021-07-27 出版日期:2022-06-30 发布日期:2022-07-13
• 通讯作者: 瞿旭东
• 作者简介:杨璐（1993—），女，博士研究生。研究方向为杂环类生物碱的生物合成研究及酶工程改造。E-mail：yl2020@sjtu.edu.cn|瞿旭东（1980—），男，教授，博士生导师。研究方向为生物合成与生物催化。E-mail：quxd19@sjtu.edu.cn
• 基金资助:
国家自然科学基金(31970054);国家重点研发计划(2018YFC1706200)

Application of imine reductase in the synthesis of chiral amines

Lu YANG, Xudong QU

1. State Key Laboratory of Microbial Metabolism，School of Life Sciences and Biotechnology，Shanghai Jiao Tong University，Shanghai 200240，China
Chiral amines with bioactivities are important chiral auxiliaries, and also key intermediates for the synthesis of many natural products and chiral drugs. Among the top 200 drugs for market revenues in 2019, more than 30% contain chiral amine structures. Therefore, the development of efficient and effective methods to synthesize chiral amine compounds is of interest for research. Due to its high efficiency, environmental friendliness and economic competitiveness, more attention has been paid on the enzyme-catalyzed production of chiral amines by academia and industry. Imine reductases (IREDs) reviewed in this article are a class of NAD(P) H-dependent oxidoreductases that catalyze asymmetric reduction of imines to chiral amines. The reduction of C$???????$N bonds constitutes a physiological reaction present in a number of biosynthetic pathways, leading to a variety of metabolites. The imine reductases have excellent characteristics such as high catalytic efficiency, strong regioselectivity and stereoselectivity, etc., which stand out among many other methods for the synthesis of chiral amines, and attract attention and enthusiasm of many researchers. In the past decade, with the rapid development of bioinformatics, structural biology, high-throughput screening approaches and the continuous expansion of the gene databases, many imine reductases with different functions have been identified. Significant achievements have been made in the discovery of IREDs, protein engineering and multi-enzyme cascade applications, among which some successful modification cases have industrial application potentials. This review summarizes the structural characteristics, catalytic mechanisms and applications of IREDs, with emphasis on their protein engineering and applications in multi-enzyme cascade reactions, as well as the bottleneck, breakthrough and progress in asymmetric catalytic chiral amine biosynthesis. In addition, the challenges and potentials of the enzymatic synthesis of chiral amine compounds for industrial production, and the importance of novel artificial biosynthesis pathway design to overcome these challenges are highlighted.