羰基还原酶及其催化不对称合成大基团手性羟基类化合物的研究进展  

Stereoselective carbonyl reductases and their roles in asymmetric synthesis of bulky chiral hydroxyl compounds

作　　者：聂尧[1] 徐岩 NIE Yao;XU Yan(Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China)

机构地区：[1]江南大学生物工程学院工业生物技术教育部重点实验室,无锡214122

出　　处：《中国科学：生命科学》2019年第5期595-604,共10页Scientia Sinica(Vitae)

基　　金：国家自然科学基金(批准号:21336009;21676120);江苏省自然科学基金(批准号:BK20151124)资助

摘　　要：手性羟基化合物以其独特的光、热和化学性质广泛应用于医药、农药、精细化工、功能材料等行业.立体专一性羰基还原酶能够直接针对关键手性位点催化不对称还原潜手性底物获得目的手性产物.基于羰基还原酶的底物多样性,具有不同化学结构和功能的醇类、酯类、氨基酸、环氧化合物等重要手性中间体能够通过不对称还原途径实现单一光学活性对映体的高效制备.然而,针对具有应用价值的含有大基团、结构复杂的潜手性羰基化合物,已知的羰基还原酶通常催化活性较低.本文综述了生物催化不对称氧化还原反应的特点和规律及其关键立体选择性羰基还原酶的性质和结构特征,并在此基础上,重点针对大基团手性羟基化合物的不对称合成,总结了羰基还原酶及其催化系统开发和应用的研究进展,并进一步提出解决该关键问题的主要发展策略.Chiral hydroxyl compounds have been widely used in pharmaceutical, agrochemical, fine chemicals, and functional materials industries, due to their unique physical and chemical properties. Stereoselective carbonyl reductases can be efficiently applied to catalyze asymmetric synthesis of chiral hydroxyl compounds with high optical purity from directed reduction of prochiral carbonyl group of the corresponding keto substrates. Based on the diversity of substrates, single enantiomers of various chiral hydroxyl compounds, including chiral alcohols, hydroxyl esters, and hydroxyl amino acids, can be prepared through carbonyl reductasecatalyzed asymmetric reduction in a high efficiency. However, most of the available carbonyl reductases only exhibit low activity towards the substrates involving bulky groups. This review summarizes the basic traits and principles of biocatalytic asymmetric oxidoreductions, and the key characteristics and structure-function relationship of stereoselective carbonyl reductases. In addition, the carbonyl reductases and their systems for asymmetric synthesis of bulky chiral hydroxyl compounds are also addressed, and the potential strategies targeting the critical issue are further discussed.

关 键 词：羰基还原酶 立体选择性 手性羟基化合物 不对称合成 大基团底物 

分 类 号：Q55[生物学—生物化学]