Stereoselective carbonyl reductases and their application in chiral alcohols synthesis

doi:10.16085/j.issn.1000-6613.2020-2124

Abstract

Abstract:

Chiral alcohols are important and versatile building blocks for the preparation of a variety of pharmaceuticals and fine chemicals. It is of great value to develop green production technologies for chiral alcohols using carbonyl reductase as the biocatalyst, which attracts widely concentration around the world. This article reviews the discovery and classification, the mechanism of activity and stereoselectivity, enzyme screening and molecular modification technologies, cofactor regeneration, as well as the biosynthesis of pharmaceutical intermediates and fine chemicals catalyzed by stereoselective carbonyl reductases. The development in enzymatic production of anticholesterol drugs, antibiotics, antineoplastics, antidepressants, antiepileptics, etc. is investigated. The review contributes to the theoretical and technical guidance for the development of stereoselective carbonyl reductase biocatalysts and the biosynthesis of chiral pharmaceutical intermediates and fine chemicals.

Key words: biocatalysis, carbonyl reductase, asymmetric reduction, stereoselectivity, chiral alcohols

摘要：

手性醇是重要的医药中间体与精细化工品，立体选择性羰基还原酶催化制备手性醇具有重要的研究与应用价值，受到国内外科学家和工程师的高度关注。本文主要围绕羰基还原酶的发现与分类、催化羰基还原反应的活性与立体选择性机制、酶的筛选挖掘与分子改造技术、辅酶还原型烟酰胺腺嘌呤二核苷酸（磷酸）的再生方法、羰基还原酶催化合成手性醇医药中间体与精细化学品技术开发与应用等方面展开综述。重点阐述了羰基还原酶催化制备降血脂、抗细菌或病毒感染、抗肿瘤、抗抑郁症、抗癫痫等重要疾病治疗药物中间体及脂肪族、芳香族手性醇精细化工品的国内外技术进展与应用，为高效能立体选择性生物催化剂的创制和手性化合物的生物合成提供理论借鉴和成功范例。

关键词: 生物催化, 羰基还原酶, 不对称还原, 立体选择性, 手性醇

CLC Number:

ZHANG Xiaojian, LIU Qian, LIU Zhiqiang, ZHENG Yuguo. Stereoselective carbonyl reductases and their application in chiral alcohols synthesis[J]. Chemical Industry and Engineering Progress, 2021, 40(3): 1142-1160.

张晓健, 刘倩, 柳志强, 郑裕国. 立体选择性羰基还原酶及其在手性醇合成中的应用[J]. 化工进展, 2021, 40(3): 1142-1160.

Figures/Tables 17

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辅底物再生体系	反应式
甲酸-FDH
异丙醇-ADH
葡萄糖-GDH
葡萄糖-6-磷酸-GDPH

辅底物再生体系	反应式
甲酸-FDH
异丙醇-ADH
葡萄糖-GDH
葡萄糖-6-磷酸-GDPH

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