Chemical Industry and Engineering Progress ›› 2021, Vol. 40 ›› Issue (3): 1142-1160.DOI: 10.16085/j.issn.1000-6613.2020-2124

• Special column:Green biomanufacturing • Previous Articles     Next Articles

Stereoselective carbonyl reductases and their application in chiral alcohols synthesis

ZHANG Xiaojian1,2(), LIU Qian1,2, LIU Zhiqiang1,2(), ZHENG Yuguo1,2   

  1. 1.The National and Local Joint Engineering Research Center for Biomanufacturing of Chiral Chemicals, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China
    2.Key Laboratory of Bioorganic Synthesis of Zhejiang Province, College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China
  • Received:2020-10-22 Online:2021-03-17 Published:2021-03-05
  • Contact: LIU Zhiqiang

立体选择性羰基还原酶及其在手性醇合成中的应用

张晓健1,2(), 刘倩1,2, 柳志强1,2(), 郑裕国1,2   

  1. 1.浙江工业大学生物工程学院,手性生物制造国家地方联合工程研究中心,浙江 杭州 310014
    2.浙江工业大学 生物工程学院,浙江省生物有机合成重点实验室,浙江 杭州 310014
  • 通讯作者: 柳志强
  • 作者简介:张晓健(1980—),男,博士,讲师,研究方向为生物催化与转化。E-mail:xjzhang020@zjut.edu.cn
  • 基金资助:
    国家自然科学基金(21672190)

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: 

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