化工进展 ›› 2019, Vol. 38 ›› Issue (01): 606-614.DOI: 10.16085/j.issn.1000-6613.2018-1136

• 生物与医药化工 • 上一篇    下一篇

底物特异性的生物催化与酶设计改造

姜恬1(),冯旭东2,李岩1,李春1,2()   

  1. 1. 北京理工大学生命学院,北京 100081
    2. 北京理工大学化学与化工学院,北京 100081
  • 收稿日期:2018-05-31 修回日期:2018-08-23 出版日期:2019-01-05 发布日期:2019-01-05
  • 通讯作者: 李春
  • 作者简介:姜恬(1993—),女,硕士研究生,研究方向为酶工程。E-mail:<email>jiangtiantian1002@163.com</email>。|李春,教授,博士生导师,研究方向为生物催化与酶工程、代谢工程与合成生物学。E-mail:<email>lichun@bit.edu.cn</email>。
  • 基金资助:
    国家自然科学基金(21506011);国家杰出青年科学基金(21425624);国家自然科学基金(21506011);国家杰出青年科学基金(21425624)。

The biocatalysis and enzyme modification of substrate specificity

Tian JIANG1(),Xudong FENG2,Yan LI1,Chu LI1,2()   

  1. 1. School of Life Science, Beijing Institute of Technology, Beijing 100081, China
    2. School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China
  • Received:2018-05-31 Revised:2018-08-23 Online:2019-01-05 Published:2019-01-05
  • Contact: Chu LI

摘要:

随着生物产业的发展,生物酶催化发挥着越来越重要的作用。然而,部分酶在应用过程中仍然存在诸多问题,影响了生物催化的进一步发展。本文以酶的底物特异性为切入点,回顾了酶的专一性、高效性和环保性;介绍了酶在药物合成和天然产物改性领域的应用以及所遇到的问题;综述了酶的底物特异性改造过程中各种方法的应用,包括化学修饰、非理性和理性设计。化学修饰作为一种直观的修饰方法,通过化学反应对酶分子进行改造;非理性设计是利用易错PCR和DNA Shuffling等手段获得底物特异性提高的突变体;理性设计是基于序列和结构信息对酶分子进行改造。本文从重塑活性口袋提高酶的底物特异性和重塑活性口袋改变酶促反应类型两个方面出发,详述了理性设计改变酶的底物特异性的方法,为酶的特异性改造提供借鉴。

关键词: 生物催化, 酶设计, 底物特异性, 分子改造

Abstract:

Enzymatic catalysis plays an increasing role in the development of bio-industry. However, there are still many problems in the application of some enzymes, which hinder the development of biocatalysis. This paper focused on the enzyme substrate specificity and reviewed the advantages of enzymes, such as high specificity, increased efficiency, and environmentally-friendly process. The applications of enzymes in fine chemistry and pharmaceutical synthesis were introduced. The paper also summarized the current methods used in engineering of enzyme substrate specificity, including chemical modification, irrational and rational design. Chemical reaction was a direct-viewing method applied in enzyme modification. Irrational design was often employed to obtain the better mutants with increased substrate specificity through error-prone PCR and DNA shuffling. In the rational design, enzyme engineering was based on their sequences and structures. Starting from reshaping the active pockets for increasing the substrate specificity and changing the enzymatic reaction type, this paper elaborated the methods of rational design to enhance the substrate specificity and provided a reference for future substrate specificity engineering.

Key words: biocatalysis, design of enzyme, substrate specificity, molecular modification

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