生物技术进展 ›› 2014, Vol. 4 ›› Issue (4): 229-235.DOI: 10.3969/j.issn.2095-2341.2014.04.01

• 进展评述 •    下一篇

超突变细胞在进化工程中的开发与应用

栾国栋,蔡真,李寅*   

  1. 中国科学院微生物研究所, 北京 100101
  • 收稿日期:2014-06-30 出版日期:2014-07-25 发布日期:2014-07-08
  • 通讯作者: 李寅,研究员,主要从事分子生理学和系统生物技术研究。E-mail:yli@im.ac.cn
  • 作者简介:栾国栋,博士,研究方向为工业生物技术。E-mail:luangd@qibebt.ac.cn。
  • 基金资助:

    国家973计划项目(2011CBA00800)资助。

Development and Application of Hypermutable Cells in Evolutionary Engineering

LUAN Guo-dong, CAI Zhen, LI Yin   

  1. Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
  • Received:2014-06-30 Online:2014-07-25 Published:2014-07-08

摘要: 通过进化工程技术改造微生物细胞的生理表型是生物技术和生物炼制领域的重要研究方向,但是现阶段的各种进化工程技术面临效率低或连续性差的问题。超突变细胞能够进行自发、连续的胞内诱变,将其应用于进化工程技术能够实现连续、高效的菌种改造。本文详细介绍了自然界中超突变细胞产生的遗传机制和相应的人工超突变细胞的构建策略,以及应用此类超突变系统在微生物细胞生理性能改造和蛋白质突变体文库高效构建上取得的进展。随着相关领域认识和技术的加强,未来人工超突变细胞的构建将继续向着不同维度上可控性、靶向性不断提高的方向发展,从而为细胞和蛋白的改造提供更强更优的进化动力。

关键词: 进化工程, 超突变细胞, 菌种改造, 定向进化

Abstract: Engineering microbial cellular phenotypes with evolutionary engineering approaches is a hot topic for biotechnology and biorefinery, however current evolutionary engineering approaches were restricted by low efficiency and discontinuity. Application of hypermutable cells in evolutionary engineering, with autonomous and continuous in vivo mutagenesis mechanisms, will enable continuous and effective strain improvements. In this paper, we introduced the genetic mechanisms for natural generation of hypermutable cells, the respective construction strategies of artificial hypermutable cells, and applications of such systems for improvements of microbial cellular phenotypes and construction of protein mutant libraries. With development of relative knowledge and technologies in this area, hypermutable microbial cells with improved capacity of controllable and targeting in vivo mutagenesis will be constructed in future, and provide more desirable evolutionary force for strain improvement and protein engineering.

Key words: evolutionary engineering, hypermutable cells, strain improvement, directed evolution