合成生物学 ›› 2020, Vol. 1 ›› Issue (4): 427-439.DOI: 10.12211/2096-8280.2020-045

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智能抗逆微生物细胞工厂与绿色生物制造

许可1, 王靖楠2, 李春1,2   

  1. 1.清华大学化学工程系,工业生物催化教育部重点实验室,北京 100084
    2.北京理工大学化学与化工学院,生物化工研究所,北京 100081
  • 收稿日期:2020-04-09 修回日期:2020-05-02 出版日期:2020-08-31 发布日期:2020-10-09
  • 通讯作者: 李春
  • 作者简介:许可(1983— ),男,博士,助理研究员,研究方向为代谢工程与合成生物学。E-mail: xuke528@tsinghua.edu.cn|李春(1970— ),男,博士生导师,教授,研究方向为代谢工程与合成生物学。E-mail: lichun@tsinghua.edu.cn
  • 基金资助:
    国家自然科学基金(22078171)

Intelligent microbial cell factory with tolerance for green biological manufacturing

Ke XU1, Jingnan WANG2, Chun LI1,2   

  1. 1.Key Lab for Industrial Biocatalysis,Ministry of Education,Department of Chemical Engineering,Tsinghua University,Beijing 100084,China
    2.Department of Biochemical Engineering,School of Chemistry and Chemical Engineering,Beijing Institute of Technology,Beijing 100081,China
  • Received:2020-04-09 Revised:2020-05-02 Online:2020-08-31 Published:2020-10-09
  • Contact: Chun LI

摘要:

绿色生物制造作为新的工业模式,在其发酵过程中,生物转化效率往往被环境变化或代谢失衡引起的一系列逆境胁迫所限制,导致细胞工厂生长缓慢、产量下降、生产能耗大幅升高等,严重制约着产业的发展。构建在多重胁迫因子条件下具有良好表现的智能抗逆微生物细胞工厂,为绿色生物制造迎来了新的机遇。本文介绍了绿色生物制造过程中微生物细胞工厂面临的胁迫因子及其胁迫机理,综述了提高微生物细胞工厂耐受性的主要策略,包括非理性技术增强细胞自身防御系统及以工程化思维、借助合成生物学技术有针对性地设计并集成抗逆基因线路,重编程微生物细胞工厂提高其抗逆能力,最后对智能抗逆微生物细胞工厂在生物医药、大宗化学品、食品等绿色生物制造涉及领域的应用进行展望。期待本文为实现细胞工厂对环境胁迫的应答与智能调节提供新的研究思路。

关键词: 逆境胁迫, 抗逆基因线路, 智能响应, 微生物细胞工厂, 绿色生物制造

Abstract:

The current development model has led to an unsustainable supply of petroleum and global climate change, which present an urgent need for switching the traditional 'take-make-dispose' economy to a renewable one with a reduced carbon footprint by introducing biological systems into the traditional chemical manufacturing to develop green, renewable and safe biological manufacturing. Green biological manufacturing is a new industrial model, and the bio-transformation efficiency is often limited by a series of stresses caused by environmental changes or metabolic imbalance, which lead to the slow growth of cells, decline of production, and increase of energy consumption. All these ultimately make biological manufacturing less competitive economically. How to minimize the impact of stresses on microbial cell factory is of great significance, which creates a new opportunity for building an intelligent microbial cell factory with tolerance under multiple stress conditions for green biological manufacturing. This review not only introduces stress factors and their action mechanism to microbial cell factories in the process of biological manufacturing, but also summarizes commonly used strategies to improve the tolerance of microbial cells, including the random and semirational technologies to improve the self-defense system of cells. With the help of engineering thinking and synthetic biology technology to design and integrate tolerant gene circuits for reprogramming metabolism, in particular the development of intelligent microbial cell factory, stress tolerance can be further improved. It is expected that this review can provide new ideas for the intelligent response and regulation of microbial cells to environmental stresses.

Key words: stress, tolerant gene circuits, intelligent response, microbial cell factory, green biological manufacturing

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