化工进展 ›› 2019, Vol. 38 ›› Issue (9): 4218-4226.DOI: 10.16085/j.issn.1000-6613.2019-0081

• 生物与医药化工 • 上一篇    下一篇

大肠杆菌乙酰辅酶A代谢调控及其应用研究进展

陈露1,2,3(),刘丁玉1,2,3,汪保卫1,2,3,赵玉姣1,2,3,贾广韬4,陈涛1,2,3,王智文1,2,3()   

  1. 1. 天津大学化工学院,天津 300350
    2. 天津大学系统生物工程教育部重点实验室,天津 300350
    3. 天津大学化工协同创新中心,天津 300350
    4. 潍坊医学院生物科学与生物技术学院,山东 潍坊 261053
  • 收稿日期:2019-01-11 出版日期:2019-09-05 发布日期:2019-09-05
  • 通讯作者: 王智文
  • 作者简介:陈露(1993—),女,硕士研究生。E-mail:chenlu123@tju.edu.cn
  • 基金资助:
    国家自然科学基金(NSFC-21776209);潍坊医学院教师公派教师国内访学项目(20187-32)

Advances in acetyl coenzyme A metabolic engineering with Escherichia coli

Lu CHEN1,2,3(),Dingyu LIU1,2,3,Baowei WANG1,2,3,Yu jiao ZHAO1,2,3,Guangtao JIA4,Tao CHEN1,2,3,Zhiwen WANG1,2,3()   

  1. 1. School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, China
    2. Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin 300350, China
    3. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300350, China
    4. College of Bioscience and Biotechnology, Weifang Medical College,Weifang 261053, Shandong, China
  • Received:2019-01-11 Online:2019-09-05 Published:2019-09-05
  • Contact: Zhiwen WANG

摘要:

利用生物法合成生物基化学品具有高效、绿色、可持续发展等优势。乙酰辅酶A作为细胞内物质代谢的重要中间产物,是利用生物转化法合成许多生物基化学品的重要前体,在微生物碳代谢过程中发挥着枢纽作用。本文综述了大肠杆菌乙酰辅酶A的合成、代谢调控策略及其重要应用,重点总结了乙酰辅酶A的合成途径及近期发展的提高乙酰辅酶A胞内通量的代谢调控策略,包括乙酸途径的代谢调控、丙酮酸合成乙酰辅酶A途径的代谢调控、中心碳代谢途径的代谢调控、β氧化合成乙酰辅酶A途径的代谢调控和乙酰辅酶A合成新途径的发掘,进一步展望了提高乙酰辅酶A供给的策略,利用基因组编辑技术构建合成乙酰辅酶A为前体化学品细胞工厂的方法。

关键词: 乙酰辅酶A, 大肠杆菌, 代谢工程, 通量

Abstract:

Biosynthesis of chemicals has the advantages of high efficiency, green and sustainable development. Acetyl coenzyme A, as an important intermediate of cellular metabolism in cells, is an important precursor for the synthesis of many biochemicals, and has played a vital role in the process of microbial carbon metabolism. Here we reviewed the synthesis and strategies of metabolic regulation of acetyl coenzyme A in Escherichia coli and its important applications. We also summarized the synthesis pathway of acetyl coenzyme A and the recent development of metabolic regulation strategies to increase the intracellular metabolic flux of acetyl coenzyme A production, these including metabolic regulation of the acetyl coenzyme A synthesized by acetic acid and pyruvate, metabolic regulation of the central carbon metabolic pathway and acetyl coenzyme A synthesized by beta oxidation pathway, and discovery of new pathways for acetyl coenzyme A synthesis. Finally, we prospected the feasible strategies of increasing acetyl coenzyme A supply and discussed methods of constructing cell factories for synthesizing acetyl coenzyme A as precursor chemicals by genome editing technology.

Key words: acetyl coenzyme A, Escherichia coli, metabolic engineering, flux

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