化工进展 ›› 2021, Vol. 40 ›› Issue (7): 3932-3941.DOI: 10.16085/j.issn.1000-6613.2020-1607

• 生物与医药化工 • 上一篇    下一篇

甲基营养型大肠杆菌构建策略的研究进展

陶雨萱1(), 张尚杰1, 景艺文1, 信丰学1,2, 董维亮1,2, 周杰1,2, 蒋羽佳1, 章文明1,2(), 姜岷1,2()   

  1. 1.南京工业大学生物与制药工程学院, 材料化学工程国家重点实验室,江苏 南京 211816
    2.南京工业大学, 江苏先进生物与化学制造协同创新中心(SICAM),江苏 南京 211816
  • 收稿日期:2020-08-12 修回日期:2020-10-26 出版日期:2021-07-06 发布日期:2021-07-19
  • 通讯作者: 章文明,姜岷
  • 作者简介:陶雨萱(1997—),女,硕士研究生,主要研究方向为抗逆元件的挖掘与性能表征。E-mail:15106192105@163.com
  • 基金资助:
    国家重点研发计划(2018YFA0901500);国家自然科学基金(22078151)

Recent advances in the construction strategy of methylotrophic Escherichia coli

TAO Yuxuan1(), ZHANG Shangjie1, JING Yiwen1, XIN Fengxue1,2, DONG Weiliang1,2, ZHOU Jie1,2, JIANG Yujia1, ZHANG Wenming1,2(), JIANG Min1,2()   

  1. 1.State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing 211816, Jiangsu, China
    2.Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing 211816, Jiangsu, China
  • Received:2020-08-12 Revised:2020-10-26 Online:2021-07-06 Published:2021-07-19
  • Contact: ZHANG Wenming,JIANG Min

摘要:

利用微生物细胞工厂实现原料转化和产品合成是绿色生物制造的核心。然而,当前生物制造仍以富含糖类的谷物粮食为主要原料,存在“与民争粮”的争议,亟需开发非粮原料。甲醇作为煤化工产业中的重要产品,具有来源广、价格低、还原性强等优势,有替代粮食原料的潜力。天然甲基营养菌可利用甲醇生产单细胞蛋白和各种氨基酸,但存在理论收率低、遗传改造工具不足等缺点。随着合成生物学的发展,以大肠杆菌等模式生物作为底盘细胞构建人工甲基营养菌,实现甲醇到各种化学品的生产已成为研究热点。本文总结了多种甲基营养型大肠杆菌的构建策略,明确了影响天然路径代谢的关键因素与代谢过程中的重要中间产物,概括了各种天然路径在大肠杆菌中的优化策略与人工新路径的构建方法,并对工程菌株的优化提出了展望。

关键词: 甲醇, 大肠杆菌, 合成生物学, 工业生物技术, 代谢途径, 甲基营养型

Abstract:

The use of microbial cell factories to realize the transformation of raw materials and the synthesis of products is the core of green biological manufacturing. However, the current bio-manufacturing mainly uses sugar-rich grains as the raw material, leading to a controversy of "competing with the people for food". As a result, there is an urgent need to develop non-food raw materials. As a main product of coal chemical industry, methanol has the advantages of abundant sources, low price, and high degree of reduction, indicating that it has the potential to replace food raw materials. Natural methylotrophs have been used to produce single-cell protein and various amino acids from methanol. However, there are many disadvantages such as low theoretic yield and inefficient genetic tool. With the development of synthetic biology, the use of model organisms such as Escherichia coli as chassis cells to construct artificial methylotrophic bacteria and realize the production of methanol to various chemicals has become a research hotspot. In this review, we firstly summarized the construction strategies of a variety of methylotrophic Escherichia coli. Then, the key factors affecting the metabolism of natural pathways and important intermediate metabolites were clarified. Moreover, various methods for optimizing natural methanol metabolic pathways and constructing new artificial pathways were discussed. And we put forward a prospect for the optimization of methanol utilization by engineering strains.

Key words: methanol, Escherichia coli, synthetic biology, industrial biotechnology, metabolic pathway, methylotrophic

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