合成生物学 ›› 2023, Vol. 4 ›› Issue (4): 756-778.DOI: 10.12211/2096-8280.2023-032

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代谢工程改造微生物利用甲酸研究进展

程真真1,2, 张健1,2, 高聪1,2, 刘立明1,2, 陈修来1,2   

  1. 1.江南大学,食品科学与技术国家重点实验室,江苏 无锡 214122
    2.江南大学,食品安全国际合作联合实验室,江苏 无锡 214122
  • 收稿日期:2023-04-17 修回日期:2023-05-22 出版日期:2023-08-31 发布日期:2023-09-14
  • 通讯作者: 陈修来
  • 作者简介:程真真(2001—),女,学士。研究方向为微生物固碳途径的设计、构建与应用。E-mail:zzch0929@163.com
    陈修来(1985—),男,博士,教授。研究方向为微生物代谢工程与合成生物学。E-mail:xlchen@jiangnan.edu.cn
  • 基金资助:
    国家重点研发计划(2021YFC2103500);国家自然科学基金(22122806);江苏省自然科学基金(BK20211529);江南大学基本科研计划面上培育项目(JUSRP22031)

Progress in metabolic engineering of microorganisms for the utilization of formate

Zhenzhen CHENG1,2, Jian ZHANG1,2, Cong GAO1,2, Liming LIU1,2, Xiulai CHEN1,2   

  1. 1.State Key Laboratory of Food Science and Technology,Jiangnan University,Wuxi 214122,Jiangsu,China
    2.International Joint Laboratory on Food Safety,Jiangnan University,Wuxi 214122,Jiangsu,China
  • Received:2023-04-17 Revised:2023-05-22 Online:2023-08-31 Published:2023-09-14
  • Contact: Xiulai CHEN

摘要:

微生物利用甲酸生产高附加值产品,是实现碳资源回收利用与绿色产业发展的重要策略之一。然而,在微生物利用甲酸过程中存在甲酸利用效率偏低、细胞生长速率缓慢、目标代谢物产量不高等问题。为了解决上述问题,本文从甲酸利用的微生物、代谢路径与代谢工程策略三个方面,系统总结分析了代谢工程改造微生物利用甲酸的研究进展。在甲酸利用微生物方面,概述了天然甲酸利用微生物的代谢特点以及模式微生物的代谢工程改造潜能;在甲酸利用代谢路径方面,梳理了天然的甲酸利用路径、重构与优化的甲酸利用路径与人工的甲酸利用路径的关键步骤、能量/还原力消耗与特点;在甲酸利用代谢工程策略方面,阐述了提高甲酸同化效率与改善甲酸利用微生物细胞生长的关键方法。最后,从甲酸利用的微生物、代谢路径与代谢工程策略三个方面,展望了微生物利用甲酸的发展方向,为甲酸生物经济的发展奠定了基础。

关键词: 甲酸, 微生物, 代谢路径, 能量再生, 代谢工程

Abstract:

One carbon resources are expected to become the next generation raw materials for the production of high value-added chemicals to achieve the recycling and utilization of carbon resources and promote the development of green industries. To achieve this aim, microbial utilization of formate produced from various one carbon resources, is one of the important strategies to build a green and sustainable platform for one-carbon biomanufacturing. However, there are many problems in the process of microbial utilization of formate, such as the low efficiency of formate utilization, the slow growth rate of formate-utilizing microorganisms, and the low yield of target metabolites and so on. To solve these problems, in this paper we systematically summarize and analyze the research progress in metabolic engineering of microorganisms for the utilization of formate from following three aspects: formate-utilizing microorganisms, metabolic pathways and metabolic engineering strategies. For formate-utilizing microorganisms, we summarize the metabolic characteristics and applicative advantages of natural formate-utilizing microorganisms, as well as the potential and advantages of model microorganisms for the application of metabolic engineering. For formate-utilizing metabolic pathways, we review the key steps, energy/reducing power consumption and characteristics of natural formate-utilizing pathways, reconstruction and optimization of formate-utilizing pathways and artificial formate-utilizing pathways, and then discuss the potential of metabolic engineering modification of these pathways. For formate-utilizing metabolic engineering strategies, we describe the useful strategies to improve the metabolic efficiency of formate assimilation pathways, such as optimizing the expression level of pathway genes, engineering key pathway enzymes, blocking the competitive pathways, reconstructing cofactor regeneration system, and modular pathway engineering, and then summarize the key approaches to improve the cell growth of formate-utilizing microorganisms, such as adaptive laboratory evolution, enhancing the cell growth of formatotrophs and improving the ability of microorganisms to synergistically utilize formate. Finally, we prospect the developmental direction of microbial utilization of formate from three aspects of formate-utilizing microorganisms, metabolic pathways and metabolic engineering strategies, which would lay the foundation for the development of formate bio-economy. {L-End}

Key words: formate, microorganisms, metabolic pathway, energy regeneration, metabolic engineering

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