合成生物学 ›› 2021, Vol. 2 ›› Issue (1): 59-90.DOI: 10.12211/2096-8280.2020-071

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运动发酵单胞菌底盘细胞研究现状及展望

杨永富1, 耿碧男1, 宋皓月1, 何桥宁1, 何明雄2, 鲍杰3, 白凤武4, 杨世辉1   

  1. 1.湖北大学生命科学学院,省部共建生物催化与酶工程国家重点实验室,湖北省环境微生物工程技术研究中心,湖北 武汉  430062
    2.农业农村部沼气科学研究所,生物质能技术研究中心,四川 成都  610041
    3.华东理工大学生物工程学院,生物反应器工程国家重点实验室,上海  200237
    4.上海交通大学生命科学技术学院,微生物代谢国家重点实验室,上海  200240
  • 收稿日期:2020-07-05 修回日期:2020-10-01 出版日期:2021-02-28 发布日期:2021-03-12
  • 通讯作者: 白凤武,杨世辉
  • 作者简介:杨永富(1994—),男,博士研究生,研究方向为微生物系统生物学与合成生物学。E-mail:yongfu.yang@stu.hubu.edu.cn|耿碧男(1995—),女,博士研究生,研究方向为微生物基因组优化及合成生物学。E-mail:binangeng@stu.hubu.edu.cn|白凤武(1964—),男,博士,教授,研究方向为生物质资源生物炼制及微生物代谢工程。E-mail:fwbai@sjtu.edu.cn|杨世辉(1971—),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:Shihui.Yang@hubu.edu.cn
  • 基金资助:
    国家自然科学基金(21978071);国家重点研发计划(2018YFA0900300);浙江省引进培育领军型创新创业团队项目(2018R01014)

Progress and perspectives on developing Zymomonas mobilis as a chassis cell

Yongfu YANG1, Binan GENG1, Haoyue SONG1, Qiaoning HE1, Mingxiong HE2, Jie BAO3, Fengwu BAI4, Shihui YANG1   

  1. 1.State Key Laboratory of Biocatalysis and Enzyme Engineering,Environmental Microbial Technology Center of Hubei Province,School of Life Sciences,Hubei University,Wuhan 430062,Hubei,China
    2.Biomass Energy Technology Research Centre,Biogas Institute of Ministry of Agriculture,Chengdu 610041,Sichuan,China
    3.State Key Laboratory of Bioreactor Engineering,School of Biotechnology,East China University of Science and Technology,Shanghai 200237,China
    4.State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China
  • Received:2020-07-05 Revised:2020-10-01 Online:2021-02-28 Published:2021-03-12
  • Contact: Fengwu BAI,Shihui YANG

摘要:

运动发酵单胞菌(Zymomonas mobilis)是目前已知唯一能够在厌氧条件下利用Entner-Doudoroff(ED)途径代谢葡萄糖、果糖和蔗糖产乙醇的革兰氏阴性细菌,具有乙醇发酵速率高和对糖表观收率高、乙醇耐受性好及生物安全(generally regarded as safe,GRAS)等特点。基于合成生物学方法和代谢工程改造,可以作为纤维素乙醇及其他生物基产品生物炼制的细胞工厂。本文综述了运动发酵单胞菌独特的生理特点及其作为细胞工厂在不同领域的应用,重点介绍了构建运动发酵单胞菌作为底盘细胞,实现工业产品规模化经济生产涉及的系统生物学、合成生物学及代谢工程改造相关方法、技术与工具等方面的进展及瓶颈。同时探讨了持续开发、完善、应用高效精准的基因编辑技术、代谢途径精准时空调控方法及高通量自动筛选检测手段,在运动发酵单胞菌基因组精简优化以及生物固碳与固氮等方面取得的突破,推动合成生物学理论研究和实践应用的发展。

关键词: 运动发酵单胞菌, 合成生物学, 底盘细胞, 系统生物学, 基因编辑, 非模式微生物

Abstract:

Zymomonas mobilis, the only microorganism known to use the Entner-Doudoroff (ED) pathway anaerobically, can produce ethanol naturally from glucose, fructose and sucrose with many desirable traits such as ethanol production at high rate and yield and merit with biosafety (generally regarded as safe, GRAS), which has attracted more attention to be engineered as cell factories to produce biofuels and other bio-based products from lignocellulosic biomass. With the rapid development of novel technologies such as next-generation sequencing (NGS) and CRISPR-Cas genome editing as well as the accumulation of knowledge from studies on its physiology and modifications through metabolic engineering and systems biology, it is necessary to summarize accomplishments achieved recently to further explore the advantages of Z. mobilis, expediting the development and deployment of the robust synthetic microbial chass for the goals of "build to understand" and "build to apply" in the systems and synthetic biology era. In this review, we critically comment on the unique physiological characteristics of Z. mobilis and its potentials as a synthetic chassis to be engineered as microbial cell factories for producing diverse biochemicals economically, with a focus on the advances and challenges of developing efficient and effective tools and techniques for engineering this bacterium, taking advantages of methodologies developed with system biology and synthetic biology as well as metabolic engineering. We also prospect on future research for developing Z. mobilis as an attractive microbial chassis to be able to fix CO2 and N2 for biochemical production through genome optimization and metabolic engineering to advance the principles of synthetic biology and explore its potentials on biotechnological applications, which need unceasing effort to improve, develop and deploy efficient and effective genome editing tools, strategies for fine-tuning metabolic and regulatory pathways timely and spatially, as well as automatic high-throughput screening and quantification approaches.

Key words: Zymomonas mobilis, synthetics biology, chassis cell, systems biology, gene editing, non-model species

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