人工多菌体系的设计与构建：合成生物学研究新前沿

doi:10.12211/2096-8280.2021-031

合成生物学 ›› 2021, Vol. 2 ›› Issue (4): 635-650.DOI: 10.12211/2096-8280.2021-031

人工多菌体系的设计与构建：合成生物学研究新前沿

刘裕¹, 韦惠玲¹, 刘骥翔¹, 王少杰^1,², 苏海佳¹

^1.北京化工大学化学资源工程国家重点实验室，北京生物过程重点实验室，北京软物质科学与工程先进创新中心，北京　100029
^2.上海交通大学电子信息与电子工程学院纳米生物医学与工程研究所，上海　200240

收稿日期:2021-03-10 修回日期:2021-05-17 出版日期:2021-08-31 发布日期:2021-09-10
通讯作者: 王少杰,苏海佳
作者简介:刘裕（1997—），女，硕士研究生。研究方向为基于合成生物学的人工多菌体系构建。E-mail：983381329@qq.com|王少杰（1991—），男，博士后。研究方向为合成生物学与生物能源。E-mail：wangshaojie0711@sjtu.edu.cn|苏海佳（1970—），女，教授，博士生导师。研究方向为合成生物学、生物分离、工业水处理、生物环境材料等。E-mail：suhj@mail.buct.edu.cn
基金资助:
国家自然科学基金(21838001);国家重点研发计划(2018YFA0902200);中央高校基础研究经费(JD2007);中国博士后科学基金(2020M681302)

Design and progress of synthetic consortia： a new frontier in synthetic biology

Yu LIU¹, Huiling WEI¹, Jixiang LIU¹, Shaojie WANG^1,², Haijia SU¹

^1.State Key Laboratory of Chemical Resource Engineering，Beijing Key Laboratory of Bioprocess，Beijing Advanced Innovation Center for Soft Matter Science and Engineering，Beijing University of Chemical Technology，Beijing 100029，China
^2.Institute of Nano Biomedicine and Engineering，School of Electronic Information and Electrical Engineering，Shanghai Jiao Tong University，Shanghai 200240，China

Received:2021-03-10 Revised:2021-05-17 Online:2021-08-31 Published:2021-09-10
Contact: Shaojie WANG,Haijia SU

摘要/Abstract

摘要：

合成生物学的飞速发展拓展了单菌体系的功能。然而在重组菌株中，异源途径的过表达会增加底盘细胞的代谢压力，导致细胞中能量分配失衡，进而对底盘细胞的正常生长和目标产物的生物合成产生不利影响。作为一种更加新颖有效的生物合成平台，人工多菌体系在为目标产物的生物合成提供多样且适配的表达环境的同时，有效地分配底盘细胞的代谢负担，使得途径的全局调控更加灵活。本文明确指出了人工多菌体系是合成生物学领域中一个新的研究前沿，并以多菌体系的设计和构建为文章主旨，通过详细比较单菌体系和人工多菌体系的优缺点，突出人工多菌体系在生物合成中的优势，同时以人工多菌体系在近几年生物合成中的最新进展为实例，从途径分工的理性设计、菌群互作关系的理性设计、功能菌群时空有序分布以及基于模型算法指导下的多菌体系理性构建4个方面对人工多菌体系的设计原则和构建方法进行详细介绍。最后根据目前人工多菌体系存在的问题提出了有关人工多菌体系全局调控的方法，并对人工多菌体系的设计、构建以及在各种生物产品合成中的发展进行了展望。

关键词: 人工多菌体系, 天然产物合成, 代谢工程, 生物能源, 生物合成

Abstract:

Metabolic engineering and synthetic biology have enabled efficient bioproduct synthesis in mono-microbial culture by pathway reconstruction. In spite of that, in the demand of increasing bioproduction, mono-culture has gradually showed some limitations in the tasks of accomplishing complicated biosynthesis and achieving high efficiency. The expression of multi-step biosynthetic pathways in one cell may greatly increase the metabolic burden of the host, which may result in a huge imbalance between cell growth and gene expression and thus decrease the titer of bioproduct. Synthetic consortia have been designed as an alternative effective biosynthesis system to distribute complex functions and pathways into different cells or species. In this article, the advantages of the synthetic consortia are summarized, including providing better environment for different functional genes expression, balancing working intensity, reducing metabolic burden, plug-and-play and eliminating feedback inhibition. Based on the above advantages and taking recent advances in biosynthesis studies utilizing synthetic consortia systems as case studies, some design principles involving functional modules, synergism and robustness are put forward in this article. To be specific, it is necessary to reasonably divide and allocate functional modules into different strains in the system. With appropriate chassis strains, it will be beneficial to establish synergistic substrate utilization and mutually beneficial symbiosis between different strains, which could increase the connections between functional modules as well as the interactions between chassis strains. Moreover, the application of population control strategies will efficiently increase system robustness. Under the premise of material exchange, spatiotemporal distribution in synthetic consortia is conducive for better coordination and interaction between strains. In addition, modeling on synthetic consortia systems have been initiated to simulate bioproduct process and optimize consortia construction. In response to the current problems, some global regulation methods and prospectives for synthetic consortia are also proposed in three aspects: internal optimization, external reinforcement, and mathematical modeling.

Key words: synthetic consortia, natural product synthesis, metabolic engineering, bioenergy, biosynthesis

中图分类号:

Q812

刘裕, 韦惠玲, 刘骥翔, 王少杰, 苏海佳. 人工多菌体系的设计与构建：合成生物学研究新前沿[J]. 合成生物学, 2021, 2(4): 635-650.

Yu LIU, Huiling WEI, Jixiang LIU, Shaojie WANG, Haijia SU. Design and progress of synthetic consortia： a new frontier in synthetic biology[J]. Synthetic Biology Journal, 2021, 2(4): 635-650.

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人工多菌体系的设计与构建：合成生物学研究新前沿

Design and progress of synthetic consortia： a new frontier in synthetic biology

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