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

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