合成微生物组:当“合成生物学”遇见“微生物组学”

Synthetic microbiome: When “synthetic biology” meets “microbiomics”

合成微生物组是指运用合成生物学方法构建的功能菌群.合成微生物组以代谢通路模块化为核心特征,每个代谢模块的工作由一个菌株完成,从而实现多个菌株的分工与合作.与单菌株相比,合成微生物组具有降低菌株代谢负担与遗传改造难度、提供多样的元件表达平台、实现'即插即用'的模块替换等优势.在合成生物学与微生物组学快速发展、交汇融合的影响下,合成微生物组已成为近些年微生物领域新的研究热点,在生物合成平台化合物、复杂大分子以及生产生物燃料等方面具有广阔的应用前景.本文介绍了合成微生物组的设计原理与优势,总结了近些年的主要研究成果,阐述其目前面临的挑战与机遇,最后对其未来的发展进行展望.

Microbiomics focuses on the composition and function of microbial communities in a specific environment,while synthetic biology is an emerging discipline that uses engineering principles to elucidate,simulate and construct biological systems.The interdisciplinary branch of these disciplines has developed into an emerging subject called synthetic microbiomics,which has become a topic of interest in the field of microbiology.Distinct from the traditional functional microbiome,the synthetic microbiome refers to the functional microbiota constructed under the guidance of synthetic biology instead of the natural microbiota.The construction of a synthetic microbiome involves several steps,including model design,strain engineering,evaluation and optimization.Characterized by the modularization of metabolic pathways,the synthetic microbiome actualizes the cooperation of multiple strains with different functions.The synthetic microbiome has several advantages over monoculture in the case of synthesizing complex macromolecules and other platform chemicals.First,the metabolic burden of each strain is reduced as well as the difficulty of plasmid construction.Second,varied expression platforms are provided for multiple modules to increase the expression level of heterologous proteins.Third,modules could be easily added or substituted to obtain diverse products,and the relative metabolic intensity of each module is controlled through the inoculation ratio of co-cultured strains.Meanwhile,different parts of metabolic pathways are insulated by cell membrane,reducing the yield of byproducts.Finally,mixed substrates,such as lignocellulose hydrolysates,can be efficiently utilized by multiple strains,which cannot be used by a single strain due to substrate preference.Research on the synthetic microbiome has increased in recent years,yet most of these findings have not been applied in industry.The applications of the synthetic microbiome are normally concentrated on the production of three categories of products:platform compounds,complex macromolecules and biofuels.Other applications,such as bioelectrochemical systems and light-driven consortia,offer new energy resources and have significance in fundamental research on the symbiotic relationship of co-cultured strains.In many cases,the yield has remarkably improved thanks to the decrease of metabolic burdens caused by the division of labour.However,the stability and robustness of synthetic microbiomes remain as challenges.To improve stability,two design strategies could be taken into consideration:The quorum sensing system and the cross-feeding system.Improvements in genetic engineering and substrate utilization will enhance robustness.With the development of synthetic biology,more genetic editing and regulation tools will come into use,providing the possibility to construct stable and robust synthetic microbiomes comprising more strains.Once stability and robustness are attained,synthetic microbiome applications will likely spread throughout industry.