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

Abstract

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 by-products. 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.