Rational construction of synthetic consortia: Key considerations and model-based methods for guiding the development of a novel biosynthesis platform

The rapid development of synthetic biology has significantly improved the capabilities of mono-culture systems in converting different substrates into various value-added bio-chemicals through metabolic engineering. However, overexpression of biosynthetic pathways in recombinant strains can impose a heavy metabolic burden on the host, resulting in imbalanced energy distribution and negatively affecting both cell growth and biosynthesis capacity. Synthetic consortia, consisting of two or more microbial species or strains with complementary functions, have emerged as a promising and efficient platform to alleviate the metabolic burden and increase product yield. However, research on synthetic consortia is still in its infancy, with numerous challenges regarding the design and construction of stable synthetic consortia. This review provides a comprehensive comparison of the advantages and disadvantages of mono-culture systems and synthetic consortia. Key considerations for engineering synthetic consortia based on recent advances are summarized, and simulation and computational tools for guiding the advancement of synthetic consortia are discussed. Moreover, further development of more efficient and cost-effective synthetic consortia with emerging technologies such as artificial intelligence and machine learning is highlighted.