Metabolic Design Principles for Engineering Synthetic Microbial Communities

Biotechnological solutions to some of the key economic and societal challenges will require the engineering of multi-species systems, that can fully exploit the biochemical potential of the microbial world, and that can allow novel applications such as artificial gut, synthetic soil, waste-to-value conversion, and ecosystem functions in space missions. It is unlikely that the current focus on engineering genetic circuits in model organisms on its own can achieve these high level applications of “microbial engines” composed of multiple microbial species that are biochemically and industrially relevant. To successfully carry out this kind of complex engineering, synthetic biology will need to establish the design principles governing microbial interactions and develop the experimental tools for their characterisation and manipulation.

Here, I will describe our ongoing efforts in discovering the reasons for metabolic interactions among microbes. I will argue that these metabolic interactions can be understood as an emergent property of the biochemical environment and associated thermodynamics within a multi-species system. Particularly, results from our recent research has shown that the thermodynamic basis of microbial growth can lead to co-existence, even under conditions that are kinetically predicted to lead to competition-driven exclusion. This thermodynamic inhibition can have significant consequences for the engineering of multi-species system. I will illustrate these with examples from our ongoing experimental work in establishing metabolic interaction motifs among biochemically and biotechnologically relevant microbes.