(643e) Genetically Programmable Assembly of Microbial Communities for Enhanced Biosynthetic Efficiency

Microbial consortia are increasingly used to perform multi-step biosynthetic transformations that are difficult to perform in a single organism. However, in simple co-culture systems, intermediate metabolites are rapidly diluted by the extracellular medium, leading to reduced rates of downstream biosynthetic steps. Close proximity of microbes to one another may enable metabolite exchange between cells before they are diluted by the bulk culture, and may thereby increase the yield of the final product. In this work, we have engineered microbes to display surface proteins that induce the formation of large (up to 100 µm diameter) clusters. Reaction-diffusion modeling of biological transformations within these clusters shows that cluster size is an important tunable parameter for controlling the efficiency of multicellular biosynthetic cascades, and experiments have shown that cluster size can be controlled by the stoichiometry of hetero-associating surface proteins. By understanding substrate diffusion and the kinetics of each biosynthetic step, we are developing design rules to optimize the spatial organization of microbial consortia to maximize substrate conversion and product yield. In the future, the techniques under development in this work may allow reactions that normally must be done under separate conditions to be performed in a single bioreactor.