(711f) Engineered Substrate Specificity for Prebiotic Control of Microbial Community Population and Gene Expression

Optimal production of high-value chemicals often requires expression of many genes in particular sequences, the metabolic burden of which can overwhelm an engineered strain. To address this, researchers have begun to assemble artificial microbial communities which can divide labor, synergistically improving production. However, control of the population and expression dynamics in these consortia can be difficult. In this work, we use prebiotic complex carbohydrate compounds, the human milk oligosaccharides (HMOs), to control population dynamics and protein expression in mixed cultures of E. coli. We accomplish this using a unique whole-cell biosensor which provides linkage-specific, quantitative detection of various HMOs. The ability to utilize these complex substrates orthogonally controls growth rate or protein expression of particular strains in mixed populations. This work lays the groundwork for the application of directed evolution to biosynthesis of complex carbohydrates as well as the prebiotic manipulation of population dynamics in natural and engineered microbial communities.