Design of a self-stable and population-controllable co-culture system in E. coli and its applications

Abstract Modular co-culture engineering has been applied to divide labor among different strains in the biomanufacturer of substances through complicated metabolic pathways. However, dynamic instability, uncontrollable population ratios, and lack of mathematical models have hindered its further application. In this study, we built a mathematical model and used it to design a self-stable co-culture system with adjustable population ratios of two engineered Escherichia coli strains. As an indicator product, the yield of chlorogenic acid was successfully increased by 16.5% by adjusting the population ratio in the system. This system provides a robust and scalable production platform for modular co-culture engineering. The co-culture system was confirmed to be a symbiotic system with high carbon atom economy for acetyl-CoA-derived chemicals by optimization of poly-β-hydroxybutyrate production, which was 2.82-fold higher than it was for wild-type E. coli. The conversion rate of glucose to poly-β-hydroxybutyrate also was 3.19-fold higher in the co-culture system. Our results provide new insights into possible future applications of co-culture systems.