Microbial Division of Labor for Mixed Sugar Fermentation

The feedstocks of microbial fermentation are usually present in a form of mixed substrates. Full utilization of such mixtures can be achieved by a 'superbug' strain capable of simultaneous multi-substrate consumption or, alternatively, by a consortium of strains through a division of labor (DOL) whereby each member specializes in utilizing one specific substrate. Conceptually, the latter allows to reduce the high metabolic burden and pathway crosstalk, thus promising a higher fermentation efficiency and a better overall productivity. However, it remains unclear whether DOL indeed offers these advantages over single strains and under what circumstances DOL is superior for mixed substrate fermentation. In this study, we develop a theoretical framework for microbial mixed-sugar fermentation and use it to compare the performances of the superbug and DOL strategies in chemostats. Through the analysis from a minimal model to systems with increasing complexity, we find that the conditions favorable to DOL can be specified by a general rule regarding the metabolic burden and pathway crosstalk effect of superbug, inflow concentrations of substrates, and dilution rate of the chemostat. Our work provides quantitative insights into the design principles of microbial consortia for multi-substrate fermentation.