Dynamic minimization of proteome reallocation explains metabolic transition in hierarchical utilization of mixed carbon sources

Abstract

AbstractCells choose between alternative pathways in metabolic networks under diverse environmental conditions, but the principles governing the choice are insufficiently understood, especially in response to dynamically changing conditions. Here we observed that a lactic acid bacteriumBacillus coagulansdisplayed homolactic fermentation on glucose or trehalose as the sole carbon source, but transitioned from homolactic to heterolactic fermentation during the hierarchical utilization of glucose and trehalose when growing on the mixture. We simulated the observation by dynamic minimization of reallocation of proteome (dMORP) using an enzyme-constrained genome-scale metabolic model ofB. coagulans, which coincided with our multi-omics data. Moreover, we evolved strains to co-utilize mixed carbon sources, circumventing the hierarchical utilization and inactivating the choice of heterolactic fermentation. Altogether, the findings suggest that upon rapid environmental changes bacteria tend to minimize proteome reallocation and accordingly adjust metabolism, and dMORP would be useful in simulating and understanding cellular dynamics.