Minimization of proteome reallocation explains metabolic transition in hierarchical utilization of carbon sources

Abstract

Cells 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 bacterium Bacillus coagulans displayed 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 of B. 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.

Model-guided strain engineering: bridges between design and learning in bioprocess development

“…For example, the use of ecGEM and dFBA in Chapter 5 led to the hypothesis that carbon catabolite repression is essential to obtain maximum growth rates when limitations at the proteome level are considered. A similar conclusion was recently reached by Liu et al, who based on ecGEM simulations followed by omic analysis, suggest the minimization of proteome reallocation to explain metabolic transitions in sequential utilization of mixed carbon sources of lactic acid bacteria [389]. Likewise, Elsemman et al developed a GEM with compartment-dependent proteome constraints that provided deeper insights into the physiology of S. cerevisiae [170], and Mishra et al developed a kinetic model of lipid metabolism revealing the presence of a futile cycle in triacylglycerol biosynthesis [118].…”