Thermodynamic constraints on cross-feeding in bacterial population

Overflow metabolism refers to the strategy of cells using fermentation instead of the more energetically-efficient respiration, even when the oxygen is available. Cross-feeding between two bacterial strains growing on a single primary carbon source can be established when one bacterial strain consumes overflow metabolites excreted by the other bacterial strain. Many overflow pathways are thermodynamically controlled and thermodynamic constraints on them are not included to consider the cross-feeding of overflow metabolites between two strains in the past. Motivated by experimental results of acetate cross-feeding polymorphism, in this paper, we developed a single cell growth model with coarse-grained metabolic pathways including proteome allocation and thermodynamic constraints on the overflow pathway. The model can accurately capture the flux of thermodynamically controlled overflow pathway and growth rate of cells under different growth conditions. Moreover, when it is applied to study the cross-feeding, the model can reveal the short-term dynamics and long-term dynamics of cross-feeding stable polymorphism seen in experiments.