A Trade-off between Force and Flow May Lead to Reduced Entropy Production Rate during Faster Microbial Growth.

Thermodynamics dictates that the entropy production rate (EPR) of a steady-state isothermal chemical reaction network rises with reaction rates. Living cells can, in addition, alter reaction rates by changing enzyme concentrations, giving them control over metabolic activities. Here, we ask whether microbial cells can break this relation between EPR and reaction rates by shifting to a metabolism with lower thermodynamic driving force (per unit of biomass) at faster growth. First, we study an example metabolic network to illustrate that maximization of metabolic flux by optimal allocation of resources can indeed lead to selection of a pathway with a lower driving force. This pathway then compensates for the reduction in driving force by relying on fewer enzymes with sufficiently increased concentrations, resulting in a higher flux. Next, we investigate the EPR per unit biomass of microbes that change their catabolic network as a function of their growth rate, using three models for chemostat cultivation of the yeast Saccharomyces cerevisiae that are calibrated with experimental data. Although current experimental evidence proved insufficient to give conclusive results, we derive a general criterion to predict when the specific EPR drops after a metabolic switch. We describe the experiments that are required to show that the specific EPR of a microbe can decrease with its growth rate.