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

## TL;DR

This paper explores how microbes might reduce their energy waste during faster growth by changing their metabolic strategies.

## Contribution

The paper introduces a general criterion to predict when energy waste per biomass decreases during metabolic shifts in microbes.

## Key findings

- Optimizing resource allocation can lead to metabolic pathways with lower driving force but higher flux.
- A general criterion is derived to predict when energy waste per biomass decreases during metabolic switches.
- Experiments are proposed to test if energy waste can decrease with faster microbial growth.

## Abstract

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.