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

Maarten J Droste1,2, Maaike Remeijer2, Robert Planqué1

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Microbial cells may decrease their entropy production rate (EPR) per unit biomass by shifting to a metabolism with lower thermodynamic driving force, even at faster growth rates.

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Area of Science:

  • Metabolic Engineering
  • Biophysics
  • Systems Biology

Background:

  • Thermodynamics links entropy production rate (EPR) to reaction rates in steady-state systems.
  • Living cells regulate metabolic activities by altering enzyme concentrations, influencing reaction rates.
  • Cells can potentially decouple EPR from reaction rates by optimizing metabolic pathways.

Purpose of the Study:

  • To investigate if microbial cells can reduce their EPR per unit biomass while increasing growth rate.
  • To explore the relationship between metabolic shifts, thermodynamic driving force, and EPR in microbial growth.
  • To develop criteria for predicting EPR changes during metabolic transitions.

Main Methods:

  • Analysis of a model metabolic network to demonstrate pathway selection based on resource allocation and driving force.
  • Modeling of yeast (Saccharomyces cerevisiae) chemostat cultivation using experimental data to study EPR per unit biomass.
  • Derivation of a general criterion to predict specific EPR changes after metabolic switches.

Main Results:

  • Optimal resource allocation can favor pathways with lower thermodynamic driving force but higher flux due to increased enzyme concentrations.
  • Current experimental data for Saccharomyces cerevisiae is insufficient to definitively conclude on EPR changes with growth rate.
  • A general criterion was derived to predict when specific EPR decreases after a metabolic switch.

Conclusions:

  • Microbial cells may achieve higher metabolic flux by utilizing pathways with reduced thermodynamic driving force, compensated by higher enzyme concentrations.
  • Further experiments are needed to confirm if specific EPR can decrease with increasing microbial growth rate.
  • The study provides a framework and criteria for future experimental investigations into microbial metabolic regulation and thermodynamics.