An optimal regulation of fluxes dictates microbial growth in and out of steady state

Elife. 2023 Mar 10:12:e84878. doi: 10.7554/eLife.84878.

Abstract

Effective coordination of cellular processes is critical to ensure the competitive growth of microbial organisms. Pivotal to this coordination is the appropriate partitioning of cellular resources between protein synthesis via translation and the metabolism needed to sustain it. Here, we extend a low-dimensional allocation model to describe the dynamic regulation of this resource partitioning. At the core of this regulation is the optimal coordination of metabolic and translational fluxes, mechanistically achieved via the perception of charged- and uncharged-tRNA turnover. An extensive comparison with ≈ 60 data sets from Escherichia coli establishes this regulatory mechanism's biological veracity and demonstrates that a remarkably wide range of growth phenomena in and out of steady state can be predicted with quantitative accuracy. This predictive power, achieved with only a few biological parameters, cements the preeminent importance of optimal flux regulation across conditions and establishes low-dimensional allocation models as an ideal physiological framework to interrogate the dynamics of growth, competition, and adaptation in complex and ever-changing environments.

Keywords: E. coli; S. cerevisiae; cell biology; infectious disease; microbial physiology; microbiology; physics of living systems; physiological modeling; resource allocation; systems biology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Physiological Phenomena
  • Escherichia coli* / metabolism
  • Models, Biological*

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.