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

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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.

Data availability

All data is available via the paper GitHub repository (https://github.com/cremerlab/flux_parity) and is registered in Zenodo via DOI: 10.5281/zenodo.5893799

The following data sets were generated

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Griffin Chure

Department of Biology, Stanford University, Stanford, United States

For correspondence
gchure@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2216-2057
Jonas Cremer

Department of Biology, Stanford University, Stanford, United States

For correspondence
jbcremer@stanford.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2328-5152

Funding

National Science Foundation (2010807)

Griffin Chure

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

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.