An analytical theory of balanced cellular growth.

Nature Communications
Hugo Dourado, Martin J. Lercher

Abstract

The biological fitness of microbes is largely determined by the rate with which they replicate their biomass composition. Mathematical models that maximize this balanced growth rate while accounting for mass conservation, reaction kinetics, and limits on dry mass per volume are inevitably non-linear. Here, we develop a general theory for such models, termed Growth Balance Analysis (GBA), which provides explicit expressions for protein concentrations, fluxes, and growth rates. These variables are functions of the concentrations of cellular components, for which we calculate marginal fitness costs and benefits that are related to metabolic control coefficients. At maximal growth rate, the net benefits of all concentrations are equal. Based solely on physicochemical constraints, GBA unveils fundamental quantitative principles of cellular resource allocation and growth; it accurately predicts the relationship between growth rates and ribosome concentrations in E. coli and yeast and between growth rate and dry mass density in E. coli.

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Citations

Jun 20, 2020·Genome Biology·Itai Yanai, Martin Lercher
Oct 18, 2020·Nature Communications·Xiao-Pan HuMartin J Lercher
May 26, 2021·Molecular Systems Biology·Matteo MoriChristina Ludwig
Jul 20, 2021·PLoS Computational Biology·Laurens H J Krah, Rutger Hermsen
Aug 4, 2021·Proceedings of the National Academy of Sciences of the United States of America·Enno R OldewurtelSven van Teeffelen
Oct 27, 2021·PLoS Biology·Hugo DouradoMartin J Lercher

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Methods Mentioned

BETA
protein folding

Software Mentioned

CAFBA
GetData Graph Digitizer
ME
GBA
BRENDA
gnu R

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