A coarse-grained resource allocation model of carbon and nitrogen metabolism in unicellular microbes
Author(s)
Kleijn, Istvan T
Marguerat, Samuel
Shahrezaei, Vahid
Type
Journal Article
Abstract
Coarse-grained resource allocation models (C-GRAMs) are simple mathematical models of cell physiology, where large components of the macromolecular composition are abstracted into single entities. The dynamics and steady-state behaviour of such models provides insights on optimal allocation of cellular resources and have explained experimentally observed cellular growth laws, but current models do not account for the uptake of compound sources of carbon and nitrogen. Here, we formulate a C-GRAM with nitrogen and carbon pathways converging on biomass production, with parametrizations accounting for respirofermentative and purely respiratory growth. The model describes the effects of the uptake of sugars, ammonium and/or compound nutrients such as amino acids on the translational resource allocation towards proteome sectors that maximized the growth rate. It robustly recovers cellular growth laws including the Monod law and the ribosomal growth law. Furthermore, we show how the growth-maximizing balance between carbon uptake, recycling, and excretion depends on the nutrient environment. Lastly, we find a robust linear correlation between the ribosome fraction and the abundance of amino acid equivalents in the optimal cell, which supports the view that simple regulation of translational gene expression can enable cells to achieve an approximately optimal growth state.
Date Issued
2023-09
Date Acceptance
2023-09-08
Citation
Journal of the Royal Society Interface, 2023, 20 (206)
ISSN
1742-5662
Publisher
The Royal Society
Journal / Book Title
Journal of the Royal Society Interface
Volume
20
Issue
206
Copyright Statement
© 2023 The Authors.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/37751876
Subjects
cellular growth laws
gene expression
mathematical modelling
metabolism
microbial growth
proteome allocation
Publication Status
Published
Coverage Spatial
England
Article Number
20230206
Date Publish Online
2023-09-29