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A coarse-grained resource allocation model of carbon and nitrogen metabolism in unicellular microbes

Title: A coarse-grained resource allocation model of carbon and nitrogen metabolism in unicellular microbes
Authors: Kleijn, IT
Marguerat, S
Shahrezaei, V
Item 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.
Issue Date: Sep-2023
Date of Acceptance: 8-Sep-2023
URI: http://hdl.handle.net/10044/1/107091
DOI: 10.1098/rsif.2023.0206
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.
Publication Status: Published
Conference Place: England
Article Number: 20230206
Online Publication Date: 2023-09-29
Appears in Collections:Applied Mathematics and Mathematical Physics
Mathematics



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