Title
Elementary vectors and autocatalytic sets for resource allocation in next-generation models of cellular growth
Abstract
Traditional (genome-scale) metabolic models of cellular growth involve an approximate biomass “reaction”, which specifies biomass composition in terms of precursor metabolites (such as amino acids and nucleotides). On the one hand, biomass composition is often not known exactly and may vary drastically between conditions and strains. On the other hand, the predictions of computational models crucially depend on biomass. Also elementary flux modes (EFMs), which generate the flux cone, depend on the biomass reaction. To better understand cellular phenotypes across growth conditions, we introduce and analyze new classes of elementary vectors for comprehensive (next-generation) metabolic models, involving explicit synthesis reactions for all macromolecules. Elementary growth modes (EGMs) are given by stoichiometry and generate the growth cone. Unlike EFMs, they are not support-minimal, in general, but cannot be decomposed “without cancellations”. In models with additional (capacity) constraints, elementary growth vectors (EGVs) generate a growth polyhedron and depend also on growth rate. However, EGMs/EGVs do not depend on the biomass composition. In fact, they cover all possible biomass compositions and can be seen as unbiased versions of elementary flux modes/vectors (EFMs/EFVs) used in traditional models. To relate the new concepts to other branches of theory, we consider autocatalytic sets of reactions. Further, we illustrate our results in a small model of a self-fabricating cell, involving glucose and ammonium uptake, amino acid and lipid synthesis, and the expression of all enzymes and the ribosome itself. In particular, we study the variation of biomass composition as a function of growth rate. In agreement with experimental data, low nitrogen uptake correlates with high carbon (lipid) storage.
Keywords
RibosomesStoichiometryLipidsEnzyme metabolismEnzymesGlucoseChemical synthesisEnzyme kinetics
Object type
Language
English [eng]
Persistent identifier
https://phaidra.univie.ac.at/o:1655516
Appeared in
Title
PLOS Computational Biology
Volume
18
Issue
2
ISSN
1553-7358
Issued
2022
Publisher
Public Library of Science (PLoS)
Date issued
2022
Access rights
Rights statement
© 2022 Müller et al

Download

University of Vienna | Universitätsring 1 | 1010 Vienna | T +43-1-4277-0