Computation of condition-dependent proteome allocation reveals variability in the macro and micro nutrient requirements for growth

Abstract Sustaining a robust metabolic network requires a balanced and fully functioning proteome. In addition to amino acids, many enzymes require cofactors (coenzymes and engrafted prosthetic groups) to function properly. Extensively validated genome-scale models of metabolism and gene expression (ME-models) have the unique ability to compute an optimal proteome composition underlying a metabolic phenotype, including the provision of all required cofactors. Here we use the ME-model for Escherichia coli K-12 MG1655 to computationally examine how environmental conditions change the proteome and its accompanying cofactor usage. We found that: (1) The cofactor requirements computed by the ME model mostly agree with the standard biomass objective function used in models of metabolism alone (M models); (2) ME-model computations reveal non-intuitive variability in cofactor use under different growth conditions; (3) An analysis of ME-model predicted protein use in aerobic and anaerobic conditions suggests an enrichment in the use of prebiotic amino acids in the proteins used to sustain anaerobic growth (4) The ME-model could describe how limitation in key protein components affect the metabolic state of E. coli. Genome-scale models have thus reached a level of sophistication where they reveal intricate properties of functional proteomes and how they support different E. coli lifestyles..

Medienart:

Preprint

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

bioRxiv.org - (2021) vom: 15. Dez. Zur Gesamtaufnahme - year:2021

Sprache:

Englisch

Beteiligte Personen:

Lloyd, Colton J. [VerfasserIn]
Monk, Jonathan [VerfasserIn]
Yang, Laurence [VerfasserIn]
Ebrahim, Ali [VerfasserIn]
Palsson, Bernhard O. [VerfasserIn]

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doi:

10.1101/2020.03.23.003236

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI000816388