Local flux coordination and global gene expression regulation in metabolic modeling.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
14 09 2023
14 09 2023
Historique:
received:
05
11
2020
accepted:
04
09
2023
medline:
18
9
2023
pubmed:
15
9
2023
entrez:
14
9
2023
Statut:
epublish
Résumé
Genome-scale metabolic networks (GSMs) are fundamental systems biology representations of a cell's entire set of stoichiometrically balanced reactions. However, such static GSMs do not incorporate the functional organization of metabolic genes and their dynamic regulation (e.g., operons and regulons). Specifically, there are numerous topologically coupled local reactions through which fluxes are coordinated; the global growth state often dynamically regulates many gene expression of metabolic reactions via global transcription factor regulators. Here, we develop a GSM reconstruction method, Decrem, by integrating locally coupled reactions and global transcriptional regulation of metabolism by cell state. Decrem produces predictions of flux and growth rates, which are highly correlated with those experimentally measured in both wild-type and mutants of three model microorganisms Escherichia coli, Saccharomyces cerevisiae, and Bacillus subtilis under various conditions. More importantly, Decrem can also explain the observed growth rates by capturing the experimentally measured flux changes between wild-types and mutants. Overall, by identifying and incorporating locally organized and regulated functional modules into GSMs, Decrem achieves accurate predictions of phenotypes and has broad applications in bioengineering, synthetic biology, and microbial pathology.
Identifiants
pubmed: 37709734
doi: 10.1038/s41467-023-41392-6
pii: 10.1038/s41467-023-41392-6
pmc: PMC10502109
doi:
Substances chimiques
O-(glucuronic acid 2-sulfate)-(1--4)-O-(2,5)-anhydromannitol 6-sulfate
98632-68-9
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5700Informations de copyright
© 2023. Springer Nature Limited.
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