Enhancing genome-scale metabolic models with kinetic data: resolving growth and citramalate production trade-offs in <i>Escherichia coli</i>

Lázaro, Jorge (Universidad de Zaragoza) ; Wongprommoon, Arin ; Júlvez, Jorge (Universidad de Zaragoza) ; Oliver, Stephen G

Resumen: Metabolic models are valuable tools for analyzing and predicting cellular features such as growth, gene essentiality, and product formation. Among the various types of metabolic models, two prominent categories are constraint-based models and kinetic models. Constraint-based models typically represent a large subset of an organism’s metabolic reactions and incorporate reaction stoichiometry, gene regulation, and constant flux bounds. However, their analyses are restricted to steady-state conditions, making it difficult to optimize competing objective functions. In contrast, kinetic models offer detailed kinetic information but are limited to a smaller subset of metabolic reactions, providing precise predictions for only a fraction of an organism’s metabolism. To address these limitations, we proposed a hybrid approach that integrates these modeling frameworks by redefining the flux bounds in genome-scale constraint-based models using kinetic data. We applied this method to the constraint-based model of Escherichia coli, examining both its wild-type form and a genetically modified strain engineered for citramalate production. Our results demonstrate that the enriched model achieves more realistic reaction flux boundaries. Furthermore, by fixing the growth rate to a value derived from kinetic information, we resolved a flux bifurcation between growth and citramalate production in the modified strain, enabling accurate predictions of citramalate production rates.

Idioma: Inglés

DOI: 10.1093/bioadv/vbaf166

Año: 2025

Publicado en: Bioinformatics advances 5, 1 (2025), [11 p]
ISSN: 2635-0041

Financiación: info:eu-repo/grantAgreement/EUR/AEI/TED2021-130449B-I00
Financiación: info:eu-repo/grantAgreement/ES/DGA/T21-23R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2020-113969RB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Lenguajes y Sistemas Inf. (Dpto. Informát.Ingenie.Sistms.)