TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus

Autor: Howard Ramirez-Malule, Víctor A. López-Agudelo, David Gómez-Ríos, Silvia Ochoa, Rigoberto Ríos-Estepa, Stefan Junne, Peter Neubauer
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Bioengineering, Vol 8, Iss 8, p 103 (2021)
Druh dokumentu: article
ISSN: 2306-5354
DOI: 10.3390/bioengineering8080103
Popis: Streptomyces clavuligerus (S. clavuligerus) has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of β-lactamase enzymes. In this study, S. clavuligerus cultivated in 2D rocking bioreactor in fed-batch operation produced CA at comparable rates to those observed in stirred tank bioreactors. A reduced model of S. clavuligerus metabolism was constructed by using a bottom-up approach and validated using experimental data. The reduced model was implemented for in silico studies of the metabolic scenarios arisen during the cultivations. Constraint-based analysis confirmed the interrelations between succinate, oxaloacetate, malate, pyruvate, and acetate accumulations at high CA synthesis rates in submerged cultures of S. clavuligerus. Further analysis using shadow prices provided a first view of the metabolites positive and negatively associated with the scenarios of low and high CA production.
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