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

Overview

Journal Bioengineering (Basel)

Date 2021 Aug 26

PMID 34436106

Citations 2

Authors

Howard Ramirez-Malule

Victor A Lopez-Agudelo

David Gomez-Rios

Silvia Ochoa

Rigoberto Rios-Estepa

Stefan Junne

Peter Neubauer

Affiliations

Soon will be listed here.

Abstract

() has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of β-lactamase enzymes. In this study, 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 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 . 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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