Tca Cycle And Its Relationship With Clavulanic Acid Production: A Further Interpretation By Using A Reduced Genome-Scale Metabolic Model Of Streptomyces Clavuligerus
BIOENGINEERING-BASEL(2021)
摘要
Streptomyces clavuligerus (S. clavuligerus) has been widely studied for its ability to produce clavulanic acid (CA), a potent inhibitor of beta-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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关键词
Streptomyces clavuligerus, clavulanic acid, fed-batch cultivation, TCA cycle intermediate, flux balance analysis, single-use bioreactor, shadow prices
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