Ramirez-Malule, HowardLópez-Agudelo, Víctor A.Gómez-Ríos, DavidOchoa, SilviaRíos-Estepa, RigobertoJunne, StefanNeubauer, Peter2021-08-172021-08-172021-07-22https://depositonce.tu-berlin.de/handle/11303/13512http://dx.doi.org/10.14279/depositonce-12295Streptomyces 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.en570 Biowissenschaften; BiologieStreptomyces clavuligerusclavulanic acidfed-batch cultivationTCA cycle intermediateflux balance analysissingle-use bioreactorshadow pricesArticle2021-08-012306-5354