TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus
| Autor: | Rigoberto Ríos-Estepa, Stefan Junne, Silvia Ochoa, Peter Neubauer, Howard Ramírez-Malule, David Gómez-Ríos, Víctor A. López-Agudelo |
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| Rok vydání: | 2021 |
| Předmět: |
Technology
QH301-705.5 fed-batch cultivation single-use bioreactor flux balance analysis Streptomyces clavuligerus Bioengineering Article 03 medical and health sciences clavulanic acid TCA cycle intermediate shadow prices ddc:570 Bioreactor Citrate synthase Biology (General) 030304 developmental biology chemistry.chemical_classification 0303 health sciences biology 030306 microbiology Chemistry Metabolism biology.organism_classification Single-use bioreactor Flux balance analysis Citric acid cycle Enzyme Biochemistry biology.protein |
| Zdroj: | Bioengineering; Volume 8; Issue 8; Pages: 103 Bioengineering Bioengineering, Vol 8, Iss 103, p 103 (2021) |
| 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. |
| Databáze: | OpenAIRE |
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