TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus
| dc.contributor.author | Ramirez-Malule, Howard | |
| dc.contributor.author | López-Agudelo, Víctor A. | |
| dc.contributor.author | Gómez-Ríos, David | |
| dc.contributor.author | Ochoa, Silvia | |
| dc.contributor.author | Ríos-Estepa, Rigoberto | |
| dc.contributor.author | Junne, Stefan | |
| dc.contributor.author | Neubauer, Peter | |
| dc.date.accessioned | 2021-08-17T11:25:48Z | |
| dc.date.available | 2021-08-17T11:25:48Z | |
| dc.date.issued | 2021-07-22 | |
| dc.date.updated | 2021-08-01T18:38:12Z | |
| dc.description.abstract | 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. | en |
| dc.description.sponsorship | BMBF, 01DN19005, Bioreaktoren für Scaling Up und Down: Schnellere Bioprozessentwicklung und Implementierung in ländlichen und städtischen Regionen | en |
| dc.identifier.eissn | 2306-5354 | |
| dc.identifier.uri | https://depositonce.tu-berlin.de/handle/11303/13512 | |
| dc.identifier.uri | http://dx.doi.org/10.14279/depositonce-12295 | |
| dc.language.iso | en | en |
| dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject.ddc | 570 Biowissenschaften; Biologie | de |
| dc.subject.other | Streptomyces clavuligerus | en |
| dc.subject.other | clavulanic acid | en |
| dc.subject.other | fed-batch cultivation | en |
| dc.subject.other | TCA cycle intermediate | en |
| dc.subject.other | flux balance analysis | en |
| dc.subject.other | single-use bioreactor | en |
| dc.subject.other | shadow prices | en |
| dc.title | TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus | en |
| dc.type | Article | en |
| dc.type.version | publishedVersion | en |
| dcterms.bibliographicCitation.articlenumber | 103 | en |
| dcterms.bibliographicCitation.doi | 10.3390/bioengineering8080103 | en |
| dcterms.bibliographicCitation.issue | 8 | en |
| dcterms.bibliographicCitation.journaltitle | Bioengineering | en |
| dcterms.bibliographicCitation.originalpublishername | MDPI | en |
| dcterms.bibliographicCitation.originalpublisherplace | Basel | en |
| dcterms.bibliographicCitation.volume | 8 | en |
| tub.accessrights.dnb | free | en |
| tub.affiliation | Fak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Bioverfahrenstechnik | de |
| tub.affiliation.faculty | Fak. 3 Prozesswissenschaften | de |
| tub.affiliation.group | FG Bioverfahrenstechnik | de |
| tub.affiliation.institute | Inst. Biotechnologie | de |
| tub.publisher.universityorinstitution | Technische Universität Berlin | en |