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

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Escuela de Ingeniería Química, Universidad del Valle, Cali 25360, Colombia
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Grupo de Investigación en Simulación, Diseño, Control y Optimización de Procesos (SIDCOP), Departamento de Ingeniería Química, Universidad de Antioquia UdeA, Medellín 050010, Colombia
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Escuela de Biociencias, Universidad Nacional de Colombia sede Medellín, Medellín 050010, Colombia
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Chair of Bioprocess Engineering, Institute of Biotechnology, Technische Universität Berlin, D-13355 Berlin, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Peter Neubauer, Christoph Herwig and Cornelia Kasper
Bioengineering 2021, 8(8), 103; https://doi.org/10.3390/bioengineering8080103
Received: 1 May 2021 / Revised: 4 July 2021 / Accepted: 16 July 2021 / Published: 22 July 2021
(This article belongs to the Special Issue Strategies for the Efficient Development of Microbial Bioprocesses)
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. View Full-Text
Keywords: Streptomyces clavuligerus; clavulanic acid; fed-batch cultivation; TCA cycle intermediate; flux balance analysis; single-use bioreactor; shadow prices Streptomyces clavuligerus; clavulanic acid; fed-batch cultivation; TCA cycle intermediate; flux balance analysis; single-use bioreactor; shadow prices
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MDPI and ACS Style

Ramirez-Malule, H.; López-Agudelo, V.A.; Gómez-Ríos, D.; Ochoa, S.; Ríos-Estepa, R.; Junne, S.; Neubauer, P. TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus. Bioengineering 2021, 8, 103. https://doi.org/10.3390/bioengineering8080103

AMA Style

Ramirez-Malule H, López-Agudelo VA, Gómez-Ríos D, Ochoa S, Ríos-Estepa R, Junne S, Neubauer P. TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus. Bioengineering. 2021; 8(8):103. https://doi.org/10.3390/bioengineering8080103

Chicago/Turabian Style

Ramirez-Malule, Howard, Víctor A. López-Agudelo, David Gómez-Ríos, Silvia Ochoa, Rigoberto Ríos-Estepa, Stefan Junne, and Peter Neubauer. 2021. "TCA Cycle and Its Relationship with Clavulanic Acid Production: A Further Interpretation by Using a Reduced Genome-Scale Metabolic Model of Streptomyces clavuligerus" Bioengineering 8, no. 8: 103. https://doi.org/10.3390/bioengineering8080103

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