A genome-scale insight into the effect of shear stress during the fed-batch production of clavulanic acid by streptomyces clavuligerus

Streptomyces clavuligerusis a filamentous Gram-positive bacterial producer of theβ-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the Streptomyces genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of Streptomyces clavuligerus was reconstructed and used to study the experimentally observed effect of oxygen and phosphate concentrations on clavulanic acid biosynthesis under high and low shear stress. A flux balance analysis based on experimental evidence revealed that clavulanic acid biosynthetic reaction fluxes are favored in conditions of phosphate limitation, and this is correlated with enhanced activity of central and amino acid metabolism, as well as with enhanced oxygen uptake. In silico and experimental results show a possible slowing down of tricarboxylic acid (TCA) due to reduced oxygen availability in low shear stress conditions. In contrast, high shear stress conditions are connected with high intracellular oxygen availability favoring TCA activity, precursors availability and clavulanic acid (CA) production.

• Autores: Ríos Estepa, Rigoberto; Gómez Ríos, David Andrés; López Agudelo, Victor Alonso; Ramírez Malule, Howard Diego; Neubauer, Peter; Junne, Stefan; Ochoa Cáceres, Silvia
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2020
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/46005
• Acceso en línea: https://hdl.handle.net/10495/46005
• Palabra clave: Streptomyces; Ácido Clavulánico; Clavulanic Acid; Metabolismo Secundario; Secondary Metabolism; Antibacterianos; Anti-Bacterial Agents; Inhibidores de beta - Lactamasas; Beta-Lactamase Inhibitors; Ácidos Tricarboxílicos; Tricarboxylic Acids; https://id.nlm.nih.gov/mesh/D013302; https://id.nlm.nih.gov/mesh/D019818; https://id.nlm.nih.gov/mesh/D064210; https://id.nlm.nih.gov/mesh/D000900; https://id.nlm.nih.gov/mesh/D065093; https://id.nlm.nih.gov/mesh/D014233; ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades; ODS 9: Industria, innovación e infraestructura. Construir infraestructuras resilientes, promover la industrialización inclusiva y sostenible y fomentar la innovación; ODS 12: Producción y consumo responsables. Garantizar modalidades de consumo y producción sostenibles
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/4.0/