A Genome-Scale Insight into the Effect of Shear Stress During the Fed-Batch Production of Clavulanic Acid by .

Microorganisms

Grupo de Bioprocesos, Departamento de Ingeniería Química, Universidad de Antioquia (UdeA), Calle 70 No. 52-21, Medellín 050010, Colombia.

Published: August 2020


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Article Abstract

is a filamentous Gram-positive bacterial producer of the β-lactamase inhibitor clavulanic acid. Antibiotics biosynthesis in the genus is usually triggered by nutritional and environmental perturbations. In this work, a new genome scale metabolic network of 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569809PMC
http://dx.doi.org/10.3390/microorganisms8091255DOI Listing

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