PRODUCTION OF CLAVULANIC ACID BY FERMENTATION OF Streptomyces clavuligerus: EVALUATION OF DIFFERENT CULTURE MEDIA AND MATHEMATICAL MODELING

Clavulanic acid (CA) is a beta-lactam antibiotic exhibiting potent inhibitory capacity towards beta-lactamases. In this paper we assessed the production of CA in four culture media reported in the literature compared to a novel culture medium. The results of lab-scale bioreactor studies were used to establish the optimum glycerol concentration in the selected media. It was observed that the presence of complex media with a mixture of free amino acids, are suitable for the production of CA. Glycerol showed an optimum value compared to the production of CA in 50 g.L-1 and inhibitory effect was observed at concentrations of 100 g.L-1. With the complex medium and 50 g.L-1 of glycerol, the concentration of CA achieved was 994 mg.L-1. A mathematical model was proposed and their fit to the experimental results was evaluated. The proposed mathematical model includes a type Contois kinetics for biomass and product formation kinetics partially associated with growth, and showed a significant adjustment with 95% confidence level.