Background: Clavulanic acid is an important beta-lactamase inhibitor produced as a secondary metabolite by the
actinomycete
Streptomyces clavuligerus
. Clavulanic acid is chemically unstable; therefore, it is degraded during
bacterial cultivation. In this work, the adsorbents clinoptilolite, activated carbon, calcined hydrotalcite, and
Amberlite IRA 400 anionic exchange resin were studied in terms of their ability to adsorb clavulanic acid
during extractive fermentation, in order to prevent product degradation and avoid product concentrations
reaching inhibitory levels. Adsorption assays were used to investigate the effect of pH, and the decrease in the
clavulanic acid concentration in the culture broth was measured for each adsorbent.
Results: IRA 400 was found to bemost effective, with 78% adsorption of clavulanic acid. The maximum production
of clavulanic acid in Erlenmeyer flask cultures increased 86% in terms of mass of CA, and 248 % in cumulative CA
concentration, with the use of Amberlite IRA 400 as adsorbent in extractive fermentation, compared to control
fermentation performed without product removal.
Conclusions: The results indicated that extractive fermentation using a solid phase could be an important way of
enhancing clavulanic acid titers. It was also possible to show that clavulanic acid acts as an inhibitor of its own
synthesis.