Degradation of Clavulanic Acid During the Cultivation of Streptomyces clavuligerus; Instability of Clavulanic Acid by Metabolites and Proteins from the Strain

Clavulanic acid (CA) produced by Streptomyces clavuligerus is degraded during the bacterial cultivation. The degradation was examined in three different aspects, including physical, chemical, and enzymatic effects, in order to understand the degradation during the cultivation. The result showed that CA was unstable in the production medium containing ammonium salts and amino acids, owing to ammonium ions and amine groups. In addition, the degradation was not only due to instability of CA by metabolites and proteins, but also enzymes from S. clavuligerus such as β-lactamase and penicillin-binding proteins.