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 $\beta-lactamase$ and penicillin-binding proteins. However, the degradation caused by these enzymes was not highly significant compared with the degradation during the cultivation, owing to irreversible reactions between CA and enzymes.

Keywords: Clavulanic acid degradation, β-lactamases, metabolites, penicillin-binding proteins (PBPs)