Biological properties and mode of action of clavams

The clavams valclavam and hydroxyethylclavam were both bacteriostatic and fungistatic. The molecular basis for growth inhibition of Escherichia coli was a non-competitive inhibition of homoserine-O-succinyltransferase (EC 2.3.1.46), thus blocking methionine biosynthesis. Eucaryotes such as Saccharomyces cerevisiae were inhibited by a different mode of action. Instead of interfering with methionine biosynthesis, the clavams inhibited the formation of RNA in living cells, although the RNA-polymerases of isolated yeast nuclei were not inhibited. The action of valclavam on E. coli was dependent on functional peptide transport systems.