Indole methylation protects diketopiperazine configuration in the maremycin biosynthetic pathway

The maremycin biosynthetic gene cluster has been identified in Streptomyces sp. B9173. Comparative metabolic profiling with knockout mutant strains led to the identification of new products correlated to the maremycin biosynthesis, in particular the “demethyl”-maremycins with an unexpected D-tryptophan unit. A biosynthetic pathway for the maremycins is proposed and plausible reasoning for tryptophan epimerization in the demethylmaremycin biosynthesis is also provided.