The mechanism for the methionine mediated reduction of anthramycin yields in Streptomyces refuineus fermentations

The addition of L-methionine to cultures of Streptomyces refuineus producing anthramycin, results in an apparent decrease in the antibiotic titer. It has been shown that this effect is not due to the inhibition of tyrosinase, an enzyme implicated in anthramycin biosynthesis. The inhibitory effect also appears unlikely to be due to a regulatory role played by methionine in a non-precursor fashion. Experiments with radiolabeled anthramycin have revealed that the reduced yields of the antibiotic are due to the interaction of anthramycin with generated reactive metabolites produced in the methionine-supplemented cultures.