Regulation of tyrosine biosynthesis by phenylalanine in anthramycin-producing Streptomyces refuineus.

The regulation of tyrosine production in the anthramycin-producing organism Streptomyces refuineus var.thermotolerans has been studied with wild-type and tyrosine auxotrophic organisms.Growth of the auxotroph on minimal medium plus phenylalanine suggested that phenylalanine may increase the supply of tyrosine.In incubation with whole cells, tyrosine levels increased in response to added phenylalanine.However, no radiolabeled tyrosine was detected after incubation with 14C-phenylalanine.Thus, no phenylalanine hydroxylase is present.Phenylalanine was found to feedback inhibit prephenate dehydratase, resulting in an increase in NAD-dependent prephenate dehydrogenase activity, thus channeling prephenic acid toward tyrosine.Anthramycin is a pyrollo (1,4)benzodiazepine antitumor antibiotic produced by Streptomyces refuineus var.thermotolerans (NRRL 3143)1).HURLEY and coworkers have found that anthramycin is derived from tryptophan, tyrosine, and methionine2).As part of a study of the control mechanisms regulating anthramycin production, we are examining the control of biosynthesis of the aromatic amino acid precursors.Tyrosine auxotrophic mutants were created and one such mutant was found to grow on phenylalanine-supplemented minimal medium, although not as well as on tyrosine-supplemented