Control of actinomycin D biosynthesis in Streptomyces parvullus: regulation of tryptophan oxygenase activity.
Tryptophan oxygenase (tryptophan 2,3-dioxygenase) activity increases immediately before the initiation of actinomycin D production by Streptomyces parvullus. We have attempted to discern whether this increase is due to a release from catabolite repression or to the synthesis of an inducer substance. The standard culture medium (glutamic acid-histidine-fructose medium) used in antibiotic production studies with S. parvullus contains l-glutamate as a major constituent. l-Glutamate is almost totally consumed before the onset of actinomycin D synthesis. The addition of 10 mM l-glutamate at this stage completely abolished actinomycin D production as well as tryptophan oxygenase synthesis. Fourteen amino acids were tested for a similar effect. Of these, l-glutamate and l-aspartate had the most dramatic effect on tryptophan oxygenase and beta-galactosidase (beta-d-galactosidase), another inducible enzyme. Standard glutamic acid-histidine-fructose medium, preincubated for 23 h to remove l-glutamate, allowed the synthesis of actinomycin D and tryptophan oxygenase by cells at a stage of growth normally considered too early for antibiotic production. A chemically defined medium lacking l-glutamate and adjusted to pH 8.0 was designed to simulate the preincubation medium. The transfer of cells to this artificial preincubation medium resulted in the appearance of tryptophan oxygenase as early as 19 h before normal synthesis occurred, eliminating the possibility that an inducer molecule is synthesized and excreted during the preincubation period. The results of these studies suggest that the increase in tryptophan oxygenase activity before the onset of actinomycin D synthesis, as well as the synthesis of actinomycin D itself, is due to a release from l-glutamate catabolite repression.
D000596:Amino Acids / Q000494:pharmacology; D002241:Carbohydrates / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D002701:Chloramphenicol / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D003609:Dactinomycin / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007700:Kinetics; D013302:Streptomyces / Q000378:metabolism*; D014366:Tryptophan Oxygenase / Q000096:biosynthesis*
D000596:Amino Acids; D002241:Carbohydrates; D002264:Carboxylic Acids; D005971:Glutamates; D003609:Dactinomycin; D018698:Glutamic Acid; D002701:Chloramphenicol; D000242:Cyclic AMP; D014366:Tryptophan Oxygenase; D006152:Cyclic GMP