Nitrogen repression of gilvocarcin V production in Streptomyces arenae 2064.
Analysis of gilvocarcin V production by Streptomyces arenae in complex and chemically defined media revealed strong nitrogen repression of antibiotic biosynthesis. Nitrogen regulation was first suggested by the observation of a 10-fold increase in gilvocarcin V production when the ammonium ion trapping agent Mg3(PO4)2.8H2O was added to complex medium. In a chemically defined medium, cell mass increased as the initial ammonium sulfate concentrations approached 7.5 mM; however, antibiotic production was strongly repressed at ammonium sulfate concentrations exceeding 1.5 mM. Repression of gilvocarcin V production at 7.5 mM ammonium sulfate was maximally reversed by adding Mg3(PO4)2.8H2O to the medium at 25 mM; specific antibiotic production attained a level 2.5-fold higher than at the nonrepressive ammonium salt concentration of 1.5 mM. Evaluation of the effects of soluble inorganic phosphate concentrations upon gilvocarcin V titers suggested that the relatively insoluble Mg3(PO4)2.8H2O must in fact serve as an ammonium ion-trapping agent, as previously reported in other fermentation systems, not as a supplementary source of phosphate for growth and antibiotic production. These studies also revealed a minor repression of antibiotic synthesis at elevated levels of soluble phosphate. Comparisons of several amino acids as nitrogen sources in a Mg3(PO4)2.8H2O-containing medium indicated that L-aspartic acid and glycine promoted the highest yields of gilvocarcin V. Metabolism of these two amino acids into precursors of the polyketide pathway for gilvocarcin V biosynthesis is postulated.
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D000596:Amino Acids / Q000378:metabolism; D000617:Aminoglycosides; D000645:Ammonium Sulfate / Q000494:pharmacology; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic / Q000096:biosynthesis*; D003374:Coumarins; D003470:Culture Media; D006027:Glycosides / Q000096:biosynthesis; D008274:Magnesium / Q000494:pharmacology; D017616:Magnesium Compounds; D009584:Nitrogen / Q000378:metabolism / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology; D013302:Streptomyces / Q000378:metabolism*
D000596:Amino Acids; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D003374:Coumarins; D003470:Culture Media; D006027:Glycosides; D017616:Magnesium Compounds; D010710:Phosphates; C030781:magnesium phosphate; C031781:gilvocarcin V; D008274:Magnesium; D009584:Nitrogen; D000645:Ammonium Sulfate