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.