EFFECT OF NITROGEN-SOURCE ON BIOSYNTHESIS OF RAPAMYCIN BY STREPTOMYCES-HYGROSCOPICUS

Six non-amino acid nitrogen compounds were examined as nitrogen source for growth of Streptomyces hygroscopicus and biosynthesis of rapamyci n. Of the nitrogen sources studied, ammonium sulfate was the best with respect to formation of rapamycin, and supported cell growth comparab le to the organic nitrogen sources used in the control chemically defi ned medium, ie, aspartate, arginine plus histidine. In the new chemica lly defined medium, which is buffered with 200 mM 2-(N-morpholino)etha nesulfonic acid to prevent decline of pH during fermentation, an ammon ium sulfate concentration of 40 mM was optimal for biosynthesis of rap amycin. Rapamycin production increased by more than 30% on both volume tric and specific bases as compared to the previous medium containing the three amino acids as nitrogen source.