MICROBIAL PRODUCTION OF AMPHOTERICIN B-3H AND THE SYNTHESIS OF ITS SODIUM DESOXYCHOLATE (CARBOXYL-14C) COMPLEX AND METHYL-14C-ESTER

Amphotericin B-3H with a specific radioactivity in excess of 4 μCi/mg was produced by fermentation of Streptomyces nodosus IMRU 3694 in a complex medium, using acetate-3H as a precursor. The medium employed gave a production yield of 2.5-3.5 mg/ml of amphotericin B. The most efficient incorporation of acetate-3H occurred when the precursor was added at 24 hours after inoculation. It was observed, that the amount of amphotericin A co-produced in the fermentation broth with amphotericin B was significantly reduced by the addition of ethanol to the production medium. Complete inhibition of amphotericin A production was achieved at a level of 2% ethanol in the fermentation medium without an appreciable effect on the yield of amphotericin B. Methanol, 1-propanol, 2-propanol and 1-butanol lowered the yield of both antibiotics indiscriminately. The syntheses of amphotericin B-3H-Na desoxycholate (carboxyl-14C) complex and amphotericin B-3H methyl 14C-ester are also described.