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 muCi/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 approximately 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.
D000085:Acetates / Q000378:metabolism; D000438:Alcohols / Q000494:pharmacology; D000666:Amphotericin B / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000138:chemical synthesis; D003864:Depression, Chemical; D004952:Esters / Q000138:chemical synthesis; D005285:Fermentation; D013302:Streptomyces / Q000187:drug effects / Q000378:metabolism
D000085:Acetates; D000438:Alcohols; D004952:Esters; D003840:Deoxycholic Acid; D000666:Amphotericin B