PRODUCTION OF AMPHOTERICIN B-¹⁴C BY STREPTOMYCES NODOSUS FERMENTATION, AND PREPARATION OF THE AMPHOTERICIN B-¹⁴C-METHYL-ESTER

Abstract

A selected strain of Streptomyces nodosus capable of producing 4, 500μg amphotericin B per ml in a complex medium was able to produce 3, 500μg amphotericin B per ml in defined medium. Amphotericin A was coproduced in both fermentation media. An improved method was developed for their quantitative determination directly from the culture broth, and a satisfactory isolation procedure for amphotericins A and B was worked out. Final separation of the two compounds was accomplished by countercurrent distribution. Several ¹⁴C-precursors were used to optimize the specific activity of amphotericin B, and depending on the time of addition to the inoculated medium and the precursor concentration, different rates of incorporation were obtained. Amphotericin B-¹⁴C-methyl-ester was synthesized by chemical conversion of purified amphotericin B with freshly prepared ¹⁴C-diazomethane.