Novel purification protocol for in vivo produced analogues of Amphotericin B

Amphotericin B (1), produced by Streptomyces nodosus, is a medically important antifungal that is also active against Leishmania parasites. However, its use is severely limited by its toxicity. Genetic disruption of one of the post PKS genes encoding a cytochrome P450 produces 2, which has been shown to be less toxic and retains antifungal activity. We report here improved production and purification protocols involving the intermediacy of a less polar Fmoc derivative. Development of this methodology will enable the production of gram quantities of these metabolites for extensive biological assays and assist with investigations into the mode of action of these antibiotics.