Planta Med 2012; 78 - PI49
DOI: 10.1055/s-0032-1320736

Novel purification protocol for in vivo produced analogues of Amphotericin B

O Ibrahim 1, P Caffrey 2, B Rawlings 1
  • 1Department of Chemistry, University of Leicester. LE1 7RH
  • 2School of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland

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.

Fig.1: R=COOH Amphotericin B

Fig.2: R=Me 16-Descarboxyl-16-methyl-amphotericin B