THE DISCOVERY OF AUSTRALIFUNGIN, A NOVEL INHIBITOR OF SPHINGANINE N-ACYLTRANSFERASE FROM SPORORMIELLA-AUSTRALIS - PRODUCING ORGANISM, FERMENTATION, ISOLATION, AND BIOLOGICAL-ACTIVITY

Potent antifungal activity was detected in fermentation extracts of Sporormiella australis and two related components were isolated from solid fermentations using silica gel and high speed countercurrent chromatography. The most active antifungal component, australifungin, contained a unique combination of alpha-diketone and beta-ketoaldehyde functional groups. Australifungin exhibited broad spectrum antifungal activity against human pathogenic fungi with MICs against Candida spp., Cryptococcus neoformans, and Aspergillus spp, between 0.015 and 1.0 mu g/ml. Mode of action studies revealed that australifungin interfered with fungal lipid metabolism by specifically inhibiting sphingolipid synthesis at the step converting sphinganine to ceramide.