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 a-diketone and jS-ketoaldehyde functional groups. Australifungin exhibited broad spectrum antifungal activity against humanpathogenic fungi with MICs against Candida spp., Cryptococcus neoformans, and Aspergillus spp. between 0.01 5 and 1.0 //g/ml. Modeof action studies revealed that australifungin interfered with fungal lipid metabolism by specifically inhibiting sphingolipid synthesis at the step converting sphinganine to ceramide.

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Serine palmitoyltransferase condenses serine with a fatty acyl-CoA to form ketodihydrosphingosine in the first committed step of sphingolipid biosynthesis. A family of novel compounds, called the sphingofungins, have recently been discovered to be the first specific inhibitors of this enzyme1~3). Initially identified as antifungal agents, the sphingofungins resemble the long chain base intermediates in the sphingolipid pathway and inhibit the serine Liquid production medium C consisted of 10 g of beta-cyclodextrin, 40 g of dextrin, 7 g of distillers solubles and 5 g of yeast extract per liter of distilled water. Forty four ml of this mediumwas distributed into 250-ml unbaffled Erlenmeyer flasks. Production of antifungal activity was accomplished by adding 2ml of the seed culture described above to each production flask. Production cultures were incubated at 28°C for 4 days. Antifungal activity was produced in the culture filtrate and could conveniently be detected using the formation of zones of inhibition against Candida and Penicillium.Twoliters of the fermentation described above

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