Inositol phosphorylceramide (IPC) synthase is a common and essential enzyme in fungi and plants, which catalyzes the transfer of phosphoinositol to the C-1 hydroxy of ceramide to produce IPC. This reaction is a key step in fungal sphingolipid biosynthesis, therefore the enzyme is a potential target for the development of nontoxic therapeutic antifungal agents. Natural products with a desired biological activity, aureobasidin A (AbA), khafrefungin, and galbonolide A, have been reported. AbA, a cyclic depsipeptide containing 8 amino acids and a hydroxyl acid, is a broad spectrum antifungal with strong activity against many pathogenic fungi such as Candida spp., Cryptococcus neoformans, and some Aspergillus spp. Khafrefungin, an aldonic acid ester with a C22 long alkyl chain, has antifungal activity against C. albicans, Cr. Neoformans, and Saccharomyces cerevisiae. Galbonolide A is a 14-membered macrolide with fungicidal activity against clinically important strains, and is especially potent against Cr. neoformans. These classes of natural products are potent and specific antifungal agents. We review current progress in the development of IPC synthase inhibitors with antifungal activities, and present structure-activity relationships (SAR), physicochemical and structural properties, and synthetic methodology for chemical modification.

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A novel actinomycete, strain KZ0017T, was isolated from a forest soil collected in Ohnuma, Fukushima, Japan. Strain KZ0017T formed spore chains borne on top of short sporophores arising from vegetative hyphae. Spores were non-motile and cylindrical with smooth surfaces. Strain KZ0017T contained meso-diaminopimelic (A2pm) acid, 3-OH A2pm, d-glutamic acid, glycine and l-alanine in the cell-wall peptidoglycan, and xylose, mannose, galactose, rhamnose and ribose in cell-wall hydrolysates. The acyl type of the cell-wall polysaccharides was glycolyl. The predominant menaquinones were MK-10(H4) and MK-10(H6); MK-10(H8) was a minor component. The polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylinositol and several unknown lipids and glycolipids. The major fatty acids were iso-C16 : 0, 10-methyl-C17 : 0 and iso-C17 : 1ω9c. The DNA G+C content was 70.7 mol%. The 16S rRNA gene sequence of the isolate formed a monophyletic cluster with the single member of the genus Longispora in the family Micromonosporaceae. On the basis of morphological, chemotaxonomic and phylogenetic properties, strain KZ0017T represents a novel species of the genus Longispora, for which the name Longispora fulva sp. nov. is proposed; the type strain is KZ0017T ( = NBRC 105670T = DSM 45356T).