Yasuyuki Takamatsu

Pleofungins, Novel Inositol Phosphorylceramide Synthase Inhibitors, from Phoma sp. SANK 13899 : I. Taxonomy, Fermentation, Isolation, and Biological Activities

In the course of a screening for inositol phosphorylceramide (IPC) synthase inhibitors, the novel inhibitors pleofungins A, B, C, and D were found in a mycelial extract of a fungus, Phoma sp. SANK13899. Purification was performed by 50% methanol and ethyl acetate extraction, reversed phase open-column chromatography, and HPLC separations. Pleofungin A inhibited the IPC synthase of Saccharomyces cerevisiae and Aspergillus fumigatus at IC50 values of 16 and 1.0 ng/ml, respectively. The inhibitor also suppressed the growth of Candida albicans, Cryptococcus neoformans, and A. fumigatus at MIC values of 2.0, 0.3, and 0.5 μg/ml, respectively. These biological properties indicate that pleofungins belong to a novel class of IPC synthase inhibitors efficacious against A. fumigatus.

Studies on novel bacterial translocase I inhibitors, A-500359s. V. Enhanced production of capuramycin and A-500359 A in Streptomyces griseus SANK 60196.

Streptomyces griseus SANK 60196 produces the novel nucleoside antibiotics A-500359 A, C, D and capuramycin. Enhanced production of capuramycin and A-500359 A was achieved through a number of medium modifications and a series of single colony isolations. The addition of maltose instead of glucose as the carbon source in a primary medium resulted in a 20-fold increase in the productivity of capuramycin. Furthermore, the addition of cobalt chloride (CoCl2) and yeast extract to the medium containing maltose drastically altered the production ratio of A-500359 A to capuramycin. Thus, the yield of A-500359 A increased up to 600 μg/ml in an optimal medium, while the yield in the primary medium was 1 μg/ml.

Zaragozic acids production from discomycetes

In search for new zaragozic acids and their derivatives that are potent inhibitors of squalene synthase, discomycetes of the order Leotiales were cultured and their fermentation broth was assayed. Three strains in 2 unidentified species ofMollisia were found to produce zaragozic acid D3 and three new analogs (F-10863s). Fermentative production, productivity of F-10863s and mycological characteristics of the producers are described. Discomycetes are expected to be a biological resource providing novel bioactive compounds.