Muraminomicins, new lipo-nucleoside antibiotics from Streptosporangium sp. SANK 60501-structure elucidations of muraminomicins and supply of the core component for derivatization.

We screened for bacterial phospho-N-acetylmuramyl-pentapeptide-translocase (MraY: EC 2.7.8.13) inhibitors with the aim of discovering novel antibiotics and observed inhibitory activity in the culture broth of an actinomycete, SANK 60501. The active compounds, muraminomicins A, B, C, D, E1, E2, F, G, H, and I exhibited strong inhibitory activity against MraY with IC50 values of 0.0105, 0.0068, 0.0104, 0.0099, 0.0115, 0.0109, 0.0089, 0.0134, 0.0186, and 0.0094 µg ml-1, respectively. Although muraminomicin F exhibited favorable antibacterial activity against drug-resistant Gram-positive bacteria, this activity was reduced with the addition of serum. To efficiently supply the core component for chemical modification studies, production was carried out in a controlled trial by adding myristic acid to the medium, and a purification method suitable for large-scale production was successfully developed.

Sterenin A, B, C and D, novel 11beta-hydroxysteroid dehydrogenase type 1 inhibitors from Stereum sp. SANK 21205.

The novel 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors known as sterenin A, B, C and D were found in a solid-state culture of the producing basidiomycetes identified as Stereum sp. SANK 21205. Purification of the 50% aq Me(2)CO extract of the culture was performed by EtOAc extraction, reversed phase open-column chromatography and successive ODS HPLC preparation. These compounds, whose structures were determined by several spectroscopic methods, were found to be novel isoindolinone alkaloids which exhibited potent selective inhibitory activities against 11beta-HSD1.

Colletoic acid, a novel 11beta-hydroxysteroid dehydrogenase type 1 inhibitor from Colletotrichum gloeosporioides SANK 21404.

Colletoic acid, a novel 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor, was found and isolated from the cultured broth of the producing fungus Colletotrichum gloeosporioides SANK 21404. Its structure was determined to be a novel acorene-type sesquiterpene by several spectroscopic methods. The absolute structure of colletoic acid was established using a modified Mosher's method and single-crystal X-ray diffraction analysis.

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 IC(50) 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 mug/ml, respectively. These biological properties indicate that pleofungins belong to a novel class of IPC synthase inhibitors efficacious against A. fumigatus.

Pleofungins, novel inositol phosphorylceramide synthase inhibitors, from Phoma sp. SANK 13899. II. Structural elucidation.

Pleofungins (formerly called F-15078) A, B, C and D, novel depsipeptide antifungal antibiotics, were found in a mycelium extract of the producing fungus, Phoma sp. SANK 13899. The structures of pleofungins A, B, C and D were elucidated mainly by various NMR studies. The absolute configurations of the amino acids and N-methyl amino acids of pleofungin A constituents in the hydrolysate were determined by the application of advanced Marfey's method in combination with gas chromatography/mass spectrometry analysis of their silylation products with N-methyl-N-(tert-butylsilyl)trifluoroacetamide. Two alpha-hydroxy acid constituents, alpha-hydroxyisocaproic acid and alpha-hydroxyisovaleric acid, were isolated from the hydrolysate and their stereochemistries were determined by their specific rotations.