Masami Ezaki

WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. no. 89009. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities.

WS009 A and B novel endothelin receptor antagonists, have been isolated from the fermentation broth of Streptomyces sp. No. 89009. These antagonists were purified from the culture filtrate followed by Diaion SP-207, DEAE Toyopearl column chromatography and HPLC. WS009 A and B showed selective activity in an endothelin receptor binding assay with IC50 of 5.8 x 10(-6) M and 6.7 x 10(-7) M, respectively. On the basis of spectroscopic and chemical evidence, the structures of WS009 A and B have been established as 1 and 3, and are highly hydroxylated benz[a]anthraquinone chromophores.

FR207944, an Antifungal Antibiotic from Chaetomium sp. No. 217 I. Taxonomy, Fermentation, and Biological Properties

An antifungal antibiotic, FR207944, was isolated from the culture broth of a fungal strain Chaetomium sp. no. 217. FR207944 is a triterpene glucoside with antifungal activity against Aspergillus fumigatus and Candida albicans. Specifically, FR207944 exhibits in vitro and in vivo antifungal activity against A. fumigatus. The effects of FR207944 on the morphology of A. fumigatus were shown to be similar to those of FR901379, a known 1,3-β-glucan synthase inhibitor. The MECs of FR207944 against A. fumigatus FP1305 and C. albicans FP633 in micro-broth dilution test were 0.039 and 1.6 μg/ml respectively. FR207944 showed good potency by subcutaneous injection and oral administration against A. fumigatus in a murine systemic infection model, with ED50s of 5.7 and 17 mg/kg respectively.

Naphthalecin, a Novel Antibiotic Produced by the Anaerobic Bacterium, Sporotalea colonica sp. nov.

A novel antibiotic naphthalecin was purified and isolated from the cells of an anaerobic bacterium isolated from a soil sample. This antibiotic contained a naphthalene moiety, so named as naphthalecin, and showed antibacterial activity against gram positive species. The producing strain, an obligate anaerobe, was identified as a new species of the genus Sporotalea. Identification of the bacterium, cultivation, purification, structure determination, and antibacterial activity are shown.

KB425796-A, a novel antifungal antibiotic produced by Paenibacillus sp. 530603

The novel antifungal macrocyclic lipopeptidolactone, KB425796-A (1), was isolated from the fermentation broth of bacterial strain 530603, which was identified as a new Paenibacillus species based on morphological and physiological characteristics, and 16S rRNA sequences. KB425796-A (1) was isolated as white powder by solvent extraction, HP-20 and ODS-B column chromatography, and lyophilization, and was determined to have the molecular formula C79H115N19O18. KB425796-A (1) showed antifungal activities against Aspergillus fumigatus and the micafungin-resistant infectious fungi Trichosporon asahii, Rhizopus oryzae, Pseudallescheria boydii and Cryptococcus neoformans.

Identification of ten KB425796-A congeners from Paenibacillus sp. 530603 using an antifungal assay against Aspergillus fumigatus in combination with micafungin

The discovery and characterization of natural congeners is one approach for understanding the relationship between chemical structure and biological function. We recently isolated the novel antifungal metabolite KB425796-A produced by the recently isolated bacterium Paenibacillus sp. 530603. On the basis of morphological changes of Aspergillus fumigatus induced by KB425796-A in combination with micafungin, we developed a highly sensitive screening method for the specific detection of KB425796-A congeners. Using this method, we isolated ten congeners of KB425796-A, named KB425796-B, -C, -D, -E, -F, -G, -H, -I, -J and -K, which exhibited diverse antifungal potencies against A. fumigatus. One of the most potent congeners, KB425796-C, had antifungal activities against several micafungin-resistant infectious fungi. KB425796-C can be a potential drug candidate for treating micafungin-resistant fungal infections.