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An antitumor antibiotic, tyroscherin, was isolated from the culture of a fungus identified as Pseudallescheria sp. The structure of tyroscherin including the absolute stereochemistry was determined as shown in Fig. 1 by NMR and degradation studies. Tyroscherin selectively inhibited IGF-1-dependent growth of MCF-7 human breast cancer cells with an IC50 of 9.7 ng/ml.

A novel antifungal antibiotic, YM-193221, was found in the culture broth of a fungus, Pseudallescheria ellipsoidea. The structure of the antibiotic was determined through several spectroscopic experiments as 2-dimethylamino-1-(4-hydroxyphenyl)-8,10-dimethyl-6-dodecene-3-one. YM-193221 exhibited potent antifungal activity against Candida albicans and also inhibited mannan synthesis in the yeast cell wall.

Through our screening for novel antifungal compounds, YM-215343 was found in the culture extract of Phoma sp. QN04621. The structure of YM-215343 was determined by several spectroscopic experiments as a novel compound closely related to apiosporamide and fischerin. YM-215343 exhibited antifungal activity against the pathogenic fungi, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus with MIC values of 2 to approximately 16 microg/ml. It also showed cytotoxicity against HeLa S3 cells with an IC50 of 3.4 microg/ml.

The structure of oximidine III, a new antitumor antibiotic against transformed cells from Pseudomonas sp. QN05727, was determined to be a benzolactone enamide containing an O-methyloxime moiety as shown in Fig. 1 by NMR spectral analysis including a variety of two-dimensional techniques.

Our screening for antitumor antibiotics against transformed cells resulted in the isolation of a new active metabolite, oximidine III, from Pseudomonas sp. QN05727. This substance selectively inhibited the growth of rat 3Y1 fibroblasts transformed with various oncogenes. In ras- or src-transformed cells, oximidine III arrested the cell cycle at G1 phase and increased the expression of p21WAF1.

A new compound, gerfelin, was isolated from a culture broth of Beauveria felina QN22047. It was purified by column chromatography on silica gel and by HPLC. Gerfelin has the molecular formula C15H14O6. It inhibited synthesis of geranylgeranyl diphosphate, which was mediated by recombinant human geranylgeranyl diphosphate synthase (hGGPP synthase) in vitro. The inhibitory pattern of gerfelin was noncompetitive against isopentenyl diphosphate, and uncompetitive against farnesyl diphosphate.

A novel platelet aggregation inhibitor, YM-254890, was isolated from the culture broth of strain QS3666. This strain was isolated from a soil sample collected at Okutama, Tokyo, Japan, and was identified as Chromobacterium sp. by morphological and physiological criteria. YM-254890 was purified from the culture supernatant by solvent extraction, ODS and silica gel flash chromatography, followed by preparative HPLC. YM-254890 inhibited ADP-induced platelet aggregation in human platelet-rich plasma with an IC50 value below 0.6 microM by blocking the P2Y1 receptor-signal transduction pathway.

YM-266183 and YM-266184 are new antibacterial substances that have activity against drug-resistant bacteria produced by Bacillus cereus QN03323. These structures were elucidated by MS and NMR spectral analysis. YM-266183 and YM-266184 are the cyclic thiopeptides containing thiazole and pyridine moieties, and several unusual amino acids.

Novel antibiotics, YM-266183 (1) and YM-266184 (2), were found in the culture broth of Bacillus cereus QN03323 which was isolated from the marine sponge Halichondria japonica. The structures of both antibiotics were determined by several spectroscopic experiments as new thiopeptide compounds. They exhibited potent antibacterial activities against staphylococci and enterococci including multiple drug resistant strains, whereas they were inactive against Gram-negative bacteria.

A new antifungal antibiotic, YM-202204 (1), was found in the culture broth of marine fungus Phoma sp. Q60596. The structure of 1 was determined by several spectroscopic experiments as a new lactone compound. This antibiotic exhibited potent antifungal activities against Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus, and also inhibited glycosyl-phosphatidyl-inositol (GPI)-anchoring in yeast cells.

A novel benz[a]anthraquinone, YM-181741, was isolated from the culture broth of actinomycete strain Q57219. The strain was identified as Streptomyces sp. by morphological and chemotaxonomic characterization. YM-181741 was purified from the culture supernatant by serial column chromatography. The structure of YM-181741 was determined by spectroscopic analysis including one- and two-dimensional NMR experiments. YM-181741 showed selective anti-Helicobacterpylori activity with a MIC value of 0.2 microg/ml.