Abstract
In the screening of novel antifungal compounds, yatakemycin was found in the culture broth of Streptomyces sp. TP-A0356. Yatakemycin was obtained by solvent extraction of the fermentation broth and chromatographic purification using ODS column and preparative HPLC. The structure of yatakemycin was elucidated by NMR and CID-MS/MS experiments as a novel antibiotic belonging to a family of CC-1065 and duocarmycins known to be DNA alkylating agents. Yatakemycin inhibited the growth of pathogenic fungi such as Aspergillus fumigatus and Candida albicans with the MIC values of 0.01-0.03 microg/ml, more potent than amphotericin B (MIC: 0.1-0.5 microg/ml) or itraconazole (MIC: 0.03-0.2 microg/ml). It also showed potent cytotoxicity against cancer cell lines with the IC50 of 0.01-0.3 microg/ml.
MeSH terms
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Antifungal Agents / biosynthesis
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Antifungal Agents / chemistry*
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Antifungal Agents / isolation & purification
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Antifungal Agents / pharmacology
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Aspergillus fumigatus / drug effects
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Candida albicans / drug effects
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Chromatography, Gel
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Chromatography, High Pressure Liquid
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Duocarmycins
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Fermentation
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Indoles / chemistry*
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Indoles / isolation & purification
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Indoles / pharmacology
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Microbial Sensitivity Tests
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Microscopy, Electron, Scanning
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Molecular Structure
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Molecular Weight
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Nuclear Magnetic Resonance, Biomolecular
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Pyrroles / chemistry*
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Pyrroles / isolation & purification
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Pyrroles / pharmacology
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Pyrrolidinones / chemistry*
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Pyrrolidinones / isolation & purification
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Pyrrolidinones / pharmacology
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Spectrometry, Mass, Fast Atom Bombardment
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Spectrophotometry, Infrared
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Spectrophotometry, Ultraviolet
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Streptomyces / chemistry*
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Streptomyces / classification
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Streptomyces / metabolism
Substances
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Antifungal Agents
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Duocarmycins
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Indoles
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Pyrroles
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Pyrrolidinones
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yatakemycin