Yatakemycin, a novel antifungal antibiotic produced by Streptomyces sp. TP-A0356.
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.
Igarashi
Yasuhiro
Y
Biotechnology Research Center, Toyama Prefectural University, 5180, Kurokawa, Kosugi, Toyama 939-0398, Japan. yas@pu-toyama.ac.jp
Futamata
Katsuyuki
K
Fujita
Tsuyoshi
T
Sekine
Akira
A
Senda
Hisato
H
Naoki
Hideo
H
Furumai
Tamotsu
T
D000935:Antifungal Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D000080890:Duocarmycins; D005285:Fermentation; D007211:Indoles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D008970:Molecular Weight; D019906:Nuclear Magnetic Resonance, Biomolecular; D011758:Pyrroles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D011760:Pyrrolidinones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013302:Streptomyces / Q000737:chemistry* / Q000145:classification / Q000378:metabolism
D000935:Antifungal Agents; D000080890:Duocarmycins; D007211:Indoles; D011758:Pyrroles; D011760:Pyrrolidinones; C474180:yatakemycin