Nose Hiroshi, Fushimi Hideki, Seki Asako, Sasaki Toru, Watabe Hiroomi, Hoshiko Shigeru
Drug Discovery, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama 222-0002, Japan.
J Antibiot (Tokyo). 2002 Nov;55(11):969-74. doi: 10.7164/antibiotics.55.969.
PF1163A and B are a pair of antifungal agents isolated from a fermentation broth of Penicillium sp. PF1163A inhibited ergosterol synthesis in Saccharomyces cerevisiae, resulting in an accumulation of 4,4-dimethylzymosterol and a decrease of ergosterol. The ERG25 strain overexpressing the ERG25 gene was resistant to PF1163A. ERG25p is a C-4 sterol methyl oxidase known to be essential for the viability of yeast and fungi because of the known role of ERG25 gene disruption in S. cerevisiae-led lethality. ERG25p is the enzyme responsible for the first step in the removal of the two methyl groups at the C-4 position of sterol. From the results obtained here, we conclude that PF1163A is a novel natural antifungal that inhibits C-4 sterol methyl oxidase.
PF1163A和PF1163B是从青霉菌属的发酵液中分离出的一对抗真菌剂。PF1163A抑制酿酒酵母中麦角甾醇的合成，导致4,4-二甲基酵母甾醇积累和麦角甾醇减少。过表达ERG25基因的ERG25菌株对PF1163A具有抗性。ERG25p是一种C-4甾醇甲基氧化酶，由于已知ERG25基因破坏会导致酿酒酵母致死，所以它对酵母和真菌的生存至关重要。ERG25p是负责去除甾醇C-4位上两个甲基第一步反应的酶。根据此处获得的结果，我们得出结论，PF1163A是一种新型天然抗真菌剂，可抑制C-4甾醇甲基氧化酶。
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