Viridiofungins, novel inhibitors of sphingolipid synthesis

Viridiofungins, novel inhibitors of sphingolipid synthesis
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DOI:
10.7164/antibiotics.50.339
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发表时间:
1997-04-01
影响因子:
3.3
通讯作者:
Kurtz, MB
Kurtz, MB
中科院分区:
医学4区
文献类型:
--
作者:
Mandala, SM;Thornton, RA;Kurtz, MB

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绿霉素是广谱抗真菌剂,其在体外抑制角鲨烯合酶,但在全细胞中不特异性抑制真菌麦角固醇合成,表明抗真菌活性的不同作用模式。在这份报告中,我们表明,viridiofungins是有效的丝氨酸棕榈酰转移酶,在鞘脂生物合成的第一个承诺的酶在体外抑制剂,其抗真菌活性是由于抑制鞘脂的合成。具有相同作用模式的其他相关成分从生产培养物绿色木霉中分离出来,并抑制丝氨酸棕榈酰转移酶和抗真菌活性。
Viridiofungins are broad spectrum antifungal agents that inhibit the squalene synthase in vitro, but do not specifically inhibit fungal ergosterol synthesis in whole cells, indicating a different mode of action for antifungal activity. In this report, we show that viridiofungins are potent in vitro inhibitors of serine palmitoyltransferase, the first committed enzyme in sphingolipid biosynthesis, and their antifungal activity is due to inhibition of sphingolipid synthesis. Additional related components with the same mode of action were isolated from the producing culture, Trichoderma viride, and inhibition of the serine palmitoyltransferase and antifungal activity is presented.