VIRIDIOFUNGINS, NOVEL INHIBITORS OF SPHINGOLIPID SYNTHESIS

Viridiofungins are broad spectrum antifungal agents that inhibit the s qualene synthase in vitro, but do not specifically inhibit fungal ergo sterol 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 fir st committed enzyme in sphingolipid biosynthesis, and their antifungal activity is due to inhibition of sphingolipid synthesis. Additional r elated components with the same mode of action were isolated from the producing culture, Trichoderma viride, and inhibition of the serine pa lmitoyltransferase and antifungal activity is presented.