Inhibition of trichothecin and ergosterol biosynthesis in Trichothecium roseum by lovastatin

The effect of lovastatin, an HMG-CoA reductase inhibitor, on the biosynthes is of trichothecin, ergosterol, and fatty acids in the fungus Trichothecium roseum was investigated. Treatment of lovastatin (50 mu M) to a 5-day-old culture of T. roseum reduced the incorporation of [2-C-14]acetate into tric hothecin by 79%, whereas the conversion of [5-H-3]mevalonate into this sesq uiterpenoid mycotoxin was reduced by only 28%. In a parallel experiment, th e incorporation of [2-C-14]acetate and [5-H-3]mevalonate into ergosterol we re de creased by 78% and 17%, respectively. Meanwhile, the conversion of la beled acetate into fatty acids was not significantly affected. These result s indicate that HMG-CoA reductase is a major, but not strict, regulatory si te in mevalonic acid pathway leading to the formation of trichothecin and e rgosterol. No priority was found in utilization of a single, residual meval onic acid pool in response to lovastatin inhibition for the biosynthesis of trichothecin and ergosterol. Inhibition of mevalonic acid formation does n ot significantly divert acetyl CoA into fatty acid synthesis.