4- O -Glucosylation of Trichothecenes by Fusarium Species: A Phase II Xenobiotic Metabolism for t-Type Trichothecene Producers

The t-type trichothecene producers and protect themselves against their own mycotoxins by acetylating the C-3 hydroxy group with Tri101p acetylase. To understand the mechanism by which they deal with exogenously added d-type trichothecenes, the Δ mutants expressing all but the first trichothecene pathway enzymes were fed with trichodermol (TDmol), trichothecolone (TCC), 8-deoxytrichothecin, and trichothecin. LC-MS/MS and NMR analyses showed that these C-3 unoxygenated trichothecenes were conjugated with glucose at C-4 by α-glucosidic linkage. As t-type trichothecenes are readily incorporated into the biosynthetic pathway following the C-3 acetylation, the mycotoxins were fed to the Δ Δ mutant to examine their fate. LC-MS/MS and NMR analyses demonstrated that the mutant conjugated glucose at C-4 of HT-2 toxin (HT-2) by α-glucosidic linkage, while the Δ mutant metabolized HT-2 to 3-acetyl HT-2 toxin and T-2 toxin. The 4- -glucosylation of exogenously added t-type trichothecenes appears to be a general response of the Δ Δ mutant, as nivalenol and its acetylated derivatives appeared to be conjugated with hexose to some extent. The toxicities of 4- -glucosides of TDmol, TCC, and HT-2 were much weaker than their corresponding aglycons, suggesting that 4- -glucosylation serves as a phase II xenobiotic metabolism for t-type trichothecene producers.