An artificial metabolic route to an unnatural trichothecene was designed by taking advantage of the broad substrate specificities of the T-2 toxin biosynthetic enzymes of Fusarium sporotrichioides. By feeding 7-hydroxyisotrichodermin, a shunt pathway metabolite of F. graminearum, to a trichodiene synthase-deficient mutant of F. sporotrichioides, 7-hydroxy T-2 toxin (1) was obtained as the final metabolite. Such an approach may have future applications in the metabolic engineering of a variety of fungal secondary metabolites. The toxicity of 7-hydroxy T-2 toxin was 10 times lower than that of T-2 toxin in HL-60 cells.
Fusarium graminearum causes a disease of wheat and barley known as Fusarium head blight. It contaminates the grains with trichothecene mycotoxins such as deoxynivalenol (DON). As shunt intermediates in the DON biosynthetic pathway, 7-hydroxyisotrichodermin (7-HIT) and 8-hydroxyisotrichodermin (8-HIT) are known. However, their activities have not been previously evaluated. In this study, we performed toxicity assays of these trichothecenes by using a sensitive yeast bioassay that we have recently established. The IC 50 of 7-HIT and 8-HIT were in the range of 20-40 µg/ml, while the IC 50 of DON was approximately 1.5 µg/ml. Although the toxicity of these shunt metabolites remains to be investigated in animal systems, our present data indicate that 7-HIT and 8-HIT may not be major issues that require regulation in agricultural products.
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