2018 Volume 68 Issue 2 Pages 77-82
Characterization of trichothecene hydroxylation enzymes and screening of trichothecene production inhibitors were performed to decrease the frequency of false detection and reduce grain contamination by trichothecene mycotoxins. Molecular genetic studies of trichothecene biosynthetic genes revealed that the trichothecene C-4 hydroxylase, FgTRI13p, encoded by FgTri13 of Fusarium graminearum, has co-evolved with the C-7/C-8 hydroxylase, FgTRI1p, encoded by FgTri1. FgTRI13p shows highly restricted substrate specificity for trichothecene intermediates compared with FsTRI13p produced by Fusarium sporotrichioides. A glutamine analog, acivicin, was screened as an inhibitor of trichothecene production from the chemical library of the RIKEN Natural Products Depository. The predicted mode of action of acivicin in F. graminearum was that the acivicin-induced nutrient starvation repressed the trichothecene master regulator encoded by FgTri6, which blocked trichothecene production. In addition, another trichothecene production inhibitor NPD352 [testosterone 3-(O-carboxymethyl)oxime amide-bonded to phenylalanine methyl ester] was obtained from the library by chemical array screening using trichodiene synthase (FgTRI5p) as a target protein. The mixed-type inhibitor NPD352 may bind and interfere with intracellular FgTRI5p under conditions favoring trichothecene production.
