Culmorin inhibits detoxification of the mycotoxin deoxynivalenol by plant UDP-glucosyltransferases

Abstract The Fusarium metabolite culmorin (CUL) frequently co-occurs with the mycotoxin deoxynivalenol (DON) on cereals. While DON is recognized as a major Fusarium virulence factor on plants, the function of CUL is still unclear. Herein, we show that CUL-deficient F. graminearum mutants created by CLM1 deletion are less aggressive on wheat than the wild-type, accompanied by increased DON-3-glucoside/DON ratios in infected wheat ears. In root elongation assays with wheat and Brachypodium distachyon, CUL had no effect alone but significantly increased the toxicity of DON. Analysis of DON/CUL-treated roots further indicated that both wheat and B. distachyon are able to glucosylate CUL and that its presence impedes DON-glucosylation in both species. We identified two B. distachyon UDP-glucosyltransferases (UGT) able to glucosylate CUL and further investigated the effect of CUL on the kinetics of validated DON-glucosylating plant UGTs (BdUGT5g03300, HvUGT13248, OsUGT79). This suggested that CUL inhibits DON-glucosylation either by serving as competitive substrate with DON or by unproductive binding. Especially BdUGT5g03300 was strongly inhibited by CUL and even its glucosides. Our results indicate that CUL contributes to Fusarium virulence by weakening plant-defenses related to UGT-catalyzed DON-detoxification. As even CUL-glucosides are potentially inhibitory to UGTs, this implies a complex synergy of CUL with DON. Highlight We present biochemical evidence that the Fusarium metabolite culmorin contributes to Fusarium virulence on plants by suppressing detoxification of the virulence factor deoxynivalenol by glucosyltransferases. Competing Interest Statement The authors have declared no competing interest. Abbreviations - (CUL) - culmorin - (DON) - deoxynivalenol - (D3G) - deoxynivalenol-3-glucoside - (TILLING) - targeting induced local lesion in genomes - (UGT) - UDP-glucosyltransferase