Carbendazim-resistance associated β2-tubulin substitutions increase deoxynivalenol biosynthesis by reducing the interaction between β2-tubulin and IDH3 in Fusarium graminearum

Microtubule is a well-known structural protein participating in cell division, motility and vesicle traffic. In this study, we found that beta(2)-tubulin, one of the microtubule components, plays an important role in regulating secondary metabolite deoxynivalenol (DON) biosynthesis in Fusarium graminearum by interacting with isocitrate dehydrogenase subunit 3 (IDH3). We found IDH3 negatively regulate DON biosynthesis by reducing acetyl-CoA accumulation in F. graminearum and DON biosynthesis was stimulated by exogenous acetyl-CoA. In addition, the expression of IDH3 significantly decreased in the carbendazim-resistant mutant nt167 (Fg beta(F167Y)(2)). Furthermore, we found that carbendazim-resistance associated beta(2)-tubulin substitutions reducing the interaction intensity between beta(2)-tubulin and IDH3. Interestingly, we demonstrated that beta(2)-tubulin inhibitor carbendazim can disrupt the interaction between beta(2)-tubulin and IDH3. The decreased interaction intensity between beta(2)-tubulin and IDH3 resulted in the decreased expression of IDH3, which can cause the accumulation of acetyl-CoA, precursor of DON biosynthesis in F. graminearum. Thus, we revealed that carbendazim-resistance associated beta(2)-tubulin substitutions or carbendazim treatment increases DON biosynthesis by reducing the interaction between beta(2)-tubulin and IDH3 in F. graminearum. Taken together, the novel findings give the new perspectives of beta(2)-tubulin in regulating secondary metabolism in phytopathogenic fungi.