Gramiketides, Novel Polyketide Derivatives of , Are Produced during the Infection of Wheat.

The plant pathogen is a proficient producer of mycotoxins and other in part still unknown secondary metabolites, some of which might act as virulence factors on wheat. The gene is expressed only , so far hampering the identification of an associated metabolite. Here we combined the activation of silent gene clusters by chromatin manipulation () with blocking the metabolic flow into the competing biosynthesis of the two major mycotoxins deoxynivalenol and zearalenone. Using an untargeted metabolomics approach, two closely related metabolites were found in triple mutants ( deficient in production of the major mycotoxins deoxynivalenol and zearalenone, but not in strains with an additional deletion in . Characterization of the metabolites, by LC-HRMS/MS in combination with a stable isotope-assisted tracer approach, revealed that they are likely hybrid polyketides comprising a polyketide part consisting of malonate-derived acetate units and a structurally deviating part. We propose the names gramiketide A and B for the two metabolites. In a biological experiment, both gramiketides were formed during infection of wheat ears with wild-type but not with mutants. The formation of the two gramiketides during infection correlated with that of the well-known virulence factor deoxynivalenol, suggesting that they might play a role in virulence.