Wheat pathogenZymoseptoria tritici N-myristoyltransferase inhibitors: on-target antifungal activity and an unusual metabolic defense mechanism

Abstract

ABSTRACTZymoseptoria triticiis the causative agent ofSeptoria triticiblotch (STB), which costs billions of dollars annually to major wheat-producing countries in terms of both fungicide use and crop loss. Agricultural pathogenic fungi have acquired resistance to most commercially available fungicide classes, and the rate of discovery and development of new fungicides has stalled, demanding new approaches and insights. Here we investigate a potential mechanism of targeting an important wheat pathogenZ. triticivia inhibition ofN-myristoyltransferase (NMT). We characterizeZ. triticiNMT biochemically for the first time, profile thein vivo Z. triticimyristoylated proteome and identify and validate the firstZ. triticiNMT inhibitors. Proteomic investigation of the downstream effects of NMT inhibition identified an unusual and novel mechanism of defense against chemical toxicity inZ. triticithrough the application of comparative bioinformatics to deconvolute function from the previously largely unannotatedZ. triticiproteome. Research into novel fungicidal modes-of-action is essential to satisfy an urgent unmet need for novel fungicide targets, and we anticipate that this study will serve as a useful proteomics and bioinformatics resource for researchers studyingZ. tritici.