title: Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites.
abstract: Fusarium head blight (FHB), primarily caused byFusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins inFusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.
authors.affiliation: National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada. cuperlovim@nrc.ca.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Cuperlovic-Culf
authors.affiliation: National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada. NandhaKishore.Rajagopalan@nrc-cnrc.gc.ca.
authors.forename: NandhaKishore
authors.initials: N
authors.lastname: Rajagopalan
authors.affiliation: National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada. Dan.Tulpan@nrc-cnrc.gc.ca.
authors.forename: Dan
authors.initials: D
authors.lastname: Tulpan
authors.affiliation: National Research Council of Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada. Michele.Loewen@nrc-cnrc.gc.ca.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Loewen
keywords: Fusarium graminearum; Fusarium head blight; antifungal; biotic stress; carbonic anhydrase; cheminformatics; cytochrome P450; metabolomics; plant resistance