Piotrowski JS~Ohya Y, 2015

Pubmed ID 25775513
Title Plant-derived antifungal agent poacic acid targets β-1,3-glucan.
Authors Jeff S Piotrowski, Hiroki Okada, Fachuang Lu, Sheena C Li, Li Hinchman, Ashish Ranjan, Damon L Smith, Alan J Higbee, Arne Ulbrich, Joshua J Coon, Raamesh Deshpande, Yury V Bukhman, Sean McIlwain, Irene M Ong, Chad L Myers, Charles Boone, Robert Landick, John Ralph, Mehdi Kabbage, Yoshikazu Ohya
Abstract A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates.
Citation Proc. Natl. Acad. Sci. U.S.A. 2015; 112:E1490-7

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Papers Phenotype Conditions Collection Tested mutants Data Details
Piotrowski JS~Ohya Y, 2015 growth (relative abundance in pooled culture) poacic acid [88 ug/ml] drug-sensitized hap a ~4,000 Quantitative

Curation history

June 10, 2016 Tested strains not relevant.
June 10, 2016 Data not relevant.