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
Author Information
Jeff S Piotrowski: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703; jpiotrowski@wisc.edu ohya@k.u-tokyo.ac.jp.
Hiroki Okada: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan 277-8561;
Fachuang Lu: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
Sheena C Li: RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan 351-0198;
Li Hinchman: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
Ashish Ranjan: Departments of Plant Pathology and.
Damon L Smith: Departments of Plant Pathology and.
Alan J Higbee: Chemistry, University of Wisconsin-Madison, Madison, WI 53706;
Arne Ulbrich: Chemistry, University of Wisconsin-Madison, Madison, WI 53706;
Joshua J Coon: Chemistry, University of Wisconsin-Madison, Madison, WI 53706;
Raamesh Deshpande: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN 55455; and.
Yury V Bukhman: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
Sean McIlwain: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
Irene M Ong: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
Chad L Myers: Department of Computer Science and Engineering, University of Minnesota-Twin Cities, Minneapolis, MN 55455; and.
Charles Boone: RIKEN Center for Sustainable Resource Science, Wako, Saitama, Japan 351-0198; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, Canada M5S 3E1.
Robert Landick: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
John Ralph: Great Lakes Bioenergy Research Center, University of Wisconsin-Madison, Madison, WI 53703;
Mehdi Kabbage: Departments of Plant Pathology and.
Yoshikazu Ohya: Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba, Japan 277-8561; jpiotrowski@wisc.edu ohya@k.u-tokyo.ac.jp.
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.
