期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 12, 页码 E1490-E1497出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1410400112
关键词
chemical genomics; high-dimensional morphometrics; lignocellulosic hydrolysates; fungal cell wall; Saccharomyces cerevisiae
资金
- Department of Energy (DOE) Great Lakes Bioenergy Research Center DOE Biological and Environmental Research Office of Science Grant [DE-FC02-07ER64494]
- Wisconsin Alumni Research Foundation Award [MSN178899]
- RIKEN Foreign Postdoctoral Fellowship
- Wisconsin Soybean Marketing Board Grant [MSN172403]
- National Institutes of Health [1R01HG005084-01A1, 1R01GM104975-01, R01HG005853]
- National Science Foundation Grant [DBI 0953881]
- Canadian Institute for Advanced Research Genetic Networks Program
- United Soybean Board Grant [MSN143317]
- Ministry of Education, Culture, Sports, Science and Technology, Japan [24370002]
- Grants-in-Aid for Scientific Research [15H04483] Funding Source: KAKEN
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0953881] Funding Source: National Science Foundation
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 beta-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding beta-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani aswell as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broadrange fungal pathogen S. sclerotiorum substantially reduced lesion development. The discovery of poacic acid as a natural antifungal agent targeting beta-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.
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