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Title: Plant-derived antifungal agent poacic acid targets β-1,3-glucan

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [1];  [3];  [1];  [4];  [4];  [5];  [5];  [5];  [6];  [1];  [1];  [1];  [6];  [7];  [1];  [1];  [4];  [2]
  1. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center
  2. Univ. of Tokyo, Kashiwa (Japan). Graduate School of Frontier Sciences. Dept. of Integrated Biosciences
  3. RIKEN Center for Sustainable Resource Science, Wako (Japan)
  4. Univ. of Wisconsin, Madison, WI (United States). Dept. of Plant Pathology
  5. Univ. of Wisconsin, Madison, WI (United States). Dept. of Chemistry
  6. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Computer Science and Engineering
  7. RIKEN Center for Sustainable Resource Science, Wako (Japan); Univ. of Toronto, ON (Canada). Terrence Donnelly Centre for Cellular and Biomolecular Research
+ Show Author Affiliations

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. In conclusion, 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.

Research Organization:
Univ. of Wisconsin, Madison, WI (United States); Univ. of Minnesota, Minneapolis, MN (United States); Univ. of Toronto, ON (Canada); Univ. of Tokyo, Kashiwa (Japan)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Inst. of Health (NIH) (United States); National Science Foundation (NSF); Wisconsin Alumni Research Foundation (United States); Wisconsin Soybean Marketing Board (United States); Canadian Inst. for Advanced Research Genetic Networks Program (Canada); United Soybean Board (United States); Ministry of Education, Culture, Sports, Science and Technology (Japan)
Contributing Organization:
RIKEN Center for Sustainable Resource Science, Wako (Japan)
Grant/Contract Number:
FC02-07ER64494; MSN178899; MSN143317; MSN172403; 1R01HG005084-01A1; DBI 0953881; R01HG005853; 24370002; 1R01GM104975-01
OSTI ID:
1348356
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 12; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 72 works
Citation information provided by
Web of Science

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Cited By (5)

Identification of Fungicide Targets in Pathogenic Fungi book January 2018
A global genetic interaction network maps a wiring diagram of cellular function journal September 2016
Decyl Gallate as a Possible Inhibitor of N-Glycosylation Process in Paracoccidioides lutzii
  • de Paula e. Silva, Ana Carolina Alves; de Oliveira, Haroldo Cesar; Scorzoni, Liliana
  • Antimicrobial Agents and Chemotherapy, Vol. 63, Issue 11 https://doi.org/10.1128/aac.01909-18
journal August 2019
A comparative study of the enzymatic hydrolysis of batch organosolv-pretreated birch and spruce biomass journal July 2018
Using BEAN-counter to quantify genetic interactions from multiplexed barcode sequencing experiments journal January 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Saccharomyces cerevisiae
chemical genomics
fungal cell wall
high-dimensional morphometrics
lignocellulosic hydrolysates