Skip to main content
U.S. Department of Energy
Office of Scientific and Technical Information

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];  [3];  [4];  [3];  [5];  [5];  [6];  [6];  [6];  [7];  [3];  [3];  [3];  [7];  [8];  [3];  [3];  [5];  [2]
  1. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center; DOE Office of Scientific and Technical Information (OSTI)
  2. Univ. of Tokyo, Kashiwa (Japan). Graduate School of Frontier Sciences. Dept. of Integrated Biosciences
  3. Univ. of Wisconsin, Madison, WI (United States). Great Lakes Bioenergy Research Center
  4. RIKEN Center for Sustainable Resource Science, Wako (Japan)
  5. Univ. of Wisconsin, Madison, WI (United States). Dept. of Plant Pathology
  6. Univ. of Wisconsin, Madison, WI (United States). Dept. of Chemistry
  7. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Computer Science and Engineering
  8. RIKEN Center for Sustainable Resource Science, Wako (Japan); Univ. of Toronto, ON (Canada). Terrence Donnelly Centre for Cellular and Biomolecular Research

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) (SC-23); National Inst. of Health (NIH) (United States); National Science Foundation (NSF) (United States); 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
OSTI ID:
1348356
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 12 Vol. 112; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English

References (65)

Exploring the Mode-of-Action of Bioactive Compounds by Chemical-Genetic Profiling in Yeast journal August 2006
Inhibition of colonization by a native arbuscular mycorrhizal fungal community via Populus trichocarpa litter, litter extract, and soluble phenolic compounds journal March 2008
Systematic exploration of synergistic drug pairs journal January 2011
Characterization of Mutations in the Iron-Sulphur Subunit of Succinate Dehydrogenase Correlating with Boscalid Resistance in Alternaria alternata from California Pistachio journal June 2008
Climate Change and Infectious Diseases: From Evidence to a Predictive Framework journal August 2013
Synergistic Activities of Three Triazoles with Caspofungin against Candida glabrata Isolates Determined by Time-Kill, Etest, and Disk Diffusion Methods journal March 2010
Single-cell phenomics reveals intra-species variation of phenotypic noise in yeast journal January 2013
Hydrolysis of Lignocellulosic Materials for Ethanol Production: A Review journal January 2003
Diferulates as structural components in soluble and insoluble cereal dietary fibre journal January 2001
Saccharomyces cerevisiae YCRO17c/CWH43 encodes a putative sensor/transporter protein upstream of the BCK2 branch of the PKC1-dependent cell wall integrity pathway: Cwh43p, a sensor/transporter-like protein implicated in cell wall integrity journal April 2001
The influence of Congo red on the cell wall and (1 → 3)-β-d-glucan microfibril biogenesis in Saccharomyces cerevisiae journal July 1992
Trichoderma harzianum SQR-T037 rapidly degrades allelochemicals in rhizospheres of continuously cropped cucumbers journal October 2010
Identification of glycolaldehyde as the key inhibitor of bioethanol fermentation by yeast and genome-wide analysis of its toxicity journal October 2010
Effects of copper fungicide residues on the microbial function of vineyard soils journal August 2012
Hydrolysis of lignocellulosic materials for ethanol production: a review journal May 2002
Fermentation of lignocellulosic hydrolysates. II: inhibitors and mechanisms of inhibition journal August 2000
A biorefinery processing perspective: Treatment of lignocellulosic materials for the production of value-added products journal December 2010
Combining functional genomics and chemical biology to identify targets of bioactive compounds journal February 2011
A rapid resazurin bioassay for assessing the toxicity of fungicides journal March 2009
A parametric analysis of future ethanol use in the light-duty transportation sector: Can the US meet its Renewable Fuel Standard goals without an enforcement mechanism? journal February 2014
A Lipid E-MAP Identifies Ubx2 as a Critical Regulator of Lipid Saturation and Lipid Bilayer Stress journal August 2013
Long-term copper application in an organic vineyard modifies spatial distribution of soil micro-organisms journal October 2013
Cell Wall Cross-Linking in Grasses by Ferulates and Diferulates book August 1998
Unbiased Screening of Marine Sponge Extracts for Anti-inflammatory Agents Combined with Chemical Genomics Identifies Girolline as an Inhibitor of Protein Synthesis journal October 2013
Diferulate Content of Maize Sheaths Is Associated with Resistance to the Mediterranean Corn Borer Sesamia nonagrioides (Lepidoptera:  Noctuidae) journal November 2006
Ferulic acid may prevent infection of Cicer arietinum by Sclerotium rolfsii journal January 2003
Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates journal January 2013
Profiling of diferulates (plant cell wall cross-linkers) using ultrahigh-performance liquid chromatography-tandem mass spectrometry journal January 2013
Movement of yeast 1,3-beta-glucan synthase is essential for uniform cell wall synthesis journal January 2002
Two homologous genes, DCW1 (YKL046c) and DFG5, are essential for cell growth and encode glycosylphosphatidylinositol (GPI)-anchored membrane proteins required for cell wall biogenesis in Saccharomyces cerevisiae: GPI-anchored protein involved in cell wall biosynthesis journal November 2002
High-dimensional and large-scale phenotyping of yeast mutants journal December 2005
Cellulosic ethanol production from AFEX-treated corn stover using Saccharomyces cerevisiae 424A(LNH-ST) journal January 2009
Yeast 1,3-β-Glucan Synthase Activity Is Inhibited by Phytosphingosine Localized to the Endoplasmic Reticulum journal May 2001
Interruption of Inositol Sphingolipid Synthesis Triggers Stt4p-dependent Protein Kinase C Signaling journal October 2010
A Novel Endoplasmic Reticulum Membrane Protein Rcr1 Regulates Chitin Deposition in the Cell Wall of Saccharomyces cerevisiae journal December 2004
Lysis of growing yeast-form cells of Candida albicans by echinocandin: A cytological study journal January 1981
Lack of GTP-bound Rho1p in secretory vesicles of Saccharomyces cerevisiae journal July 2003
Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data journal January 2014
Distinct roles of cell wall biogenesis in yeast morphogenesis as revealed by multivariate analysis of high-dimensional morphometric data journal January 2014
GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes journal August 2004
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data journal November 2009
Yeast Nap1-Binding Protein Nbp2p Is Required for Mitotic Growth at High Temperatures and for Cell Wall Integrity journal October 2003
Identification of Genes Involved in the Toxic Response of Saccharomyces cerevisiae against Iron and Copper Overload by Parallel Analysis of Deletion Mutants journal September 2007
Identification of Genes Involved in the Toxic Response of Saccharomyces cerevisiae against Iron and Copper Overload by Parallel Analysis of Deletion Mutants journal March 2008
Characterization of Mutations in the Iron-Sulphur Subunit of Succinate Dehydrogenase Correlating with Boscalid Resistance in Alternaria alternata from California Pistachio journal June 2008
Quantitative phenotyping via deep barcode sequencing journal July 2009
INHIBITION OF Saccharomyces cerevisiae BY NATURALLY OCCURRING HYDROXYCINNAMATES journal May 1980
Characterization and Gene Cloning of 1,3-beta-D-Glucan Synthase from Saccharomyces Cerevisiae journal August 1995
Characterization and Gene Cloning of 1,3-beta-D-Glucan Synthase from Saccharomyces Cerevisiae journal August 1995
Fungicide Resistance Phenotypes of Botrytis cinerea Isolates from Commercial Vineyards in South West Germany: Fungicide Resistance of B. cinerea Isolates from Vineyards journal December 2010
Analysis of the biological activity of a novel 24-membered macrolide JBIR-19 in Saccharomyces cerevisiae by the morphological imaging program CalMorph journal January 2012
Identification of furfural as a key toxin in lignocellulosic hydrolysates and evolution of a tolerant yeast strain journal November 2008
The Genetic Landscape of a Cell journal January 2010
Synergistic Activities of Three Triazoles with Caspofungin against Candida glabrata Isolates Determined by Time-Kill, Etest, and Disk Diffusion Methods journal March 2010
Assessing Resistance to the Echinocandin Antifungal Drug Caspofungin in Candida albicans by Profiling Mutations in FKS1 journal May 2006
Topological and Mutational Analysis of Saccharomyces cerevisiae Fks1 journal May 2012
The Yeast Protein Kinase C Cell Integrity Pathway Mediates Tolerance to the Antifungal Drug Caspofungin through Activation of Slt2p Mitogen-Activated Protein Kinase Signaling journal December 2003
Climate Change Effects on Plant Disease: Genomes to Ecosystems journal September 2006
Pancreas Cell Physiology and Pancreatitis Cell Biology journal January 2003
High-Content, Image-Based Screening for Drug Targets in Yeast journal April 2010
Vanillin Inhibits Translation and Induces Messenger Ribonucleoprotein (mRNP) Granule Formation in Saccharomyces cerevisiae: Application and Validation of High-Content, Image-Based Profiling journal April 2013
Design and Analysis of Bar-seq Experiments journal November 2013
Antifungal Resistance Trends Towards the Year 2000: Implications for Therapy and New Approaches journal January 1997
Death by a thousand cuts: the challenges and diverse landscape of lignocellulosic hydrolysate inhibitors journal March 2014
Profiling of diferulates (plant cell wall cross-linkers) using ultrahigh-performance liquid chromatography-tandem mass spectrometry text January 2013

Cited By (5)

Identification of Fungicide Targets in Pathogenic Fungi book January 2018
Using BEAN-counter to quantify genetic interactions from multiplexed barcode sequencing experiments journal January 2019
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