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United States Department of Agriculture

Agricultural Research Service

Research Project: MOLECULAR AND GENETIC APPROACHES TO SUPPRESSING FUNGAL PATHOGENS AND MYCOTOXIN CONTAMINATION

Location: Foodborne Toxin Detection and Prevention

Title: Natural Products as Tools for Chemogenomic Analysis of Mycotoxin Biosynthesis and Fungal Stress-Response Systems

Authors
item Campbell, Bruce
item Kim, Jong Heon
item Yu, Jiujiang
item Molyneux, Russell
item Mahoney, Noreen
item Palumbo, Jeffrey
item Chan, Kathleen
item Bhatnagar, Deepak
item Cleveland, Thomas
item Nierman, William -

Submitted to: American Chemical Society Symposium Series
Publication Type: Book / Chapter
Publication Acceptance Date: March 21, 2007
Publication Date: October 14, 2008
Citation: Campbell, B.C., Kim, J.H., Yu, J., Molyneux, R.J., Mahoney, N.E., Palumbo, J.D., Chan, K.L., Bhatnagar, D., Cleveland, T.E., Nierman, W.C. 2008. Natural Products as Tools for Chemogenomic Analysis of Mycotoxin Biosynthesis and Fungal Stress-Response Systems. American Chemical Society Symposium Series. In: Siantar, D.P. Trucksess, M., Scott, P.M., Herman, E.M. editors, Food Contaminants: Mycotoxins and Food Allergens. Oxford University Press. p. 2-11.

Interpretive Summary: Certain phenolics having antioxidative activity can inhibit aflatoxin biosynthesis by Aspergillus flavus, with no effect on fungal growth. Contrastingly, exposing A. flavus to oxidative stress, such as hydrogen peroxide, enhances aflatoxin biosynthesis. Use of gene-deletion mutants of Saccharomyces cerevisiae, as a model fungus, suggested phenolics and reactive oxygen species modulated the antioxidative stress-response system. Analysis using A. flavus microarrays showed that treatment with an anti-aflatoxigenic phenolic resulted in significant down-regulation of genes in the aflatoxin biosynthetic gene cluster, starting with pksA, a polyketide synthase gene. There was little change in expression by laeA and aflR, genes thought to modulate synthesis. These results show that antioxidative stress response genes are pivotal to modulating expression of this cluster. Use of phenolics to inhibit ochratoxin production by A. alliaceus and synergize commercial fungicides and antifungal drugs, by disrupting mitochondrial respiratory, pH regulatory, vacuolar H(+)-ATPase and mitogen-activated protein kinase (MAPK) systems, will be discussed.

Technical Abstract: Certain phenolics having antioxidative activity can inhibit aflatoxin biosynthesis by Aspergillus flavus, with no effect on fungal growth. Contrastingly, exposing A. flavus to oxidative stress, such as hydrogen peroxide, enhances aflatoxin biosynthesis. Use of gene-deletion mutants of Saccharomyces cerevisiae, as a model fungus, suggested phenolics and reactive oxygen species modulated the antioxidative stress-response system. Analysis using A. flavus microarrays showed that treatment with an anti-aflatoxigenic phenolic resulted in significant down-regulation of genes in the aflatoxin biosynthetic gene cluster, starting with pksA, a polyketide synthase gene. There was little change in expression by laeA and aflR, genes thought to modulate synthesis. These results show that antioxidative stress response genes are pivotal to modulating expression of this cluster. Use of phenolics to inhibit ochratoxin production by A. alliaceus and synergize commercial fungicides and antifungal drugs, by disrupting mitochondrial respiratory, pH regulatory, vacuolar H(+)-ATPase and mitogen-activated protein kinase (MAPK) systems, will be discussed.

Last Modified: 4/19/2014