|Title:||Control of Aflatoxin Production by Targeting Aflatoxin Biosynthesis|
|Objective:||Aflatoxins (AFs) are polyketide-derived, toxic, and carcinogenic secondary metabolites produced by Aspergillus flavus on corn, peanuts, cottonseed, and tree nuts. While biosynthesis of these toxins has been extensively studied, much less is known about what causes the fungi to produce AFs under certain environmental conditions and only on certain plants.|
The goal of this proposal is to determine the dynamics of interaction among the key nutritionally and environmentally induced transcription factors necessary for production of AF in order to develop novel inhibitors to one or more of these factors to prevent AF formation in crops. We will use gene microarray, yeast two-hybrid, and chromatin immunoprecipitation assays to determine which critical AF transcription-associated proteins are affected by physiological stress, environmental and soil conditions, and interactions of the fungus with plants. Interactions among key known or to be discovered AF biosynthesis regulatory factors, such as LaeA, VeA, AflJ, and AflR, will be examined by these methods. We will examine the effects of known natural (plant-derived, such as volatile aldehydes) inhibitors of AF production on key components of the AF transcription machinery to ultimately design safe, inexpensive chemicals that inhibit proteins unique to fungal secondary metabolite biosynthesis. We expect to identify safe and effective inhibitors for applications on crops intended for consumption by humans or animals. The project will address NP108 Action Plan Component 1 Foodborne Contaminants; Problem Statement 1.B Systems Biology.
|More Info:||We expect to obtain a better understanding of transcriptional regulation of AF biosynthesis and of the effect of environmental, nutritional, and developmental factors on AF gene regulation. This is similar to the goals of Objective 1, but Objective 2 will extend the knowledge to a detailed understanding of the interactions among components of the transcriptional machinery. This knowledge is needed in order to intelligently select and develop targets for intervention strategies and to develop inhibitors that can be applied to crops safely without introducing toxicity for eukaryotes (including us and the crop plants) other than fungi.|
|Funding Source:||United States Department of Agriculture (USDA), Agricultural Research Service (ARS)|
|Institutions:||USDA/ARS - Mid South Area|
|Project Reports:||2011 Annual Report|
ARS (NP 108):
Aspergillus flavus VelB acts distinctly from VeA in conidiation and may coordinate with FluG to modulate sclerotial production
Chang P, Scharfenstein LL, Li P, Ehrlich K .
Fungal Genet Biol. 2013 Sep;58-59:71-9.
Sexuality generates diversity in the aflatoxin gene cluster: evidence on a global scale
Moore GG, Elliott JL, Singh R, Horn BW, Dorner JW, Stone EA, Chulze SN, Barros GG, Naik MK, Wright GC, Hell K, Carbone I.
PLoS Pathog. 2013 Aug;9(8):e1003574.
Genome-wide analysis of the Zn(II)₂Cys₆ zinc cluster-encoding gene family in Aspergillus flavus
Chang PK, Ehrlich KC.
Appl Microbiol Biotechnol. 2013 May;97(10):4289-300.
Testing the efficacy of eGFP-transformed Aspergillus flavus as biocontrol strains
Moore GG, Mack BM, Beltz SB.
Food and Nutrition Sciences. 2013 Apr;4(4):469-79.
Mathematic modeling for optimum conditions on aflatoxin B₁degradation by the aerobic bacterium Rhodococcus erythropolis
Kong Q, Zhai C, Guan B, Li C, Shan S, Yu J.
Toxins (Basel). 2012 Nov;4(11):1181-95.
Deletion of the Aspergillus flavus orthologue of A. nidulans fluG reduces conidiation and promotes production of sclerotia but does not abolish aflatoxin biosynthesis
Chang PK, Scharfenstein LL, Mack B, Ehrlich KC.
Appl Environ Microbiol. 2012 Nov;78(21):7557-63.
Toxigenic Aspergillus flavus and other fungi of public health concern in food and organic matter in southwest Nigeria
Fapohunda SO, Moore GG, Ganiyu OT, Beltz SB.
Mycology. 2012 Sep 6;3(3):210-9.
Identification of genetic defects in the atoxigenic biocontrol strain Aspergillus flavus K49 reveals the presence of a competitive recombinant group in field populations
Chang PK, Abbas HK, Weaver MA, Ehrlich KC, Scharfenstein LL, Cotty PJ.
Int J Food Microbiol. 2012 Mar 15;154(3):192-6.
Tight control of mycotoxin biosynthesis gene expression in Aspergillus flavus by temperature as revealed by RNA-Seq
Yu J, Fedorova ND, Montalbano BG, Bhatnagar D, Cleveland TE, Bennett JW, Nierman WC.
FEMS Microbiol Lett. 2011 Sep;322(2):145-9.
Evolutionary mechanisms involved in development of fungal secondary metabolite gene clusters - (Book / Chapter)
Accepted Publication (31-May-13)
Identification of resistance genes to Aspergillus flavus infection in peanut through genetic and genomic strategies - (Abstract Only)
Yu, J., Nierman, W.C., Guo, B. 2013. Identification of resistance genes to Aspergillus flavus infection in peanut through genetic and genomic strategies [abstract]. 6th Advances in Arachis through Genomics and Biotechnology Conference. p. 26.
The two genome sequence release and blast server construction for aflatoxin-producing L and S strains Aspergillus parasiticus and A. flavus - (Other)
Yu, J., Moore Flanagan, M.E., Ehrlich, K., Bhatnagar, D., Nierman, W.C. 2012. The two genome sequence release and blast server construction for aflatoxin-producing L and S strains Aspergillus parasiticus and A. flavus. Germplasm Release. Genome sequence releases at USDA/ARS/MSA, Stoneville, MS, and web blast server for search of gene of interest. http://10.100.124.124.4443.blast/unique.html.
Current understanding on aflatoxin biosynthesis and future perspective in reducing aflatoxin contamination - (Review Article)
Yu, J. 2012. Current understanding on aflatoxin biosynthesis and future perspective in reducing aflatoxin contamination. Toxins. 4(11):1024-1057.
The “omics” approach for solving the pre-harvest aflatoxin contamination problem: understanding the genomics and metabolomics of the fungus and proteomics of the affected corn crop - (Abstract Only)
Bhatnagar, D. 2012. The “omics” approach for solving the pre-harvest aflatoxin contamination problem: understanding the genomics and metabolomics of the fungus and proteomics of the affected corn crop. In: Fernandez-Luqueno, F., Lopez-Valdez, F., Lozano-Muniz, S., editors. Biotechnology Summit 2012 Conference, March 18-21, 2012, Yucatan, Mexico. pp. 189-193.
What can Aspergillus flavus genome offer for mycotoxin research? - (Review Article)
Yu, J., Nierman, W.C., Fedorova, N.D., Bhatnagar, D., Cleveland, T.E., Bennett, J.W. 2011. What can Aspergillus flavus genome offer for mycotoxin research? Mycological Society of China. 2(3):218-236.
The population dynamics of aflatoxigenic aspergilli - (Book / Chapter)
Moore, G.G., Beltz, S.B., Carbone, I., Ehrlich, K., Horn, B.W. 2011. The population dynamics of aflatoxigenic aspergilli. In: Guevara-Gonzalez, R.G., editor. Aflatoxins - Biochemistry and Molecular Biology. Rijeka, Croatia: Intech Open Access publishers. pp 347-366.
Aflatoxin biosynthetic pathway and pathway genes - (Book / Chapter)
Yu, J., Ehrlich, K. 2011. Aflatoxin biosynthetic pathway and pathway genes. In: Guevara-Gonzalez, R.G., editor. Aflatoxins - Biochemistry and Molecular Biology. Rijeka, Croatia: Intech Open Access publishers. pp 41-66.
Aspergillus flavus genetics and genomics in solving mycotoxin contamination of food and feed - (Book / Chapter)
Yu, J., Bhatnagar, D., Cleveland, T.E., Payne, G., Nierman, W.C., Bennett, J.W. 2012. Aspergillus flavus genetics and genomics in solving mycotoxin contamination of food and feed. In: Benkeblia, N. (ed). Omics Technologies: Tools for Food Science. CRC Press, Taylor & Francis Group, Boca Raton, FL. p. 367-402.
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