Chapter 18 : Genomics of Mycotoxin Production

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Food microbiologists often overlook the importance of fungi as a threat to food safety and security even though fungi produce a wide array of toxic compounds. is known to produce over 14 described mycotoxins. It is common for strains of to produce both aflatoxin and cyclopiazonic acid (CPA) and for commodities to contain both mycotoxins. Other than and , no other fungal genera are known to produce aflatrem; however, structurally related tremorgenic mycotoxins, such as penitrem from spp., are prevalent in other fungi and likely share common enzymes. Fungi have the capacity to produce many diverse secondary metabolites, and over 300 fungal secondary metabolites are described as mycotoxins. It is now possible to predict whether potential toxins produced by secondary metabolism clusters may be present in food. With respect to the regulation of aflatrem biosynthesis, researchers have shown that the gene called veA, previously shown to control aflatoxin and sclerotial production in was found to not only be necessary for the production of aflatoxins B and B and sclerotia, but also regulated the synthesis of the mycotoxins cyclopiazonic acid and aflatrem. New tools for genomewide gene profiling and functional analysis will surely reveal additional information on aflatoxin production and the regulation of the process. This knowledge will empower researchers to find effective strategies for controlling aflatoxin contamination of food and feed. Gradually, newly developed next-generation sequencing technologies will become common research tools for functional genomics studies.

Citation: Payne G, Georgianna D, Yu J, Ehrlich K, Obrian G, Bhatnagar D. 2011. Genomics of Mycotoxin Production, p 259-270. In Fratamico P, Liu Y, Kathariou S (ed), Genomes of Foodborne and Waterborne Pathogens. ASM Press, Washington, DC. doi: 10.1128/9781555816902.ch18
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1. Anderson, R. C. 2006. Evolution and origin of the Central Grassland of North America: climate, fire, and mammalian grazers. J. Torrey Bot. Soc. 133: 626647.
2. Antony, M.,, Y. Shukla, and, K. K. Janardhanan. 2003. Potential risk of acute hepatotoxicity of kodo poisoning due to exposure to cyclopiazonic acid. J. Ethnopharmacol. 87: 211214.
3. Bayram, O.,, S. Krappmann,, M. Ni,, J. W. Bok,, K. Helmstaedt,, O. Valerius,, S. Braus-Stromeyer,, N. J. Kwon,, N. P. Keller,, J. H. Yu, and, G. H. Braus. 2008. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science 320: 15041506.
4. Bennett, J. W., and, J. Arnold. 2001. Genomics for fungi, p. 267-297. In R. J. Howard and, N. A. R. Gow (ed.), The Mycota VIII, Biology of the Fungal Cell. Springer-Verlag, Heidelberg, Germany.
5. Bennett, J. W., and, M. Klich. 2003. Mycotoxins. Clin. Micro-biol. Rev. 16: 497516.
6. Bhatnagar, D.,, K. C. Ehrlich, and, T. E. Cleveland. 2003. Molecular genetic analysis and regulation of aflatoxin biosynthesis. Appl. Microbiol. Biotechnol. 61: 8393.
7. Blumenthal, C. Z. 2004. Production of toxic metabolites in Aspergillus niger, Aspergillus oryzae, and Trichoderma re-esei: justification of mycotoxin testing in food grade enzyme preparations derived from the three fungi. Regulatory Toxicol. Pharmacol. 39: 214228.
8. Bok, J. W., and, N. P. Keller. 2004. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot. Cell 3: 527535.
9. Bok, J. W.,, D. Noordermeer,, S. P. Kale, and, N. P. Keller. 2006. Secondary metabolic gene cluster silencing in Aspergillus nidu-lans. Mol. Microbiol. 61: 16361645.
10. Bouhired, S.,, M. Weber,, A. Kempf-Sontag,, N. P. Keller, and, D. Hoffmeister. 2007. Accurate prediction of the Aspergillus nid-ulans terrequinone gene cluster boundaries using the transcriptional regulator LaeA. Fungal Genet. Biol. 44: 11341145.
11. Boyd, M. L., and, P. J. Cotty. 2001. Aspergillus flavus and aflatoxin contamination of leguminous trees of the Sonoran Desert in Arizona. Phytopathology 91: 913919.
12. Bradburn, N.,, R. D. Coker, and, G. Blunden. 1994. The aetiology of Turkey “X” disease. Phytochemistry 35: 817.
13. Burdock, G. A.,, I. G. Carabin, and, M. G. Soni. 2001. Safety assessment of beta-nitropropionic acid: a monograph in support of an acceptable daily intake in humans. Food Chem. 75: 127.
14. Calvo, A. M.,, J. Bok,, W. Brooks, and, N. P. Keller. 2004. veA is required for toxin and sclerotial production in Aspergillus parasiticus. Appl. Environ. Microbiol. 70: 47334739.
15. Cary, J. W.,, G. R. Obrian,, D. M. Nielsen,, W. Nierman,, P. Harris-Coward,, J. Y. D. Bhatnagar,, T. E. Cleveland,, G. A. Payne, and, A. M. Calvo. 2007. Elucidation of veA-dependent genes associated with aflatoxin and sclerotial production in Aspergillus flavus by functional genomics. Appl. Microbiol. Biotechnol. 76: 11071118.
16. Chang, P. K. 2003. The Aspergillus parasiticus protein AFLJ interacts with the aflatoxin pathway-specific regulator AFLR. Mol. Gen. Genomics 268: 711719.
17. Chang, P. K.,, K. C. Ehrlich, and, S. S. Hua. 2006. Cladal re-latedness among Aspergillus oryzae isolates and Aspergillus flavus S and L morphotype isolates. Int. J. Food Microbiol. 108: 172177.
18. Chang, P. K., B. W. Horn, and, J. W. Dorner. 2009. Clustered genes involved in cyclopiazonic acid production are next to the aflatoxin biosynthesis gene cluster in Aspergillus flavus. Fungal Genet. Biol. 46: 176182.
19. Chang, P. K.,, B. W. Horn, and, J. W. Dorner. 2005. Sequence breakpoints in the aflatoxin biosynthesis gene cluster and flanking regions in nonaflatoxigenic Aspergillus flavus isolates. Fungal Genet. Biol. 42: 914923.
20. Chang, P. K.,, J. R. Wilkinson,, B. W. Horn,, J. Yu,, D. Bhatnagar, and, T. E. Cleveland. 2007. Genes differentially expressed by Aspergillus flavus strains after loss of aflatoxin production by serial transfers. Appl. Microbiol. Biotechnol. 77: 917925.
21. Chomeheon, P.,, S. Wiyakrutta,, N. Sriubolmas,, N. Ngamrojana-vanich,, D. Isarangkul, and, P. Kittakoop. 2005. 3-nitropropionic acid (3-NPA), a potent antimycobacterial agent from endo-phytic fungi: Is 3-NPA in some plants produced by endophytes? J. Nat. Products 68: 11031105.
22. Cleveland, T. E.,, J. J. Yu,, N. Fedorova,, D. Bhatnagar,, G. A. Payne,, W. C. Nierman, and, J. W. Bennett. 2009. Potential of Aspergillus flavus genomics for applications in biotechnology. Trends Biotechnol. 27: 151157.
23. Cole, R. J. 1986. Etiology of turkey X disease in retrospect: a case for the involvement of cyclopiazonic acid. Mycotoxin Res. 2: 37.
24. Cole, R. J., and, R. H. Cox. 1981. Sterigmatocystins, p. 67-72. In Handbook of Toxic Fungal Metabolites. Academic Press, New York, NY.
25. Cotty, P. J.,, P. Bayman,, D. S. Egel, and, K. S. Elias. 1994. Agriculture, aflatoxins, and aspergillus, p. 1-27. In The Genus Aspergillus: from Taxonomy and Genetics to Industrial Applications. FEMS Symposium No. 69. Plenum Press, New York, NY.
26. De Mello, F. R., and, V. M. Scussel. 2007. Characteristics of in-shell Brazil nuts and their relationship to aflatoxin contamination: criteria for sorting. J. Agric. Food Chem. 55: 9305.
27. Duran, R. M.,, J. W. Cary, and, A. M. Calvo. 2007. Production of cyclopiazonic acid, aflatrem, and aflatoxin by Aspergillus flavus is regulated by veA, a gene necessary for sclerotial formation. Appl. Microbiol. Biotechnol. 73: 11581168.
28. Ehrlich, K. C.,, J. W. Cary, and, B. G. Montalbano. 1999. Characterization of the promoter for the gene encoding the aflatoxin biosynthetic pathway regulatory protein AflR. Biochim. Et Biophys. Acta 1444: 412417.
29. Ehrlich, K. C.,, B. G. Montalbano, and, P. J. Cotty. 2007. Analysis of single nucleotide polymorphisms in three genes shows evidence for genetic isolation of certain Aspergillus flavus vegetative compatibility groups. FEMS Microbiol. Lett. 268: 231236.
30. El-Shanawany, A. A.,, M. E. Mostafa, and, A. Barakat. 2005. Fungal populations and mycotoxins in silage in Assiut and So-hag governorates in Egypt, with a special reference to characteristic Aspergilli toxins. Mycopathologia 159: 281289.
31. Fernandes, M.,, N. P. Keller, and, T. H. Adams. 1998. Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol. Microbiol. 28: 13551365.
32. Flaherty, J. E., and, G. A. Payne. 1997. Overexpression of aflR leads to upregulation of pathway gene transcription and increased aflatoxin production in Aspergillus flavus. Appl. Environ. Microbiol. 63: 39954000.
33. Fu, Y. X,, F. S. He,, S. L. Zhang, and, J. S. Zhang. 1995. Lipid-peroxidation in rats intoxicated with 3-nitropropionic acid. Toxicon 33: 327331.
34. Galagan, J. E.,, S. E. Calvo,, C. Cuomo,, L. J. Ma,, J. R. Wort-man,, S. Batzoglou,, S. I. Lee,, M. Basturkmen,, C. C. Spevak,, J. Clutterbuck,, V. Kapitonov,, J. Jurka,, C. Scaocchio,, M. Farman,, J. Butler,, S. Purcell,, S. Harris,, G. H. Braus,, O. Draht,, S. Busch,, C. D’Enfert,, C. Bouchier,, G. H. Goldman,, D. Bell-Pedersen,, S. Griffiths-Jones,, J. H. Doonan,, J. Yu,, K. Vienken,, A. Pain,, M. Freitag,, E. U. Selker,, D. B. Archer,, M. A. Penalva,, B. R. Oakley,, M. Momany,, T. Tanaka,, T. Kumagai,, K. Asai,, M. Machida,, W. C. Nierman,, D. W. Denning,, M. Caddick,, M. Hynes,, M. Paoletti,, R. Fischer,, B. Miller,, P. Dyer,, M. S. Sachs,, S. A. Osmani, and, B. W. Birren. 2005. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438: 11051115.
35. Gallagher, R. X,, J. L. Richard,, H. M. Stahr, and, R. J. Cole. 1978. Cyclopiazonic acid production by aflatoxigenic and non-aflatoxigenic strains of Aspergillus flavus. Mycopathologia 66: 3136.
36. Gallagher, R. X, and, B. J. Wilson. 1979. Aflatrem, the trem-orgenic mycotoxin from Aspergillus flavus. Mycopathologia 66: 183185.
37. Georgianna, D. R.,, N. Fedorova,, J. L. Burroughs,, A. L. Dolezal,, J. Bok,, S. Horowitz-Brown,, C. P. Woloshuk,, J. Yu,, N. Keller, and, G. Payne. 2010. Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters. Mol. Plant Pathol. 11: 213226.
38. Georgianna, D. R., and, G. A. Payne. 2008. Genetic regulation of aflatoxin biosynthesis: From gene to genome. Fungal Genet. Biol. 5: 5.
39. Gong, Y.,, A. Hounsa,, S. Egal,, P. C. Turner,, A. E. Sutcliffe,, A. J. Hall,, K. Cardwell, and, C. P. Wild. 2004. Postweaning exposure to aflatoxin results in impaired child growth: a longitudinal study in Benin, West Africa. Environ. Health Perspect. 112: 13341338.
40. Guzman, P. A., and, J. G. Sanchez. 1994. Characterization of telomeric regions from Ustilago-Maydis. Microbiology 140: 551557.
41. Hoffmeister, D., and, N. P. Keller. 2007. Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat. Prod. Rep. 24: 393416.
42. Horn, B. W. 2007. Biodiversity of Aspergillus section Flavi in the United States: a review. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 24: 10881101.
43. Horn, B. W. 2003. Ecology and population biology of aflatoxigenic fungi in soil. J. Toxicol. Toxin Rev. 22: 351379.
44. Horn, B. W., and, J. W. Dorner. 1999. Regional differences in production of aflatoxin B-1 and cyclopiazonic acid by soil isolates of Aspergillus flavus along a transect within the United States. Appl. Environ. Microbiol. 65: 14441449.
45. Horn, B. W., and, R. L. Greene. 1995. Vegitative compatibility within populations of Aspergillus flavus, Aspergillus parasiticus, and A. tamarii from a peanut field. Mycologia 87: 324332.
46. Horn, B. W.,, G. G. Moore, and, I. Carbone. 2009. Sexual reproduction in Aspergillus flavus. Mycologia 101: 423429.
47. Horn, B. W.,, J. H. Ramirez-Prado, and, I. Carbone. 2009. The sexual state of Aspergillus parasiticus. Mycologia 101: 275280.
48. Ito, Y.,, S. W. Peterson,, D. T. Wicklow, and, T. Goto. 2001. Aspergillus pseudotamarii, a new aflatoxin producing species in Aspergillus section Flavi. Mycol. Res. 105: 233239.
49. Janardhanan, K. K.,, A. Sattar, and, A. Husain. 1984. Production of fumigaclavine A by Aspergillus tamarii Kita. Can. J. Microbiol. 30: 247250.
50. Johnson, J. R.,, B. L. Robinson,, S. F. Ali, and, Z. Binienda. 2000. Dopamine toxicity following long term exposure to low doses of 3-nitropropionic acid (3-NPA) in rats. Toxicol. Lett. 116: 113118.
51. Kato, N.,, W. Brooks, and, A. M. Calvo. 2003. The expression of sterigmatocystin and penicillin genes in Aspergillus nidulans is controlled by veA, a gene required for sexual development. Eukaryot. Cell 2: 11781186.
52. Keller, N. P.,, G. Turner, and, J. W. Bennett. 2005. Fungal secondary metabolism—from biochemistry to genomics. Nat. Rev. Microbiol. 3: 937947.
53. Reference deleted.
54. Kim, J. H.,, B. C. Campbell,, J. J. Yu,, N. Mahoney,, K. L. Chan,, R. J. Molyneux,, D. Bhatnagar, and, T. E. Cleveland. 2005. Examination of fungal stress response genes using Saccharo-myces cerevisiae as a model system: targeting genes affecting aflatoxin biosynthesis by Aspergillus flavus Link. Appl. Microbiol. Biotechnol. 67: 807815.
55. Klich, M. A. 2002. Biogeography of Aspergillus species in soil and litter. Mycologia 94: 2127.
56. Lalitha Rao, B., and, A. Husain. 1985. Presence of cyclopiazonic acid in kodo millet (Paspalum scrobiculatum) causing ‘kodua poisoning’ in man and its production by associated fungi. Mycopathologia 89: 177180.
57. Larsen, T. O.,, J. Smedsgaard,, K. F. Nielsen,, M. A. Hansen,, R. A. Samson, and, J. C. Frisvad. 2007. Production of myco-toxins by Aspergillus lentulus and other medically important and closely related species in section Fumigati. Med. Mycol. 45: 225232.
58. Liot, G.,, B. Bossy,, S. Lubitz,, Y. Kushnareva,, N. Sejbuk, and, E. Bossy-Wetzel. 2009. Complex II inhibition by 3-NP causes mitochondrial fragmentation and neuronal cell death via an NMDA- and ROS-dependent pathway. Cell Death Differ. 16: 899909.
59. Luchowski, P.,, E. Luchowska,, W. A. Turski, and, E. M. Ur-banska. 2002. 1-methyl-4-phenylpyridinium and 3-nitropropionic acid diminish cortical synthesis of kynurenic acid via interference with kynurenine aminotransferases in rats. Neu-rosci. Lett. 330: 4952.
60. Machida, M.,, K. Asai,, M. Sano,, T. Tanaka,, T. Kumagai,, G. Terai,, K. Kusumoto,, T. Arima,, O. Akita,, Y. Kashiwagi,, K. Abe,, K. Gomi,, H. Horiuchi,, K. Kitamoto,, T. Kobayashi,, M. Takeuchi,, D. W. Denning,, J. E. Galagan,, W. C. Nierman,, J. Yu,, D. B. Archer,, J. W. Bennett,, D. Bhatnagar,, T. E. Cleveland,, N. D. Fedorova,, O. Gotoh,, H. Horikawa,, A. Hosoyama,, M. Ichinomiya,, R. Igarashi,, K. Iwashita,, P. R. Juvvadi,, M. Kato,, Y. Kato,, T. Kin,, A. Kokubun,, H. Maeda,, N. Maeyama,, J. Maruyama,, H. Nagasaki,, T. Nakajima,, K. Oda,, K. Okada,, I. Paulsen,, K. Sakamoto,, T. Sawano,, M. Takahashi,, K. Takase,, Y. Terabayashi,, J. R. Wortman,, O. Yamada,, Y. Yamagata,, H. Anazawa,, Y. Hata,, Y. Koide,, T. Komori,, Y. Koyama,, T. Minetoki,, S. Suharnan,, A. Tanaka,, K. Isono,, S. Kuhara,, N. Ogasawara, and, H. Kikuchi. 2005. Genome sequencing and analysis of Aspergillus oryzae. Nature 438: 11571161.
61. Magan, N., and, M. Olsen. 2004. Mycotoxins in Food: Detection and Control. Woodhead Publishing Ltd., Cambridge, United Kingdom.
62. Marsh, S. F., and, G. A. Payne. 1984. Preharvest infection of corn silks and kernels by Aspergillus flavus. Phytopathology 74: 12841289.
63. Marsh, S. F., and, G. A. Payne. 1984. Scanning EM studies on the colonization of dent corn by Aspergillus flavus. Phytopathology 74: 557561.
64. Martins, M. L., and, H. M. Martins. 1999. Natural and in vitro coproduction of cyclopiazonic acid and aflatoxins. J. Food Prot. 62: 292294.
65. Mellon, J. E., and, P. J. Cotty. 1995. Expression of elastinolytic activity among isolates in Aspergillus section Flavi. Myco-pathologia 131: 115120.
66. Mellon, J. E., and, P. J. Cotty. 2004. Expression of pectinase activity among Aspergillus flavus isolates from southwestern and southeastern United States. Mycopathologia 157: 333338.
67. Mellon, J. E.,, M. K. Dowd, and, P. J. Cotty. 2005. Substrate utilization by Aspergillus flavus in inoculated whole corn kernels and isolated tissues. J. Agric Food Chem. 53: 23512357.
68. Moncoq, K.,, C. A. Trieber, and, H. S. Young. 2007. The molecular basis for cyclopiazonic acid inhibition of the sarcoplasmic reticulum calcium pump. J. Biol. Chem. 282: 97489757.
69. Mooney, J. L.,, D. E. Hassett, and, L. N. Yager. 1990. Genetic analysis of suppressors of the veA1 mutation in Aspergillus nidulans. Genetics 126: 869874.
70. Nesbitt, B. F.,, J. O’Kelly,, K. Sargeant, and, A. Sheridan. 1962. Aspergillus flavus and turkey X disease. Toxic metabolites of Aspergillus flavus. Nature 195: 10621063.
71. Nicholson, M. J.,, A. Koulman,, B. J. Monahan,, B. L. Pritchard,, G. A. Payne, and, B. Scott. 2009. The genes for aflatrem biosynthesis in Aspergillus flavus and A. oryzae cluster at two different chromosomal loci. Appl. Environ. Microbiol. 75: 74697481.
72. Nierman, W. C.,, A. Pain,, M. J. Anderson,, J. R. Wortman,, H. S. Kim,, J. Arroyo,, M. Berriman,, K. Abe,, D. B. Archer,, C. Bermejo,, J. Bennett,, P. Bowyer,, D. Chen,, M. Collins,, R. Coulsen,, R. Davies,, P. S. Dyer,, M. Farman,, N. Fedorova,, T. V. Feldblyum,, R. Fischer,, N. Fosker,, A. Fraser,, J. L. Garcia,, M. J. Garcia,, A. Goble,, G. H. Goldman,, K. Gomi,, S. Griffith-Jones,, R. Gwilliam,, B. Haas,, H. Haas,, D. Harris,, H. Horiuchi,, J. Huang,, S. Humphray,, J. Jimenez,, N. Keller,, H. Khouri,, K. Ki-tamoto,, T. Kobayashi,, S. Konzack,, R. Kulkarni,, T. Kumagai,, A. Lafon,, J. P. Latge,, W. Li,, A. Lord,, C. Lu,, W. H. Majoros,, G. S. May,, B. L. Miller,, Y. Mohamoud,, M. Molina,, M. Monod,, I. Mouyna,, S. Mulligan,, L. Murphy,, S. O’Neil,, I. Paulsen,, M. A. Penalva,, M. Pertea,, C. Price,, B. L. Pritchard,, M. A. Quail,, E. Rabbinowitsch,, N. Rawlins,, M. A. Rajandream,, U. Reich-ard,, H. Renauld,, G. D. Robson,, S. Rodriguez de Cordoba,, J. M. Rodriguez-Pena,, C. M. Ronning,, S. Rutter,, S. L. Salzberg,, M. Sanchez,, J. C. Sanchez-Ferrero,, D. Saunders,, K. Seeger,, R. Squares,, S. Squares,, M. Takeuchi,, F. Tekaia,, G. Turner,, C. R. Vazquez de Aldana,, J. Weidman,, O. White,, J. Woodward,, J. H. Yu,, C. Fraser,, J. E. Galagan,, K. Asai,, M. Machida,, N. Hall,, B. Barrell, and, D. W. Denning. 2005. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438: 11511156.
73. Nishie, K.,, R. J. Cole, and, J. W. Dorner. 1985. Toxicity and neuropharmacology of cyclopiazonic acid. Food Chem. Toxicol. 23: 831839.
74. Nony, P. A.,, A. C. Scallet,, R. L. Rountree,, X. Ye, and, Z. Binienda. 1999. 3-nitropropionic acid (3-NPA) produces hypothermia and inhibits histochemical labeling of succinate dehydrogenase (SDH) in rat brain. Metabolic Brain Dis. 14: 8394.
75. O’Brian, G. R.,, A. M. Fakhoury, and, G. A. Payne. 2003. Identification of genes differentially expressed during aflatoxin biosynthesis in Aspergillus flavus and Aspergillus parasiticus. Fungal Genet. Biol. 39: 118127.
76. O’Brian, G. R.,, D. R. Georgianna,, J. R. Wilkinson,, J. Yu,, H. K. Abbas,, D. Bhatnagar,, T. E. Cleveland,, W. Nierman, and, G. A. Payne. 2007. The effect of elevated temperature on gene transcription and aflatoxin biosynthesis. Mycologia 99: 232239.
77. Osborne, C. P. 2008. Atmosphere, ecology and evolution: what drove the Miocene expansion of C–4 grasslands? J. Ecol. 96: 3545.
78. Payne, G. A. 1992. Aflatoxin in maize. Crit. Rev. Plant Sci. 10: 423440.
79. Payne, G. A.,, W. C. Nierman,, J. R. Wortman,, B. L. Pritchard,, D. Brown,, R. A. Dean,, D. Bhatnagar,, T. E. Cleveland,, M. Machida, and, J. Yu. 2006. Whole genome comparison of Aspergillus flavus and A. oryzae. Med. Mycol. 44: S9S11.
80. Payne, G. A.,, D. L. Thompson,, E. B. Lillehoj,, M. S. Zuber, and, C. R. Adkins. 1988. Effect of temperature on the prehar-vest infection of maize kernels by Aspergillus flavus. Phytopathology 78: 13761380.
81. Perrin, R. M.,, N. D. Fedorova,, J. W. Bok,, R. A. Cramer,, J. R. Wortman,, H. S. Kim,, W. C. Nierman, and, N. P. Keller. 2007. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PLoS Pathogens 3: 508517.
82. Pildain, M. B.,, J. C. Frisvad,, G. Vaamonde,, D. Cabral,, J. Varga, and, R. A. Samson. 2008. Two novel aflatoxin-produc-ing Aspergillus species from Argentinean peanuts. Int. J. Syst. Evol. Microbiol. 58: 725735.
83. Pildain, M. B.,, G. Vaamonde, and, D. Cabral. 2004. Analysis of population structure of Aspergillus flavus from peanut based on vegetative compatibility, geographic origin, mycotoxin and sclerotia production. Int. J. Food Microbiol. 93: 3140.
84. Polychronaki, N.,, R. M. West,, P. C. Turner,, H. Amra,, M. Abdel-Wahhab,, H. Mykkanen, and, H. El-Nezami. 2007. A longitudinal assessment of aflatoxin M1 excretion in breast milk of selected Egyptian mothers. Food Chem. Toxicol. 45: 12101215.
85. Price, M. S.,, S. B. Conners,, S. Tachdjian,, R. M. Kelly, and, G. A. Payne. 2005. Aflatoxin conducive and non-conducive growth conditions reveal new gene associations with aflatoxin production. Fungal Genet. Biol. 42: 506518.
86. Price, M. S.,, J. Yu,, W. C. Nierman,, H. S. Kim,, B. Pritchard,, D. Bhatnagar,, T. E. Cleveland, and, G. A. Payne. 2006. The aflatoxin pathway regulator AflR induces gene transcription inside and outside of the aflatoxin biosynthetic cluster. FEMS Microbiol. Lett. 255: 275279.
87. Rafiyuddin, M., N. J. Rao, S. Girisham, and, S. M. Reddy. 2006. Toxicology of tremorgenic mycotoxins on chicks. Natl. Acad. Sci. Lett. India 29: 311315.
88. Ramirez-Prado, J. H.,, G. G. Moore,, B. W. Horn, and, I. Car-bone. 2008. Characterization and population analysis of the mating-type genes in Aspergillus flavus and Aspergillus parasiticus. Fungal Genet. Biol. 45: 12921299.
89. Razzaghi-Abyaneh, M., M. Shams-Ghahfarokhi,, A. Allameh,, A. Kazeroon-Shiri,, S. Ranjbar-Bahadori, H. Mirzahoseini, and, M. B. Rezaee. 2006. A survey on distribution of Aspergillus section Flavi in corn field soils in Iran: population patterns based on aflatoxins, cyclopiazonic acid and sclerotia production. Mycopathologia 161: 183192.
90. Richard, J. L. 2008. Discovery of aflatoxins and significant historical features. Toxin Reviews 27: 171201.
91. Richard, J. L., and, G. A. Payne. 2003. Mycotoxins: Risks in Plant, Animal, and Human Systems 139. Council for Agricultural Science and Technology, Ames, IA.
92. Rokas, A. 2009. The effect of domestication on the fungal proteome. Trends Genet. 25: 6063.
93. Rokas, A.,, G. Payne,, N. D. Fedorova,, S. E. Baker,, M. Machida,, J. Yu,, D. R. Georgianna,, R. A. Dean,, D. Bhatnagar,, T. E. Cleveland,, J. R. Wortman,, R. Maiti,, V. Joardar,, P. Amedeo,, D. W. Denning, and, W. C. Nierman. 2007. What can comparative genomics tell us about species concepts in the genus Aspergillus? Stud. Mycol. 59: 1117.
94. Saikia, S.,, M. J. Nicholson,, C. Young,, E. J. Parker, and, B. Scott. 2008. The genetic basis for indole-diterpene chemical diversity in filamentous fungi. Mycol. Res. 112: 184199.
95. Saikia, S.,, M. J. Nicholson,, C. Young,, E. J. Parker, and, B. Scott. 2008. The genetic basis for indole-diterpenoid chemical diversity in filamentous fungi. Mycol. Res. 112: 184199.
96. Sanchez-Hervas, M.,, J. V. Gil,, F. Bisbal,, D. Ramon, and, P. V. Martinez-Culebras. 2008. Mycobiota and mycotoxin producing fungi from cocoa beans. Int. J. Food Microbiol. 125: 336340.
97. Scheidegger, K. A., and, G. A. Payne. 2003. Unlocking the secrets behind secondary metabolism: A review of Aspergillus flavus from pathogenicity to functional genomics. J. Toxicol. Toxin. Rev. 22: 423459.
98. Shwab, E. K.,, J. W. Bok,, M. Tribus,, J. Galehr,, S. Graessle, and, N. P. Keller. 2007. Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot. Cell. 6: 16561664.
99. Smetanina, O. F.,, T. A. Kuznetsova,, A. V. Gerasimenko,, A. I. Kalinovsky,, M. V. Pivkin,, P. C. Dmitrenok, and, G. B. Elyakov. 2004. Metabolites of the marine fungus Humicola fuscoatra KMM 4629. Russian Chemical Bulletin 53: 26432646.
100. Smith, C. A.,, C. P. Woloshuk,, D. Robertson, and, G. A. Payne. 2007. Silencing of the aflatoxin gene cluster in a dip-loid strain of Aspergillus flavus is suppressed by ectopic aflR expression. Genetics 176: 20772086.
101. Soler, F.,, F. Plenge-Tellechea,, I. Fortea, and, F. Fernandez-Belda. 1998. Cyclopiazonic acid effect on Ca2 +-dependent confor-mational states of the sarcoplasmic reticulum ATPase. Implication for the enzyme turnover. Biochemistry 37: 42664274.
102. Squire, R. A. 1981. Ranking animal carcinogens: a proposed regulatory approach. Science 214: 877880.
103. Stenske, K. A.,, J. R. Smith,, S. J. Newman,, L. B. Newman, and, C. A. Kirk. 2006. Aflatoxicosis in dogs and dealing with suspected contaminated commercial foods. J. Am. Vet. Med. Assoc. 228: 16861691.
104. Stinnett, S. M.,, E. A. Espeso,, L. Cobeno,, L. Araujo-Bazan, and, A. M. Calvo. 2007. Aspergillus nidulans VeA subcellular localization is dependent on the importin alpha carrier and on light. Mol. Microbiol. 63: 242255.
105. Tokuoka, M.,, Y. Seshime,, I. Fujii,, K. Kitamoto,, T. Takahashi, and, Y. Koyama. 2008. Identification of a novel polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) gene required for the biosynthesis of cyclopiazonic acid in Aspergillus oryzae. Fungal Genet. Biol. 45: 16081615.
106. Turner, P. C.,, A. C. Collinson,, Y. B. Cheung,, Y. Gong,, A. J. Hall,, A. M. Prentice, and, C. P. Wild. 2007. Aflatoxin exposure in utero causes growth faltering in Gambian infants. Int. J. Epidemiol. 36: 11191125.
107. Vaamonde, G.,, A. Patriarca,, V. F. Pinto,, R. Comerio, and, C. Degrossi. 2003. Variability of aflatoxin and cyclopiazonic acid production by Aspergillus section flavi from different substrates in Argentina. Int. J. Food Microbiol. 88: 7984.
108. Valdes, J. J.,, J. E. Cameron, and, R. J. Cole. 1985. Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects. Environ. Health Perspect. 62: 459463.
109. Venkatesh, P. K.,, S. Vairamuthu,, C. Balachandran,, B. M. Manohar, and, G. D. Raj. 2005. Induction of apoptosis by fungal culture materials containing cyclopiazonic acid and T-2 toxin in primary lymphoid organs of broiler chickens. Mycopathologia 159: 393400.
110. Vinokurova, N. G.,, N. E. Ivanushkina,, I. I. Khmel’nitskaia, and, M. U. Arinbasarov. 2007. Synthesis of alpha-cyclopiaz-onic acid by fungi of the genus Aspergillus. Prikl. Biokhim. Mikrobiol. 43: 486489.
111. Widiastuti, R.,, R. Maryam,, B. J. Blaney,, Salfina, and, D. R. Stoltz. 1988. Cyclopiazonic acid in combination with aflatoxins, zearalenone and ochratoxin A in Indonesian corn. Mycopathologia 104: 153156.
112. Widstrom, N. W.,, B. Z. Guo, and, D. M. Wilson. 2003. Integration of crop management and genetics for control of preharvest aflatoxin contamination of corn. J. Toxicol. Toxin Rev. 22: 195223.
113. Wilkinson, J. R.,, J. Yu,, H. K. Abbas,, B. E. Scheffler,, H. S. Kim,, W. C. Nierman,, D. Bhatnagar, and, T. E. Cleveland. 2007. Aflatoxin formation and gene expression in response to carbon source media shift in Aspergillus parasiticus. Food Addit. Contam. 24: 10511060.
114. Wilkinson, J. R.,, J. Yu,, J. M. Bland,, W. C. Nierman,, D. Bhatnagar, and, T. E. Cleveland. 2007. Amino acid supplementation reveals differential regulation of aflatoxin biosynthesis in Aspergillus flavus NRRL 3357 and Aspergillus parasiticus SRRC 143. Appl. Microbiol. Biotechnol. 74: 13081319.
115. Williams, J. H.,, T. D. Phillips,, P. E. Jolly,, J. K. Stiles,, C. M. Jolly, and, D. Aggarwal. 2004. Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am. J. Clin. Nutr. 80: 11061122.
116. Williams, R. B.,, J. C. Henrikson,, A. R. Hoover,, A. E. Lee, and, R. H. Cichewicz. 2008. Epigenetic remodeling of the fungal secondary metabolome. Org. Biomol. Chem. 6: 18951897.
117. Wilson, B. J., and, C. H. Wilson. 1964. Toxin from Aspergillus flavus: production on food materials of a substance causing tremors in mice. Science 144: 177178.
118. Woloshuk, C. P.,, K. R. Foutz,, J. F. Brewer,, D. Bhatnagar,, T. E. Cleveland, and, G. A. Payne. 1994. Molecular characterization of af lR, a regulatory locus for aflatoxin biosynthesis. Appl. Environ. Microbiol. 60: 24082414.
119. Wu, H. C.,, Q. Wang,, H. I. Yang,, H. Ahsan,, W. Y. Tsai,, L. Y. Wang,, S. Y. Chen,, C. J. Chen, and, R. M. Santella. 2008. Urinary 15-F-2t-isoprostane, aflatoxin B1 exposure and hepatitis B virus infection and hepatocellular carcinoma in Taiwan. Carcinogenesis 29: 971976.
120. Yin, Y.,, T. Lou,, L. Yan,, T. J. Michailides, and, Z. Ma. 2009. Molecular characterization of toxigenic and atoxigenic Aspergillus flavus isolates, collected from peanut fields in China. J. Appl. Microbiol. 107: 18571865.
121. Yu, J., D. Bha tnagar, and, T. E. Cleveland. 2004. Completed sequence of aflatoxin pathway gene cluster in Aspergillus parasiticus. FEBS Lett. 564: 126130.
122. Yu, J.,, P. -K. Chang,, K. C. Ehrlich,, J. W. Cary,, D. Bhatnagar,, T. E. Cleveland,, G. A. Payne,, J. E. Linz,, C. P. Woloshuk, and, J. W. Bennett. 2004. Clustered pathway genes in aflatoxin biosynthesis. Appl. Environ. Microbiol. 70: 12531262.
123. Yu, J., and, T. E. Cleveland. 2007. Aspergillus flavus genomics for discovering genes involved in aflatoxin biosynthesis, p. 246-260. In A. M. Rimando and, S. R. Baerson (ed.), Polyketides Biosynthesis, Biological Activity, and Genetic Engineering, vol. 955. American Chemical Society, Washington, DC.
124. Yu, J.,, C. M. Ronning,, J. R. Wilkinson,, B. C. Campbell,, G. A. Payne,, D. Bhatnagar,, T. E. Cleveland, and, W. C. Nierman. 2007. Gene profiling for studying the mechanism of aflatoxin biosynthesis in Aspergillus flavus and A. parasiticus. Food Addit. Contam. 24: 10351042.
125. Yu, J.,, C. A. Whitelaw,, W. C. Nierman,, D. Bhatnagar, and, T. E. Cleveland. 2004. Aspergillus flavus expressed sequence tags for identification of genes with putative roles in aflatoxin contamination of crops. FEMS Microbiol. Lett. 237: 333340.
126. Yu, J. J.,, G. A. Payne,, W. C. Nierman,, M. Machida,, J. W. Bennett,, B. C. Campbell,, J. F. Robens,, D. Bhatnagar,, R. A. Dean, and, T. E. Cleveland. 2008. Aspergillus flavus genomics as a tool for studying the mechanism of aflatoxin formation. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess. 25: 11521157.
127. Zhang, S.,, B. J. Monahan,, J. S. Tkacz, and, B. Scott. 2004. Indole-diterpene gene cluster from Aspergillus flavus. Appl. Environ. Microbiol. 70: 68756883.

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