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Aflatoxin Biosynthesis: Regulation and Subcellular Localization

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Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites

Part of the book series: Fungal Biology ((FUNGBIO))

Abstract

Aflatoxins are polyketide-derived secondary metabolites synthesized by specific Aspergillus species when they grow on a variety of susceptible plants, including economically important crops such as corn, cotton seed, peanuts, and tree nuts. Human aflatoxin exposure is strongly associated with liver and lung cancer, stunted growth, and immune suppression and these impacts generate strong pressure to reduce or eliminate aflatoxin contamination in food and feed. Initially, we provide a brief review of aflatoxin biosynthesis and toxicity. Then, we review how and where aflatoxin is synthesized in the mold and provide details of regulation of this process at the level of transcription and subcellular localization. We also explore the regulatory network that enables A. parasiticus to co-regulate diverse cellular functions including secondary metabolism, conidiospore development, and stress response. This review focuses significant attention on recent work from our laboratory but draws on the work of others to illustrate key concepts related to regulation of aflatoxin biosynthesis at the level of transcription and subcellular localization.

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Notes

  1. 1.

    Wee et al. (2014), in preparation.

  2. 2.

    Linz JE, Wee J, Roze LV Aspergillus parasiticus SU-1 genome sequence, predicted chromosome structure, and comparative gene expression under aflatoxin inducing conditions: Evidence that differential expression contributes to species phenotype. Euk Cell 2014;13:000.

  3. 3.

    Wee et al. (2014), in preparation.

  4. 4.

    Roze LV, Lavenieks M, Hong SY, Wee J, Wong SS, Vanos B, Awad D, Ehrlich K, Linz JE Aflatoxin biosynthesis is a novel source of reactive oxygen species – a potential redox mechanism to initiate resistance to oxidative stress.

  5. 5.

    Wee et al. (2014), in preparation.

  6. 6.

    Linz JE, Wee J, Roze LV Aspergillus parasiticus SU-1 genome sequence, predicted chromosome structure, and comparative gene expression under aflatoxin inducing conditions: Evidence that differential expression contributes to species phenotype. Euk Cell 2014;13:000.

References

  1. Liu Y, Chang CC, Marsh GM, Wu F. Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysis. Eur J Cancer. 2012;48:2125–36.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Liu Y, Wu F. Global burden of aflatoxin–induced hepatocellular carcinoma: a risk assessment. Environ Health Perspect. 2010;118:818–24.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Wagacha JM, Muthomi JW. Mycotoxin problem in Africa: current status, implications to food safety, and health and possible management strategies. Int J Food Microbiol. 2008;124:1–12.

    Article  CAS  PubMed  Google Scholar 

  4. CAST (Council for Agricultural Science and Technology) Task Force Report #139. Mycotoxins: Risks in plant, animal, and human systems. Ames, Iowa. 2003.

    Google Scholar 

  5. Cullen JM, Newberne PM. Experimental toxicology of aflatoxins. In: Eaton DL, Groopman JD, editors. The toxicology of aflatoxins: human health, veterinary, and agricultural significance. San Diego: Academic; 1994.

    Google Scholar 

  6. IARC (International Agency for Research on Cancer). Some herbal medicines, some mycotoxins, naphthalene, and styrene. Monogr Eval Carcinog Risks Hum. 2002;82:171–300.

    Google Scholar 

  7. Roebuck BD, Maxuitenko YY. Biochemical mechanisms and biological implications of the toxicity of aflatoxins are related to aflatoxin carcinogenesis. In: Eaton DL, Groopman JD, editors. The toxicology of aflatoxins. San Diego: Academic; 1994.

    Google Scholar 

  8. Wild CP, Gong YY. Mycotoxins and human disease: a largely ignored global health issue. Carcinogenesis. 2010;32:71–82.

    Article  CAS  Google Scholar 

  9. He XY, Tang L, Wang SL, Cai QS, Wang JS, Hong JY. Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract. Int J Cancer. 2006;118:2665–71.

    Article  CAS  PubMed  Google Scholar 

  10. Khlangwiset P, Shepard GS, Wu F. Aflatoxin and growth impairment: a review. Crit Rev Toxicol. 2011;41:740–55.

    Article  CAS  PubMed  Google Scholar 

  11. Wu F. Mycotoxin risk assessment for the purpose of setting international regulatory standards. Environ Sci Technol. 2004;38:4049–55.

    Article  CAS  PubMed  Google Scholar 

  12. Chulze SN. Strategies to reduce mycotoxin levels in maize during storage: a review. Food Addit Contam. 2010;27:651–7.

    Article  CAS  Google Scholar 

  13. Khlangwiset P, Wu F. Costs and efficacy of public health interventions to reduce aflatoxin-induced human disease. Food Addit Contam. 2010;27:998–1014.

    Article  CAS  Google Scholar 

  14. Wu F. Mycotoxin reduction in Bt corn: potential economic, health, and regulatory impacts. Transgenic Res. 2006;15:277–89.

    Article  PubMed  CAS  Google Scholar 

  15. Wu F, Khlangwiset P. Health economic impacts and cost effectiveness of aflatoxin—reduction in Africa: case studies in biocontrol and post-harvest interventions. Food Addit Contam. 2010;27:496–509.

    Article  CAS  Google Scholar 

  16. Wu F, Khlangwiset P. Evaluating the technical feasibility of aflatoxin risk reduction strategies in Africa. Food Addit Contam. 2010;27:658–76.

    Article  CAS  Google Scholar 

  17. Zahner H, Anke H, Anke T. Evolution and secondary pathways. In: Bennett JW, Ciegler A, editors. Secondary metabolism and differentiation in fungi, Mycology series, volume 5. New York: Marcel Dekker; 1983. p. 153–71. Chapter 6.

    Google Scholar 

  18. Rolfs M, Albert M, Keller NP, Kempken F. Secondary chemicals protect mould from fungivory. Biol Lett. 2007;3:523–5.

    Article  Google Scholar 

  19. Miller MJ, Linz JE. Genetic mechanisms involved in regulation of mycotoxin biosynthesis. In: Shetty K, editor. Food biotechnology. 2nd ed. Boca Raton: Taylor and Francis Group LLC; 2006.

    Google Scholar 

  20. Georgianna DR, Payne GA. Genetic regulation of aflatoxin biosynthesis: from gene to genome. Fungal Genet Biol. 2009;46:113–25.

    Article  CAS  PubMed  Google Scholar 

  21. Roze LV, Chanda A, Linz JE. Compartmentalization and molecular traffic in secondary metabolisms: a new understanding of established cellular processes. Fungal Genet Biol. 2011;48:35–48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Roze LV, Hong S-Y, Linz JE. Aflatoxin biosynthesis: current Frontiers. Annu Rev Food Sci Technol. 2013;4:293–311.

    Article  CAS  PubMed  Google Scholar 

  23. Yabe K, Nakajima H. Aflatoxin biosynthesis. Shokuhin Eiseigaku Zasshi. 2011;52:135–47. Japanese.

    Article  CAS  PubMed  Google Scholar 

  24. Georgianna DR, Fedorova ND, Burroughs JL, Dolezal AL, Bok JW, Horowitz-Brown S, Woloshuk CP, Yu J, Keller NP, Payne G. Beyond aflatoxin; four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters. Mol Plant Pathol. 2010;11:213–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Klionsky DJ, Herman PK, Emr SD. The fungal vacuole—composition, function, and biogenesis. Microbiol Rev. 1990;54:266–92.

    PubMed Central  CAS  PubMed  Google Scholar 

  26. Klionsky DJ. Nonclassical protein sorting to the yeast vacuole. J Biol Chem. 1998;273:10807–10.

    Article  CAS  PubMed  Google Scholar 

  27. Sarry JE, Chen S, Collum RP, Liang S, Peng M, Lang A, Naumann B, Dzierszinski F, Yuan C-X, Hippler M, Rea P. Analysis of the vacuolar luminal proteome of Saccharomyces cerevisiae. FEBS J. 2007;274:4287–305.

    Article  CAS  PubMed  Google Scholar 

  28. Wiederhold E, Gandhi T, Permentier HP, Breitling R, Poolman B, Slotboom DJ. The yeast vacuolar membrane proteome. Mol Cell Proteomics. 2009;8:380–92.

    Article  CAS  PubMed  Google Scholar 

  29. Cai H, Reinisch K, Ferro-Novik S. Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev Cell. 2007;12:671–82.

    Article  CAS  PubMed  Google Scholar 

  30. Oda M, Scott S, Hefner-Gravnik A, Caffarelli A, Klionsky DJ. Identification of a cytoplasm to vacuole targeting determinant in aminopeptidase I. J Cell Biol. 1996;132:999–1010.

    Article  CAS  PubMed  Google Scholar 

  31. Yorimitsu T, Klionsky DJ. Autophagy: molecular machinery for self-eating. Cell Death Differ. 2005;12:1542–52.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Pollack JK, Harris SD, Marten MR. Autophagy in filamentous fungi. Fungal Genet Biol. 2009;46:1–8.

    Article  CAS  PubMed  Google Scholar 

  33. Ohsumi K, Arioka M, Nakajima H, Kitamoto K. Cloning and characterization of a gene (avaA) from Aspergillus nidulans encoding a small GTPase involved in vacuolar biogenesis. Gene. 2002;291:77–84.

    Article  CAS  PubMed  Google Scholar 

  34. Lee LW, Chiou CH, Klomparens K, Cary JW, Linz JE. Sub-cellular localization of aflatoxin biosynthetic enzymes Nor-1, Ver-1, and OmtA in time-dependent fractionated colonies of Aspergillus parasiticus. Arch Microbiol. 2004;181:204–14.

    Article  CAS  PubMed  Google Scholar 

  35. Chanda A, Roze LV, Kang S, Artymovich KA, Hicks GR, Raikel N. A key role for vesicles in fungal secondary metabolism. Proc Natl Acad Sci U S A. 2009;106:19533–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Hong SY, Linz JE. Functional expression and sub-cellular localization of the aflatoxin pathway enzyme Ver-1 fused to enhanced green fluorescent protein. Appl Environ Microbiol. 2008;74:6385–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Hong SY, Linz JE. Functional expression and sub-cellular localization of the early aflatoxin pathway enzyme Nor-1 in Aspergillus parasiticus. Mycol Res. 2009;113:591–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Zouhar J, Hicks GR, Raikhel N. Sorting inhibitors (sortins): chemical compounds to study vacuolar sorting in Arabidopsis. Proc Natl Acad Sci U S A. 2004;101:9497–501.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Chiou CH, Lee LW, Owens SA, Whallon JH, Klomparens KL, Townsend CA, Linz JE. Distribution and sub-cellular localization of the aflatoxin enzyme versicolorin B synthase in time-fractionated colonies of Aspergillus parasiticus. Arch Microbiol. 2004;182:67–79.

    Article  CAS  PubMed  Google Scholar 

  40. Silva JC, Townsend CA. Heterologous expression, isolation, and characterization of versicolorin B synthase from Aspergillus parasiticus. A key enzyme in the aflatoxin B1 biosynthetic pathway. J Biol Chem. 1997;272:804–13.

    Article  CAS  PubMed  Google Scholar 

  41. Farkas T, Daugard M, Jaatela M. Identification of small molecule inhibitors of Phosphatidylinositol 3-kinase and autophagy. J Biol Chem. 2011;286:38904–12.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Park MR, Gupta MK, Lee HR, Das ZC, Uhm SJ, Lee HT. Possible involvement of Class III phosphatidylinositol-3-kinase in meiotic progression of porcine oocytes beyond germinal vesicle stage. Theriogenology. 2010;75:940–50.

    Article  PubMed  CAS  Google Scholar 

  43. Lindmo K, Stenmark H. Regulation of membrane traffic by phosphoinositide 3-kinases. J Cell Sci. 2005;119:605–14.

    Article  CAS  Google Scholar 

  44. Chanda A, Roze LV, Linz JE. Purification of a vesicle-vacuole (V) fraction from Aspergillus. Methods Mol Biol. 2012;944:259–66.

    CAS  PubMed  Google Scholar 

  45. Chanda A, Roze LV, Pastor A, Frame MK, Linz JE. Purification of a vesicle-vacuole fraction functionally linked to aflatoxin synthesis in Aspergillus parasiticus. J Microbiol Methods. 2009;78:28–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Linz JE, Chanda A, Whitten D, Roze LV. Proteomic and biochemical evidence support a role for membrane-bound, sub-cellular compartments in stress response and secondary metabolism in Aspergillus parasiticus. J Proteome Res. 2011;11:767–75.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  47. Chanda A, Roze LV, Linz JE. A possible role for exocytosis in aflatoxin export in Aspergillus parasiticus. Eukaryot Cell. 2010;9:1724–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  48. Menke J, Weber J, Broz K, Kistler HC. Cellular development associated with induced mycotoxin synthesis in the filamentous fungus fusarium graminearum. PLoS One. 2013;8(5):e63077.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Brodhagen M, Keller NP. Signaling pathways connecting mycotoxin production and sporulation. Mol Plant Pathol. 2006;7:285–301.

    Article  CAS  PubMed  Google Scholar 

  50. Roze LV, Beaudry RM, Keller NP, Linz JE. Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in Aspergillus parasiticus. Mycopathologia. 2004;158:219–32.

    Article  CAS  PubMed  Google Scholar 

  51. Abenza JF, Galindo A, Pantozopoulou A, Gil C, de los Rios V, Penalva MA. Aspergillus RabB (Rab5) integrates acquisition of degradative identity with the long distance movement of early endosomes. Mol Biol Cell. 2010;21:2756–69.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Slessareva JE, Rout SM, Temple B, Bankaitis VA, Dohlman HG. Activation of the phosphatidylinositol 3-kinase Vps34 by a G protein α subunit at the endosome. Cell. 2006;126: 191–203.

    Article  CAS  PubMed  Google Scholar 

  53. Ehrlich KC, Mack BM, Wei Q, Li P, Roze LV, Dazzo F, Cary JW, Bhatnagar D, Wee J, Linz JE. Association with AflR in endosomes reveals new functions for AflJ in aflatoxin biosynthesis. Toxins. 2012;4:1582–600.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Maggio-Hall LA, Wilson RA, Keller NP. Fundamental contribution of beta-oxidation to polyketide mycotoxin production in planta. Mol Plant Microbe Interact. 2005;18:783–93.

    Article  CAS  PubMed  Google Scholar 

  55. Hong SY, Roze LV, Wee J, Linz JE. Evidence that a transcription factor regulatory network coordinates oxidative stress response and secondary metabolism. MicrobiologyOpen. 2013;2:144–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Elahi MM, Kong Y-X, Matata BM. Oxidative stress as a mediator of cardiovascular disease. Oxid Med Cell Longev. 2009;2:259–69.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Jackson MJ, McArdle A. Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species. J Physiol. 2011;589:2139–45.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Janssen-Heininger YMW, Aesif SW, van der Velden J, Guala AS, Reiss JN, Roberson EC, Budd RC, Reynaert NL, Anathy V. Regulation of apoptosis through cysteine oxidation: implications for fibrotic lung disease. Ann N Y Acad Sci. 2010;1203:23–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Lee JL, Kim NY, Suh YA, Lee CH. Involvement of ROS in curcumin-induced autophagic cell death. Korean J Physiol Pharmacol. 2011;15:1–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  60. Lewis DFV. Review. Oxidative stress and the role of cytochromes P450 in oxygen activation. J Chem Technol Biotechnol. 2002;77:1095–100.

    Article  CAS  Google Scholar 

  61. Li X, Becker KA, Zhang Y. Ceramide in redox signalling and cardiovascular diseases. Cell Physiol Biochem. 2010;26:41–8.

    Article  PubMed  CAS  Google Scholar 

  62. Miaczymnski M, Bar-Sagi D. Signaling endosomes: seeing is believing. Curr Opin Cell Biol. 2010;22:535–40.

    Article  CAS  Google Scholar 

  63. Muro S, Cui X, Gajewski C, Murciano J-C, Muzykantov VR, Koval M. Intracellular trafficking of catalase nanoparticle targeted to ICAM-1 protects endothelial cells from oxidative stress. Am J Physiol Cell Physiol. 2003;285:C1339–47.

    Article  CAS  PubMed  Google Scholar 

  64. Ushio-Fukai M. Localizing NADPH oxidase-derived ROS. Sci Online. 2006; 349/re8: 1–8.

    Google Scholar 

  65. Ushio-Fukai M. Compartmentalization of redox signaling through NADPH oxidase-derived ROS. Antioxid Redox Signal. 2009;11:1289–99.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Roze LV, Chanda A, Laivenieks M, Wee J, Awad D, Linz JE. Stress-related transcription factor AtfB integrates secondary metabolism with oxidative stress response in Aspergilli. J Biol Chem. 2011;286:35137–48.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Shimizu K, Hicks JK, Huang T, Keller N. Pka, Ras and RGS protein interactions regulate activity of AflR, a Zn(II)Cys6 transcription factor in Aspergillus nidulans. Genetics. 2003;165:1095–104.

    PubMed Central  CAS  PubMed  Google Scholar 

  68. Bin W-B, Amaike S, Wohlback DJ, Gasch AP, Chiang YM, Wang CC, Bok J-W, Rohlfs M, Keller NP. An Aspergillus nidulans bZIP response pathway hardwired for defensive secondary metabolism operates through aflR. Mol Microbiol. 2012;83:1024–34.

    Article  CAS  Google Scholar 

  69. Shimizu K, Keller NP. Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics. 2001;157:591–600.

    PubMed Central  CAS  PubMed  Google Scholar 

  70. Tag A, Hicks J, Garifullina G, Ake CJ, Phillips TD, Beremand M, Keller N. G-protein signaling mediates differential production of toxic secondary metabolites. Mol Microbiol. 2000;38:658–65.

    Article  CAS  PubMed  Google Scholar 

  71. Lee JW, Roze LV, Linz JE. Evidence that a wortmannin-sensitive signal transduction pathway regulates aflatoxin biosynthesis. Mycologia. 2007;99:562–8.

    Article  CAS  PubMed  Google Scholar 

  72. Cebollero E, Reggiori F. Regulation of autophagy in yeast Saccharomyces cerevisiae. Biochim Biophys Acta. 2009;1793:1413–21.

    Article  CAS  PubMed  Google Scholar 

  73. McLean BA, Zhabyeyev P, Pituskin E, Paterson I, Haykowsky MJ, Oudit GY. PI3K inhibitors as novel cancer therapies. Implications for cardiovascular medicine. J Card Fail. 2013;19:268–82.

    Article  CAS  PubMed  Google Scholar 

  74. Kim EH, Suresh M. Role of PI3K/Akt signaling in memory CD8 T cell differentiation. Front Immunol. 2013;4:1–11.

    Google Scholar 

  75. Sprio DJ, Boll W, Kirchhausen T, Wessling-Resnick M. Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro. Mol Biol Cell. 1996;7:355–67.

    Article  Google Scholar 

  76. Wu YT, Tan HL, Shui G, Bauvy C, Huang Q, Wenk MR, Ong CN, Codongo P, Shen HM. Dual roles of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition of Class I and Class III phosphoinositide 3-kinase. J Biol Chem. 2010;285:10850–61.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Cary JW, Obrian GR, Nielsen DM, Nierman W, Harris-Coward P, Yu J, Bhatnagar D, Cleveland TE, Payne GA, Calvo AM. Elucidation of veA-dependent genes associated with aflatoxin and sclerotial production in Aspergillus flavus by functional genomics. Appl Microbiol Biotechnol. 2007;76:1107–18.

    Article  CAS  PubMed  Google Scholar 

  78. Calvo AM. The VeA regulatory system and its role in morphological and chemical development in fungi. Fungal Genet Biol. 2008;45:1053–61.

    Article  CAS  PubMed  Google Scholar 

  79. Bayram O, Krappman S, Ni M, Bok JW, Helmstaedt K, Valerius O, Braus-Stromeyer S, Kwon NJ, Keller NP, Yu JH, Braus G. VelB/VeA/LaeA complex coordinates light signal with fungal development and secondary metabolism. Science. 2008;320:1504–6.

    Article  CAS  PubMed  Google Scholar 

  80. Amaike S, Keller NP. Distinct roles for VeA and LaeA in development and pathogenesis of Aspergillus flavus. Eukaryot Cell. 2009;8:1051–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Adams TH, Deising H, Timberlake WE. brlA requires both zinc fingers to induce development. Mol Cell Biol. 1990;10:1815–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  82. Timberlake WE. Molecular genetics of Aspergillus development. Annu Rev Genet. 1990;24:5–36.

    Article  CAS  PubMed  Google Scholar 

  83. Burow GB, Gardner HW, Keller NP. A peanut seed lipoxygenase responsive to Aspergillus colonization. Plant Mol Biol. 2000;42:689–701.

    Article  CAS  PubMed  Google Scholar 

  84. Burow GB, Nesbitt TC, Dunlap J, Keller NP. Seed lipoxygenase products modulate Aspergillus mycotoxin biosynthesis. Mol Plant Microbe Interact. 1997;10:380–7.

    Article  CAS  Google Scholar 

  85. Calvo AM, Hinze LL, Gardner HW, Keller NP. Sporogenic effect of polyunsaturated fatty acids on development of Aspergillus spp. Appl Environ Microbiol. 1999;65:3668–73.

    PubMed Central  CAS  PubMed  Google Scholar 

  86. Tsitsiginis DI, Kowieski T, Zarnowski R, Keller NP. Three putative oxylipin biosynthetic genes integrate sexual and asexual development in Aspergillus nidulans. Microbiology. 2005;151:1809–21.

    Article  CAS  Google Scholar 

  87. Andrianopoulos A, Timberlake WE. The Aspergillus nidulans abaA gene encodes a transcriptional activator that acts as a genetic switch to control development. Mol Cell Biol. 1994;14:2503–15.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Sewall TC, Mims CW, Timberlake WE. Conidium differentiation in Aspergillus nidulans wild-type and wet-white (wetA) mutant strains. Dev Biol. 1990;138:499–508.

    Article  CAS  PubMed  Google Scholar 

  89. Roze LV, Miller MJ, Rarick M, Mahanti N, Linz JE. A novel cAMP-response element, CRE1, modulates expression of nor-1 in Aspergillus parasiticus. J Biol Chem. 2004;279:27428–39.

    Article  CAS  PubMed  Google Scholar 

  90. Hong SY, Roze L, Wee J, Linz JE. Evidence that a transcription factor regulatory network coordinates oxidative stress response and secondary metabolism in aspergilli. MicrobiologyOpen. 2012;2:144–60.

    Article  CAS  Google Scholar 

  91. Martinez-Pastor MT, Marchler G, Schuller C, Marchler-Bauer A, Ruis H, Estruch F. The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J. 1996;15:2227–35.

    PubMed Central  CAS  PubMed  Google Scholar 

  92. Chang PK, Scharfenstein LL, Luo M, Mahoney N, Molyneaux RJ, Yu J, Brown R, Campbell BC. Loss of msnA, a putative stress regulatory gene, in Aspergillus parasiticus and Aspergillus flavus increased production of conidia, aflatoxins, and kojic acid. Toxins. 2010;10:82–104.

    Google Scholar 

  93. Vargas-Perez I, Sanchez O, Kawasaki L, Georgellis D, Aguirre J. Response regulators SrrA and SskA are central components of a phosphorelay system involved in stress signal transduction and asexual sporulation in Aspergillus nidulans. Eukaryot Cell. 2007;6:1570–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Eshaghi M, Lee JH, Lei Z, Poon SY, Li J, Cho KH, Chu Z, Karaturi KM, Liu J. Genomic binding profile of the fission yeast stress-activated MAPK Sty1 and the bZIP transcriptional activator Atf1 in response to H2O2. PLoS One. 2010;5:e11620.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  95. Morgan BA, Banks GR, Toone WM, Raitt D, Kuge S, Johnston L. The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. EMBO J. 1997;16:1035–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Tian C, Li J, Glass NL. Exploring the bZIP transcription factor regulatory network in Neurospora crassa. Microbiology. 2010;157:747–59.

    Article  PubMed  CAS  Google Scholar 

  97. Hagiwara D, Asano Y, Yamashino T, Mizuno T. Characterization of bZip-type transcription factor AtfA with reference to stress responses of conidia of Aspergillus nidulans. Biosci Biotechnol Biochem. 2008;72:2756–60.

    Article  CAS  PubMed  Google Scholar 

  98. Reverberi M, Zjalic S, Ricelli A, Punelli F, Camera E, Fabbri C, Picardo M, Fanelli C, Fabbri AA. Modulation of antioxidant defense in Aspergillus parasiticus is involved in aflatoxin biosynthesis: a role for the ApyapA gene. Eukaryot Cell. 2008;7:988–1000.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Sakamoto K, Arima T, Kazuhiro I, Yamada O, Gomi K. Aspergillus oryzae atfB encodes a transcription factor required for stress tolerance in conidia. Fungal Genet Biol. 2008;45: 922–32.

    Article  CAS  PubMed  Google Scholar 

  100. Sakamoto K, Iwashita K, Yamada O, Kobayashi K, Mizuno A, Akita O, Mikami S, Shimoi H, Gomi K. Aspergillus oryzae atfA controls conidial germination and stress tolerance. Fungal Genet Biol. 2009;46:887–97.

    Article  CAS  PubMed  Google Scholar 

  101. Reverberi M, Zjalic S, Punelli F, Ricelli A, Fabbri AA, Fanelli C. Apyap1 affects aflatoxin biosynthesis during Aspergillus parasiticus growth in maize seeds. Food Addit Contam. 1994;24:1070–5.

    Article  CAS  Google Scholar 

  102. Reverberi M, Ricelli F, Zjalic S, Fabbri A, Fanelli C. Natural functions of mycotoxins and control of their biosynthesis in fungi. Appl Microbiol Biotechnol. 2010;87:899–911.

    Article  CAS  PubMed  Google Scholar 

  103. Jayashree T, Subramanyam C. Oxidative stress as a prerequisite for aflatoxin production by Aspergillus parasiticus. Free Radic Biol Med. 2000;29:981–5.

    Article  CAS  PubMed  Google Scholar 

  104. Kim JH, Yu J, Mahoney N, Chan KL, Molyneux RJ, Varga J, Bhatnagar D, Cleveland TE, Nierman WC, Campbell BC. Elucidation of the functional genomics of antioxidant-based inhibition of aflatoxin biosynthesis. Int J Food Microbiol. 2008;122:49–60.

    Article  CAS  PubMed  Google Scholar 

  105. Narasaiah KV, Sashidar RB, Subramanyam C. Biochemical analysis of oxidative stress in the production of aflatoxin and its precursor intermediates. Mycopathologia. 2006;162:179–89.

    Article  CAS  PubMed  Google Scholar 

  106. Roze LV, Calvo AM, Gunterus A, Beaudry R, Kall M, Linz JE. Ethylene modulates development and toxin biosynthesis in aspergillus possibly via an ethylene sensor-mediated signaling pathway. J Food Prot. 2004;67(3):438–47.

    CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Food Science and Human Nutrition, Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA

    John E. Linz

  2. Department of Food Science and Human Nutrition, Center for Integrative Toxicology, Michigan State University, East Lansing, MI, USA

    Josephine M. Wee

  3. Department of Plant Biology, Michigan State University, East Lansing, MI, USA

    Ludmila V. Roze

Authors
  1. John E. Linz
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  2. Josephine M. Wee
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  3. Ludmila V. Roze
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Corresponding author

Correspondence to John E. Linz .

Editor information

Editors and Affiliations

  1. Department of Molecular Biology, University of León, León, Spain

    Juan-Francisco Martín

  2. Parque Científico de León, Instituto de Biotecnología de León (INBIOTEC), León, Spain

    Carlos García-Estrada

  3. Institute of Chemical Engineering, Vienna University of Technology, Vienna, Austria

    Susanne Zeilinger

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© 2014 Springer Science+Business Media New York

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Linz, J.E., Wee, J.M., Roze, L.V. (2014). Aflatoxin Biosynthesis: Regulation and Subcellular Localization. In: Martín, JF., García-Estrada, C., Zeilinger, S. (eds) Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites. Fungal Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1191-2_5

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