Aflatoxin biosynthesis

Revista Iberoamericana de Micologia

Volumn 19, Issue 4, 2002, Pages 191-200

  Yu, Jiujiang ^a   Bhatnagar, Deepak ^a   Ehrlich, Kenneth C ^a  

^a SOUTHERN REGIONAL RESEARCH CENTER   (United States)

Author keywords

Aspergillus flavus; Aspergillus parasiticus; Gene cluster; Mycotoxins; Transcription factor

Indexed keywords

AFLATOXIN; CYTOCHROME P450; FATTY ACID SYNTHASE; FUNGAL ENZYME; METHYLTRANSFERASE; OXIDOREDUCTASE; POLYKETIDE SYNTHASE;

ASPERGILLUS FLAVUS; ASPERGILLUS PARASITICUS; BIOSYNTHESIS; FUNGAL GENETICS; GENE CLUSTER; GENE STRUCTURE; MOLECULAR BIOLOGY; NONHUMAN; REVIEW;

ASPERGILLUS; ASPERGILLUS FLAVUS; ASPERGILLUS PARASITICUS; FUNGI;

EID: 0036931348     PISSN: 11301406     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (175)

1. Cullen JM, Newberne PM. Acute hepatotoxicity of aflatoxins. In: Eaton DL, Groopman JD (Eds.) The toxicology of aflatoxins. New York, Academic Press, 1994: 3-26.
2. Goto T, Wicklow DT, Ito Y. Aflatoxin and cyclopiazonic acid production by sclerotium-producing Aspergillus tamarii strain. Appl Environ Microbiol 1996; 62: 4036-4038.
3. Peterson SW, Ito Y, Horn BW, Goto T. Aspergillus bombycis, a new aflatoxigenic species and genetic variation in its sibling species, A. nomius. Mycologia 2001; 93: 689-703.
4. Klich MA, Mullaney EJ, Daly CB, Cary JW. Molecular and physiological aspects of aflatoxin and sterigmatocystin biosynthesis by Aspergillus tamarii and A. ochraceoroseus. Appl Microbiol Biotechnol 2000; 53: 605-609.
5. Ito Y, Peterson SW, Wicklow DT, Goto T. Aspergillus pseudotamarii, a new aflatoxin-producing species in Aspergillus section Flavi. Mycol Res 2001; 105: 233-239.
6. Squire RA. Ranking animal carcinogens: a proposed regulatory approach. Science 1989; 214: 887-891.
7. Cleveland TE, Cary JW, Brown RL, et al. Use of biotechnology to eliminate aflatoxin in preharvest crops. Bull Inst Compr Agr Sci Kinki Univ 1997; 5: 75-90.
8. Bhatnagar D, Yu J, Ehrlich KC. Toxins of filamentous fungi. In: Breitenbach M, Crameri R, Lehrer S (Eds.) Fungal Allergy and Pathogenicity. Chem Immunol. Vol 81, Basel, Karger, 2002: 167-206.
9. nd Edition. New York, Marcel Dekker, 2003: in press.
10. Jelinek CF, Pohland AE, Wood GE. Worldwide occurrence of mycotoxins in foods and feeds - an update. J Assoc Off Anal Chem 1989; 72: 223-230.
11. Van Egmond HP. Current situation on regulations for mycotoxins: Overview of tolerances and status of standard methods of sampling and analysis. Food Addit Contam 1989; 6: 134-188.
12. Eaton DL, Groopman JD. The toxicology of aflatoxins-human health. Veterinary and agricultural significance. New York, Academic Press, 1994.
13. Hsu IC, Metcalf RA, Sun T, Welsh JA, Wang NJ, Harris CC. Mutational hot spot in the p53 gene in hepatocellular carcinomas. Nature (London) 1991; 350: 427-428.
14. Bressac B, Kew M, Wands J, Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from Southern Africa. Nature (London) 1991; 350: 429-431.
15. Groopman JD, Sabbioni G. Detection of aflatoxin and its metabolites in human biological fluids. In: Bray GA, Ryan DH (Eds.) Pennington Center Nutrition Series, Vol. 1. Mycotoxins, cancer and health. Baton Rouge, Louisiana State University Press, 1991: 18-31.
16. Wogan GN. Aflatoxins as risk factors for primary hepatocellular carcinoma in humans. In: Bray GA, Ryan DH (Eds.) Pennington Center Nutrition Series, Vol. 1. Mycotoxins, cancer and health. Baton Rouge, Louisiana State University Press, 1991; 3-17.
17. Yeh FS, Ju MC, Mo CC, et al. Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in Southern Guangxi, China. Cancer Res 1989; 49: 2506-2709.
18. Chen CJ, Wang LY, Lu SN, et al. Elevated aflatoxin exposure and increased risk of hepatocellular carcinoma. Hepatology 1996; 24: 38-42.
19. Chen CJ, Yu MW, Liaw YF, et al. Chronic hepatitis B carriers with null genotypes of glutathione S-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carcinoma. Am J Human Genetics 1996; 59: 128-134.
20. Bhatnagar D, Ehrlich KC, Cleveland TE. Oxidation-reduction reactions in biosynthesis of secondary metabolites. In: Bhatnagar D, Lillehoj EB, Arora DK (Eds.) Handbook of applied mycology: mycotoxins in ecological systems. New York, Marcel Dekker 1992; 255-286.
21. Dutton MF. Enzymes and aflatoxin biosynthesis. Microbiol Rev 1988; 52: 274-295.
22. Payne GA, Brown MP. Genetics and physiology of aflatoxin biosynthesis. Annu Rev Phytopathol 1998; 36: 329-362.
23. Minto RE, Townsend CA. Enzymology and molecular biology of aflatoxin biosynthesis. Chem Rev 1997; 97: 2537-2555.
24. Trail F, Mahanti N, Linz J. Molecular biology of aflatoxin biosynthesis. Microbiol 1995; 141: 755-765.
25. Bhatnagar D, Cleveland TE, Brown RL, Cary JW, Yu J, Chang PK. Preharvest aflatoxin contamination: elimination through biotechnology. Ecological agriculture and sustainable development. In: Dhaiiwal GS, Arora R, Randhawa NS, Dhawan AR (Eds.) Luhiana, Indian Ecological Society, 1998: 100-129.
26. Cary JW, Chang, PK, Bhatnagar D. Clustered metabolic pathway genes in filamentous fungi. In: Khachatourans GG, Arora DK (Eds.) Applied mycology and biotechnology, agriculture and food production. Amsterdam, Elsevier Science BV, 2001; 1:165-198.
27. Townsend CA. Progress towards a biosynthetic rationale of the aflatoxin pathway. Pure Appl Chem 1997; 58: 227-238.
28. 2 by Aspergillus parasiticus. Appl Environ Microbiol 1987; 53: 2804-2807.
29. McGuire SM, Brobst SW, Graybill TL, Pal K, Townsend CA. Partitioning of tetrahydro- and dihydrobisfuran formation in aflatoxin biosynthesis defined by cell-free and direct incorporation experiments. J Am Chem Soc 1989; 111: 8308-8309.
30. 2. Appl Environ Microbiol 1988; 54: 2101-2106.
31. Yabe K, Nakamura H, Ando Y, Terakado N, Nakajima H, Hamasaki T. Isolation and characterization of Aspergillus parasiticus mutants with impaired aflatoxin production by a novel tip culture method. Appl Environ Microbiol 1988; 54: 2096-2100.
32. 2. Agric Biol Chem 1991; 55:1907-1911.
33. Yabe K, Nakamura M, Hamasaki T. Enzymatic formation of G-group aflatoxins and biosynthetic relationship between G- and B-group aflatoxins. Appl Environ Microbiol 1999; 65: 3867-3872.
34. Bennett JW, Chang PK, Bhatnagar D. One gene to whole pathway: the role of norsolorinic acid in aflatoxin research. Adv Appl Microbiol 1997; 45: 1-15.
35. Chang PK, Yu J, Ehrlich KC, et al. The aflatoxin biosynthesis gene adhA in Aspergillus parasiticus is involved in conversion of 5′-hydroxyaverantin to averufin. Appl Environ Microbiol 2000; 66: 4715-4719.
36. Yabe K, Ando Y, Hamasaki T. A metabolic grid among versiconal hemiacetal acetate, versiconol acetate, versiconol and versiconal during aflatoxin biosynthesis. J Gen Microbiol 1991; 137: 2469-2475.
37. Yabe K, Matsuyama Y, Ando Y, Nakajima H, Hamasaki T. Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic acid to averufin. Appl Environ Microbiol 1993; 59: 2486-2492.
38. Yabe K, Hamasaki T. Stereochemistry during aflatoxin biosynthesis: cyclase reaction in the conversion of versiconal to versicolorin B and racemization of versiconal hemiacetal acetate. Appl Environ Microbiol 1993; 59: 2493-2500.
39. 1 biosynthesis strategies for identifying pertinent genes. Mycopathologia 1989; 107: 75-83.
40. 2 producing mutant of Aspergillus fiavus. FASEB J 1993; 7: A1234.
41. Bhatnagar D, Cleveland TE. Purification and characterization of a reductase from Aspergillus parasiticus SRRC 2043 involved in aflatoxin biosynthesis. FASEB J 1990; 4: A2164.
42. Hsieh DP, Wan CC, Billington JA. A versiconal hemiacetal acetate converting enzyme in aflatoxin biosynthesis. Mycopathologia 1989; 107: 121-126.
43. 2 a reductase activity in extracts from Aspergillus parasiticus. Mycopathologia 1990; 111: 39-45.
44. 1 biosynthesis. Bioorganic & Medicinal Chemistry Letters 1993; 3: 653-656.
45. Brown DW, Adams TH, Keller NP. Aspergillus has distinct fatty acid synthases for primary and secondary metabolism. Proc Natl Acad Sci USA 1996; 93: 14873-14877.
46. 2 biosynthesis. Biochem 1991; 30: 4343-4350.
47. Chuturgoon AA, Dutton MF, Berry RK. The preparation of an enzyme associated with aflatoxin biosynthesis by affinity chromatography. Biochem Biophys Res Comm 1990; 166: 38-42.
48. Yabe K, Ando Y, Hashimoto J, Hamasaki T. Two distinct O-methyltransferases in aflatoxin biosynthesis. Appl Environ Microbiol 1989; 55: 2172-2177.
49. Bhatnagar D, Ullah AHJ, Cleveland TE. Purification and characterization of a methyltransferase from Aspergillus parasiticus SRRC 163 involved in aflatoxin biosynthetic pathway. Prep Biochem 1988; 18: 321-349.
50. Keller NP, Dischinger JHC, Bhatnagar D, Cleveland TE, Ullah AHJ. Purification of a 40-kilodalton methyltransferase active in the aflatoxin biosynthetic pathway. Appl Environ Microbiol 1993; 59: 479-484.
51. Bhatnagar D, Lax AR, Prima B, Cary JW, Cleveland TE. Purification of a 43 Kda enzyme that catalyzes the reduction of norsolorinic acid to averantin in aflatoxin biosynthesis. FASEB J 1996; 10: A1522.
52. Lin BK, Anderson JA. Purification and properties of versiconal cyclase from Aspergillus parasiticus. Arch Biochem Biophys 1992; 293: 67-70.
53. Silva JC, Minto RE, Barry CE, Holland KA, Townsend CA. Isolation and characterization of the versicolorin B synthase gene from Aspergillus parasiticus: expansion of the aflatoxin B, biosynthetic cluster. J Biol Chem 1996; 271: 13600-13608.
54. Matsushima K, Ando Y, Hamasaki T, Yabe K. Purification and characterization of two versiconal hemiacetal acetate reductases involved in aflatoxin biosynthesis. Appl Environ Microbiol 1994; 60: 2561-2567.
55. Kusumoto K, Hsieh DP. Purification and characterization of the esterases involved in aflatoxin biosynthesis in Aspergillus parasiticus. Can J Microbiol 1996; 8: 804-810.
56. Chatterjee M, Townsend CA. Evidence for the probable final steps in aflatoxin biosynthesis. J Org Chem 1996; 59: 4424-4429.
57. Bhatnagar D, Cleveland TE. Aflatoxin biosynthesis: developments in chemistry, biochemistry and genetics. In: Shotwell OL, Hurburgh CR Jr, (Eds.). Aflatoxin in corn: New perspectives. Ames, Iowa State University Press, 1991: 391-405.
58. Bayman P, Cotty PJ. Vegetative compatibility and genetic diversity in the Aspergillus flavus population of a single field. Can J Bot 1991; 69: 1707-1711.
59. Bennett JW, Papa KE. The aflatoxigenic Aspergillus. In: Ingram DS, Williams PA (Eds.) Genetics of Plant Pathogenic Fungi. London, Academic 1988: 264-280.
60. Payne GA, Woloshuk CP. The transformation of Aspergillus flavus to study aflatoxin biosynthesis. Mycopathologia 1989; 107: 139-144.
61. Keller NP, Cleveland TE, Bhatnagar D. A molecular approach towards understanding aflatoxin production. In: Bhatnagar D, Liilehoj EB, Arora DK (Eds.). Mycotoxins in ecological systems Vol. 5. New York, Marcel Dekker Inc., 1992: 287-310.
62. Foutz KR, Woloshuk CP, Payne GA. Cloning and assignment of linkage group loci to a karyotypic map of the filamentous fungus Aspergillus flavus. Mycologia 1995; 87: 787-794.
63. Townsend CA, Christensen SB, Trautwein K. Hexanoate as a starter unit in polyketide synthesis. J Am Chem Soc 1984; 106: 3868-3869.
64. Trail F, Mahanti N, Rarick M, et al. Physical and transcriptional map of an aflatoxin gene cluster in Aspergillus parasiticus and functional disruption of a gene involved early in the aflatoxin pathway. Appl Environ Microbiol 1995; 61: 2665-2673.
65. Mahanti N, Bhatnagar D, Cary JW, Joubran J, Linz JE. Structure and function of fas-1A, a gene encoding a putative fatty acid synthetase directly involved in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 1996; 62: 191-195.
66. 1. Chem Biol 1996; 3: 463-469.
67. 1. Mol Gen Genet 1995; 248: 270-277.
68. Feng GH, Leonard TJ. Characterization of the polyketide synthase gene (pksLl) required for aflatoxin biosynthesis in Aspergillus parasiticus. J Bact 1995; 177: 6246-6254.
69. Bennett JW. Loss of norsolorinic acid and aflatoxin production by a mutant of Aspergillus parasiticus. J Gen Microbiol 1981; 124 : 429-432.
70. Vederas JC, Nakashima TT. Biosynthesis of averufin by Aspergillus parasiticus: detection of 180-1abel by 13C NMR isotope shifts. J Chem Soc Chem Commun 1980; 4: 183-185.
71. 1 precursor: placement in the biosynthetic pathway. Appl Environ Microbiol 1980; 39: 835-839.
72. Chang PK, Skory CD, Linz JE. Cloning of a gene associated with aflatoxin biosynthesis in Aspergillus parasiticus. Curr Genet 1991; 21: 231-233.
73. Trail F, Chang PK, Cary J, Linz JE. Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins by Aspergillus parasiticus. Appl Environ Microbiol 1994; 60: 4078-4085.
74. Cary JW, Wright M, Bhatnagar D, Lee R, Chu FS. Molecular characterization of an Aspergillus parasiticus dehydrogenase gene, norA, located on the aflatoxin biosynthesis gene cluster. Appl Environ Microbiol 1996; 62: 360-366.
75. Bennett JW, Bhatnagar D, Chang PK. The molecular genetics of aflatoxin biosynthesis. FEMS-Symp Madison, Wisconsin, Science Tech Publishers, 1994; 69 :51-58.
76. Yu J, Chang PK, Bhatnagar D, Cleveland TE. Cloning and functional expression of an esterase gene in Aspergillus parasiticus. Mycopathologia 2003; in press.
77. Yu J, Chang PK, Cary JW, Bhatnagar D, Cleveland TE. avnA, a gene encoding a cytochrome P-450 monooxygenase is involved in the conversion of averantin to averufin in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 1997; 63: 1349-1356.
78. Yu J, Woloshuk CP, Bhatnagar D, Cleveland TE. Cloning and characterization of avfA and omtB genes involved in aflatoxin biosynthesis in three Aspergillus species. Gene 2000; 248: 157-167.
79. Bennett JW, Lee LS, Cucullu AF. Effect of dichlorvos on aflatoxin and versicolorin A production in Aspergillus parasiticus. Bot Gaz 1976; 137: 318-324.
80. Skory CD, Chang PK, Cary J, Linz JE. Isolation and characterization of a gene from Aspergillus parasiticus associated with the conversion of versicolorin A to sterigmatocystin in aflatoxin biosynthesis. Appl Environ Microbiol 1992; 58: 3527-3537.
81. Silva JC, Townsend CA. Heterologous expression, isolation, and characterization of versicolorin B synthase from Aspergillus parasiticus. J Biol Chem 1996; 272: 804-813.
82. McGuire SM, Silva JC, Casillas EG, Townsend CA. Purification and characterization of versicolorin B synthase from Aspergillus parasiticus. Catalysis of the stereodifferentiating cyclization in aflatoxin biosynthesis essential to DNA interaction. Biochem 1996; 35: 11470-11486.
83. Kelkar HS, Hernant S, Skloss TW, Haw JF, Keller NP, Adams TH. Aspergillus nidulans stcL encodes a putative cytochrome P-450 monooxygenase required for bisfuran desaturation during aflatoxin/sterigmatocystin biosynthesis. J Biol Chem 1997; 272: 1589-1594.
84. 1 in late growth-phase Aspergillus parasiticus cultures. Appl Environ Microbiol 1987; 53: 1711-1713.
85. Yu J, Cary JW, Bhatnagar D, Cleveland TE, Keller NP, Chu FS. Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O-methyltransferase involved in aflatoxin biosynthesis. Appl Environ Microbiol 1993; 59: 3564-3571.
86. Yu J, Chang PK, Payne GA, Cary JW, Bhatnagar D, Cleveland TE. Comparison of the omtA genes encoding O-methyltransferases involved in aflatoxin biosynthesis from Aspergillus parasiticus and A. flavus. Gene 1995; 163: 121-125.
87. Motomura M, Chihaya N, Shinozawa T, Hamasaki T, Yabe K. Cloning and characterization of the O-methyltransferase I gene (dmtA) from Aspergillus parasiticus associated with the conversions of demethylsterigmatocystin to sterigmatocystin and dihydrodemethylsterigmatocystin to dihydrosterigmatocystin in aflatoxin biosynthesis. Appl Environ Microbiol 1999; 65: 4987-4994.
88. Prieto R, Woloshuk CP. ord1, an oxidoreductase gene responsible for conversion of O-methylsterigmatocystin to aflatoxin in Aspergillus flavus. Appl Environ Microbiol 1997; 63: 1661-1666.
89. 2 biosynthesis. Appl Environ Microbiol 1998; 64: 4834-4841.
90. Cleveland TE, Bhatnagar D. Molecular regulation of aflatoxin biosynthesis. In: Bray GA, Ryan DH (Eds.) Pennington Center Nutrition Series, Vol. 1. Mycotoxins, cancer and health. Baton Rouge, Louisiana State University Press, 1991: 270-287.
91. Yu J, Chang PK, Cary JW, et al. Comparative mapping of aflatoxin pathway gene clusters in Aspergillus parasiticus and Aspergillus flavus. Appl Environ Microbiol 1995; 61: 2365-2371.
92. Yu J, Chang PK, Bhatnagar D, Cleveland TE. Genes encoding cytochrome P450 and monooxigenase enzymes define one end of the aflatoxin pathway gene cluster in Aspergillus parasiticus. Appl Microbiol Biotechnol 2000; 53: 583-590.
93. Chang PK, Yu J. Characterization of a partial duplication of the aflatoxin gene cluster in Aspergillus parasiticus ATCC 56775. Appl Microbiol Biotechnol 2002; 58: 632-636.
94. Liang SH, Skory CD, Linz JE. Characterization of the function of the ver-1A and ver-1B genes, involved in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 1996; 62: 4568-4575.
95. Chiou CH, Miller M, Wilson DL, Trail F, Linz JE. Chromosomal location plays a role in regulation of aflatoxin gene expression in Aspergillus parasiticus. Appl Environ Microbiol 2002; 68: 306-315.
96. Brown DW, Yu JH, Kelkar HS, et al. Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. Proc Natl Acad Sci USA 1996; 93: 1418-1422.
97. Chang PK, Ehrlich KC, Yu J, Bhatnagar D, Cleveland TE. Increased expression of Aspergillus parasiticus aflR, encoding a sequence-specific DNA binding protein, relieves nitrate inhibition of aflatoxin biosynthesis. Appl Environ Microbiol 1995; 61: 2372-2377.
98. Yu JH, Butchko RA, Fernandes M, Keller NP, Leonard TJ, Adams TH. Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus. Curr Genet 1996; 29: 549-555.
99. Ehrlich KC, Montalbano BG, Bhatnagar D, Cleveland TE. Alteration of different domains in AFLR affects aflatoxin pathway metabolism in Aspergillus parasiticus transformants. Fungal Genet Biol 1998; 23: 279-287.
100. Keller NP, Hohn TM. Metabolic pathway gene clusters in filamentous fungi. Fungal Genet Biol 1997; 21: 17-29.
101. Proctor RH, Fusarium toxins: Trichothecenes and Fumonisins, In: Cary JW, Linz JE, Bhatnagar D (Eds.) Microbial Foodborne Diseases: Mechanisms of pathogenesis and toxin synthesis. Technomic, Lancaster, 2000: 363-381.
102. Trapp SC, Hohn TM, McCormick S, Jarvis BB. Characterization of the gene cluster for biosynthesis of macrocyclic trichothecenes in Myrothecium roridum. Mol Gen Genet 1998; 257: 421-432.
103. Kimura N, Tsuge T. Gene cluster involved in melanin biosynthesis of the filamentous fungus Alternaria alternata. J Bacteriol 1993; 175: 4427-4435.
104. Tsai HF, Wheeler MH, Chang YC, Kwon-Chung KJ. A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus. J Bacteriol 1999; 181: 6469-6477.
105. Proctor RH, Desjardins AE, Plattner RD. Biosynthetic and genetic relationships of B-series fumonisins produced by Gibberella fujikuroi mating population A. Nat Toxins 1999; 7: 251-258.
106. Ahn JH, Walton JD, Chromosomal organization of TOX2, a complex locus controlling host-selective toxin biosynthesis in Cochliobolus carbonum. Plant Cell 1996; 8: 887-897.
107. Tanaka A, Shiotani H, Yamamoto M, Tsuge T. Insertional mutagenesis and cloning of the genes required for biosynthesis of the host-specific AK-toxin in the Japanese pear pathotype of Alternaria alternata. Mol Plant Microbe Interact 1999; 12: 691-702.
108. Johnstone IL, McCabe PC, Greaves P, et al. Isolation and characterisation of the crnA-niiA-niaD gene cluster for nitrate assimilation in Aspergillus nidulans. Gene 1990; 90: 181-192.
109. Haas H, Marzluf GA. NRE, the major nitrogen regulatory protein of Penicillium chrysogenum, binds specifically to elements in the intergenic promoter regions of nitrate assimilation and penicillin biosynthetic gene clusters. Curr Genet 1995; 28: 177-183.
110. Kitamoto N, Kimura T, Kito Y, Ohmiya K, Tsukagoshi N. The nitrate reductase gene from a shoyu koji mold, Aspergillus oryzae KBN616. Biosci Biotechnol Biochem 1995; 9: 1795-1797.
111. Amaar YG, Moore MM. Mapping of the nitrate-assimilation gene cluster (crnA-niiA-niaD) and characterization of the nitrite reductase gene (niiA) in the opportunistic fungal pathogen Aspergillus fumigatus. Curr Genet 1998; 33: 206-215.
112. Chang PK, Ehrlich KC, Linz JE, Bhatnagar D, Cleveland TE, Bennett JW. Characterization of the Aspergillus niaD and niiA gene cluster. Curr Genet 1996; 30: 68-75.
113. Chang PK, Yu J, Bhatnagar D, Cleveland TE. Characterization of the Aspergillus parasiticus major nitrogen regulatory gene, areA. Biochim Biophys Acta 2000; 1491: 263-266.
114. Williams RS, Davis MA, Howlett BJ. The nitrate and nitrite reductase-encoding genes of Leptosphaeria maculans are closely linked and transcribed in the same direction. Gene 1995; 158: 153-154.
115. Banks GR, Shelton PA, Kanuga N, Holden DW, Spanos A. The Ustilago maydis nar 1 gene encoding nitrate reductase activity: sequence and transcriptional regulation. Gene. 1993; 131: 69-78.
116. Yu J, Chang PK, Bhatnagar D, Cleveland TE. Cloning of sugar utilization gene cluster in Aspergillus parasiticus. Biochim Biophys Acta 2000; 1493: 211-214.
117. Arst HN Jr, MacDonald DW. A gene cluster in Aspergillus nidulans with an internally located cis-acting regulatory region. Nature 1975; 254: 26-31.
118. MacCabe AP, Riach MB, Unkles SE, Kinghorn JR. The Aspergillus nidulans npeA locus consists of three contiguous genes required for penicillin biosynthesis. EMBO J 1990; 9: 279-287.
119. Weigel BJ, Burgett SG, Chen VJ, et al. Cloning and expression in Escherichia coli of isopenicillin N synthetase genes from Streptomyces lipmanii and Aspergillus nidulans. J Bacteriol 1988; 170: 3817-3826.
120. Walton JD. Horizontal gene transfer and the evolution of secondary metabolite gene clusters in fungi: an hypothesis. Fungal Genet Biol 2000; 30: 167-171.
121. Bennett JW, Rubin PL, Lee LS, Chen PN. Influence of trace elements and nitrogen sources on versicolorin production by a mutant strain of Aspergillus parasiticus. Mycopathotogia 1979; 69: 161-166.
122. Tag A, Hicks J, Garifullina G, Ake C, Phillips TD, Beremand M, Keller N. G-protein signalling mediates differential production of toxic secondary metabolites (In Process Citation). Mol Microbiol 2000; 38: 658-665.
123. Payne GA, Nystrom GJ, Bhatnagar D, Cleveland TE, Woloshuk CP. Cloning of the afl-2 gene involved in aflatoxin biosynthesis from Aspergillus flavus. Appl Environ Microbiol 1993; 59: 156-162.
124. Chang PK, Cary JW, Bhatnagar D, et al. Cloning of the Aspergillus parasiticus apa-2 gene associated with the regulation of aflatoxin biosynthesis. Appl Environ Microbiol 1993; 59: 3273-3279.
125. Chang PK, Yu J, Bhatnagar D, Cleveland TE. Repressor-AFLR interaction modulates aflatoxin biosynthesis in Aspergillus parasiticus. Mycopathologia 1999; 147: 105-112.
126. Woloshuk CP, Foutz KR, Brewer JF, Bhatnagar D, Cleveland TE, Payne GA. Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis. Appl Environ Microbiol 1994; 60: 2408-2414.
127. Lamb HK, Newton GH, Levett LJ, Cairns E, Roberts CF, Hawkins AR. The QUTA activator and QUTR repressor proteins of Aspergillus nidulans interact to regulate transcription of cluinate utilization pathway genes. Microbiol 1996; 142: 1477-1490.
128. Burger G, Strauss J, Scazzocchio C, Lang BF. nirA, the pathway-specific regulatory gene of nitrate assimilation in Aspergillus nidulans, encodes a putative GAL4-type zinc finger protein and contains four introns in highly conserved regions. Mol Cell Biol 1991; 11: 5746-5755.
129. Todd RB, Andrianopoulos A, Davis MA, Hynes MJ. FacB, the Aspergillus nidulans activator of acetate utilization genes, binds dissimilar DNA sequences. EMBO J 1998; 17: 2042-2054.
130. Suarez T, Oestreicher N, Penalva MA, Scazzocchio C. Molecular cloning of the ua Y regulatory gene of Aspergillus nidulans reveals a favoured region for DNA insertions. Mol Gen Genet 1991; 230: 369-375.
131. Kulmburg P, Sequeval D, Lenouvel F, Mathieu M, Felenbok B. Identification of the promoter region involved in autoregulation of the transcriptional activator ALCR in Aspergillus nidulans. Mol Cell Biol 1992; 12: 1932-1939.
132. Chang PK, Yu J, Bhatnagar D, Cleveland TE. The carboxy-terminal portion of the aflatoxin pathway regulatory protein AFLR of Aspergillus parasiticus activates GAL 1.-lacZgene expression in Saccharomyces cerevisae. Appl Environ Microbiol 1999; 65: 2508-2512.
133. Matsushima K, Chang PK, Yu J, Abe K, Bhatnagar D, Cleveland TE. Pre-termination in aflR of Aspergillus sojae inhibits aflatoxin biosynthesis. Appl Microbiol Biotechnol 2001; 55: 585-589.
134. Matsushima K, Yashiro K, Hanya Y, Abe K, Yabe K, Hamasaki T. Absence of aflatoxin biosynthesis in koji mold (Aspergillus sofae). Appl Microbiol Biotechnol 2001; 55: 771-776.
135. Takahashi T, Chang PK, Matsushima K, et al. Non-functionality of Aspergillus sojae aflR in a strain of Aspergillus parasiticus with a disrupted aflR gene. Appl Environ Microbiol 2002: 68: 3737-3743.
136. Reece RJ, Ptashne M. Determinants of binding-site specificity among yeast C6 zinc cluster proteins. Science 1993; 261: 909-911.
137. Fernandes M, Keller NP, Adams TH. Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol Microbiol 1998; 28: 1355-1365.
138. Ehrlich KC, Montalbano BG. Binding of an aflatoxin biosynthesis regulatory protein to the 5'-upstream promoter region of several aflatoxin pathway genes. FASEB J 1995; 9: A1415.
139. Cary JW, Montalbano BG, Ehrlich KC. Promoter elements involved in the expression of the Aspergillus parasiticus aflatoxin biosynthesis pathway gene avnA. Biochim Biophys Acta 2000; 1491: 7-12.
140. Ehrlich KC, Montalbano BG, Cary JW. Binding of the C6-zinc cluster protein, AFLR, to the promoters of aflatoxin pathway biosynthesis genes in Aspergillus parasiticus. Gene 1999; 230: 249-257.
141. Ehrlich KC, Cary JW, Montalbano BG. Characterization of the promoter for the gene encoding the aflatoxin biosynthetic pathway regulatory protein AFLR. Biochim Biophys Acta 1999; 1444: 412-417.
142. Hicks JK, Yu JH, Keller NP, Adams TH. Aspergillus sporulation and mycotoxin production both require inactivation of the FadA G alpha protein-dependent signaling pathway. EMBO J 1997; 16: 4916-4923.
143. Tilburn J, Sarkar S, Widdick DA, et al. The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid-and alkaline expressed genes by ambient pH. EMBO J 1995; 14: 779-790.
144. Cotty PJ. Aflatoxin and sclerotial production by Aspergillus flavus: influence of pH. Phytopathology 1988; 78: 1250-1253.
145. Meyers DM, Obrian G, Du WL, Bhatnagar D, Payne GA. Characterization of aflJ, a gene required for conversion of pathway intermediates to aflatoxin. Appl Environ Microbiol 1998, 64: 3713-3717.
146. Flaherty JE, Payne GA. Overexpression of aflR leads to upregulation of pathway gene expression and increased aflatoxin production in Aspergillus flavus. Appl Environ Microbiol 1997; 63: 3995-4000.
147. Ehrlich K, Cotty PJ. Variability in nitrogen regulation of aflatoxin production by Aspergillus flavus strains. Appl Microbiol Biotechnol 2002; 60: 174-178.
148. Ehrlich KC, Montalbano BG, Cotty PJ. Sequence comparison of aflR from different Aspergillus species provides evidence for variability in regulation of aflatoxin production. Fungal Genet Biol 2003; in press.
149. Exley GE, Colandene JD, Garrett RH. Molecular cloning, characterization, and nucleotide sequence of nit-6, the structural gene for nitrate reductase in Neurospora crassa. J Bacteriol 1993; 175: 2379-2392.
150. Fu YH, Marzluf GA. Metabolic control and autoregulation of nit3, the nitrate reductase structural gene of Neurospora crassa. J Bacteriol 1988; 107: 657-661.
151. Kudla B, Caddick M, Langdon T, et al. The regulatory gene area mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J 1990; 9: 1355-1364.
152. Niehaus WG Jr, Jiang W. Nitrate induces enzymes of the marmitol cycle and suppresses versicolorin synthesis in Aspergillus parasiticus. Mycopathologia 1989; 107: 131-137.
153. Kachholz T, Demain AL. Nitrate repression of averufin and aflatoxin biosynthesis. J Nat Prod 1983; 46: 499-506.
154. Orvehed M, Haggblom P, Soderhall K. Nitrogen inhibition of mycotoxin production by Alternaria alternata. Appl Environ Microbiol 1988; 54: 2361-2364.
155. Ozcan S, Leong T, Johnston M. Rg11p of Saccharomyces cerevisiae, a key regulator of glucose-induced genes, is both an activator and a repressor of transcription. Molec Cell Biol 1996; 16: 6419-6426.
156. Muro-Pasteur MI, Gonzalez R, Strauss J, Narendja F, Scazzocchio C. The GATA factor AreA is essential for chromatin remodelling in a eukaryotic bidirectional promoter. EMBO J 1999; 18: 1584-1597.
157. Daniel PB, Walker WH, Habener JF. Cyclic AMP signaling and gene regulation. Annu Rev Nutr 1998; 18: 353-383.
158. Calvo AM, Wilson RA, Bok JW, Keller NP. Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev 2002; 66: 447-459.
159. Bu'Lock JD. Intermediary metabolism and antibiotic synthesis. Adv Appl Microbiol 1961; 3: 293-342.
160. Sekiguchi J, Gaucher GM. Conidiogenesis and secondary metabolism in Penicillium urticae. Appl Environ Microbiol 1977; 33:147-158.
161. 1 under the influence of conidiogenesis affecting compounds. Arch Microbiol 1982; 133: 236-238.
162. Guzman-de-Pena D, Aguirre J, Ruiz-Herrera J. Correlation between the regulation of sterigmatocystin biosynthesis and asexual and sexual sporulation in Emericella nidulans. Antonie Leeuwenhock 1998; 73: 199-205.
163. 1 biosynthesis and conidiation in Fusarium verticillioides by acyclin-like (C-type) gene, FCC1. Appl Environ Microbiol 2001; 67: 1607-1612.
164. Bennett JW, Leong PM, Kruger S, Keyes D. Sclerotial and low aflatoxigenic morphological variants from haploid and diploid Aspergillus parasiticus. Experientia 1986; 42: 841-851.
165. Kale SP, Bhatnagar D, Bennett JW. Isolation and characterization of morphological variants of Aspergillus parasiticus deficient in secondary metabolite production. Mycol Res 1994; 98: 645-652.
166. Kate SP, Cary JW, Bhatnagar D, Bennett JW. Characterization of experimentally induced, nonaflatoxingenic variant strains of Aspergillus parasiticus. Appl Environ Microbiol 1996; 62: 3399-3404.
167. Chang PK, Bennett JW, Cotty PJ. Association of aflatoxin biosynthesis and sclerotial development in Aspergillus parasiticus. Mycopathologia 2001; 153: 41-48.
168. Khan SN, Venkitasubramanian TA, Regulation of aflatoxin biosynthesis: effect of adenine nucleotides, cyclic AMP and N6-O2' -dibutyryl cyclic AMP on the incorporation of (1- 14C)-acetate into aflatoxins by Aspergillus parasiticus NRRL-3240. J Environ Sci Health (B) 1986; 21: 67-85.
169. Khan SN, Venkitasubramanian TA. Cyclic AMP pool and aflatoxin
170. Tamame M, Antequera F, Villanueva JR, Santos T. High frequency conversion of a "fluffy" developmental phenotype in Aspergillus spp. by 5-azacytidine treatment: evidence for involvement of a single nuclear gene. Mol Cell Biol 1983; 3: 2287-2297.
171. Wieser J, Lee BN, Fondon JW, Adams TH. Genetic requirement for initiating asexual development in Aspergillus nidulans. Curr Genet 1994; 27: 62-69.
172. Clutterbuck AJ. A mutational analysis of conidial development in Aspergillus nidulans. Genetics 1969; 63: 317-327.
173. Johnstone IL, Hughes SG, Clutterbuck AJ. Cloning an Aspergillus developmental gene by transformation. EMBO J 1985; 4: 1307-1311.
174. Yu JH, Weiser J, Adams TH. The Aspergillus FIbA RGS domain protein antagonizes G-protein signaling to block proliferation and allow development. EMBO J 1996; 15: 5184-5190.
175. Shimizu K, Keller NP. Genetic involvement of camp-dependent protein kinase in a G-protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics 2001; 157: 591-600.