Abstract
Aflatoxins, produced by some Aspergillus species, are toxic and extremely carcinogenic furanocoumarins. Recent investigations of the molecular mechanism of AFB biosynthesis showed that the genes required for biosynthesis are in a 70 kb gene cluster. They encode a DNA-binding protein functioning in aflatoxin pathway gene regulation, and other enzymes such as cytochrome P450-type monooxygenases, dehydrogenases, methyltransferases, and polyketide and fatty acid synthases. Information gained from these studies has led to a better understanding of aflatoxin biosynthesis by these fungi. The characterization of genes involved in aflatoxin formation affords the opportunity to examine the mechanism of molecular regulation of the aflatoxin biosynthetic pathway, particularly during the interaction between aflatoxin-producing fungi and plants.
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References
Bennett JW, Christiansen SB (1983) New perpectives on aflatoxin biosynthesis. Adv Appl Microbiol 29:53–92
Bennett JW, Fernholz FA, Lee LS (1978) Effect of light on aflatoxins, anthraquinones, and sclerotia in Aspergillus flavus and A. parasiticus. Mycologia 70:104–116
Bennett JW, Horowitz PC, Lee LS (1979) Production of sclerotia by aflatoxigenic and nonaflatoxigenic strains of Aspergillus flavus and A. parasiticus. Mycologia 71:415–422
Beppu T (1992) Secondary metabolites as chemical signals for cellular differentiation. Gene 115:159–165
Bhatnagar D, Ullah AH, Cleveland TE (1988) Purification and characterization of a methyltransferase from Aspergillus parasiticus SRRC 163 involved in aflatoxin biosynthetic pathway. Prep Biochem 18:321–349
Bhatnagar D, Ehrlich KC, Cleveland TE (1992) Oxidation-reduction reactions in biosynthesis of secondary metabolites. In: Bhatnagar D, Lillehoj EB, Arora DK (eds) Handbook of applied mycology, vol V. Mycotoxins in ecological systems. Dekker, New York, pp 255–285
Bhatnagar D, Chang P-K, Yu J, Ehrlich KC, Cleveland TE (1999) Molecular basis for environmental effects on aflatoxin production. In: Robens JF (ed) Proceedings of the Aflatoxin Elimination Workshop: 25–27 October 1999, St Louis, Mo. USDA Agricultural Research Service, Beltsville, Md., pp 29–30
Bhatnagar D, Cotty PJ, Cleveland TE (2000) Genetic and biological control of aflatoxigenic fungi. In: Wilson CL, Droby S (eds) Microbial food contamination. CRC Press, Boca Raton, Fla., pp 208–240
Bradshaw RE, Bhatnagar D, Ganley RJ, Gillman CJ, Monahan BJ, Seconi JM (2002) Dothistroma pini, a forest pathogen, contains homologs of aflatoxin biosynthetic pathway genes. Appl Environ Microbiol 68:2885–2892
Brown DW, Yu JH, Kelkar HS, Fernandes M, Nesbitt TC, Kellar NP, Adams TH, Leonard TL (1996) Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. Proc Natl Acad Sci USA 93:1418–1422
Bu'lock JD (1965) The biosynthesis of natural products. McGraw-Hill, New York
Burger G, Strauss J, Scazzocchio C, Lang B (1991) nirA, the pathway specific regulatory gene of nitrate assimilation in Aspergillus nidulans encodes a putative GAL4-type zinc finger protein and contains introns in highly conserved regions. Mol Cell Biol 11:5746–5755
Cary JW, Bhatnagar D (1995) Nucleotide sequence of an Aspergillus parasiticus gene strongly repressed by thiamine. Biochim Biophys Acta 1261:319–320
Cary JW, Wright M, Bhatnagar D, Lee R, Chu FS (1996) Molecular characterization of an Aspergillus parasiticus gene, norA, located on the aflatoxin biosynthesis gene cluster. Appl Environ Microbiol 62:360–366
Cary JW, Linz JE, Bhatnagar D (2000a) Aflatoxins: biological significance and regulation of biosynthesis. In: Cary JW, Linz JE, Bhatnagar D (eds) Microbial foodborne diseases: mechanisms of pathogenesis and toxin synthesis. Technomic, Lancaster, Pa., pp 317–361
Cary JW, Montalbano BG, Ehrlich KC (2000b) Promoter elements involved in the expression of the Aspergillus parasiticus aflatoxin biosynthesis pathway gene avnA. Biochim Biophys Acta 1491:7–12
Cary JW, Dyer JM, Ehrlich KC, Wright MS, Liang S-H, Linz JE (2002) Molecular characterization of a second copy of the aflatoxin regulatory gene, aflR-2 from Aspergillus parasiticus is non-functional. Biochim Biophys Acta 1576:316–323
Chang P-K, Yu J (2002) Characterization of a partial duplication of the aflatoxin gene cluster in Aspergillus parasiticus ATCC 56775. Appl Microbiol Biotechnol 58:632–636
Chang P-K, Skory CD, Linz JE (1992) Cloning of a gene associated with aflatoxin B1 biosynthesis in Aspergillus parasiticus. Curr Genet 21:231–233
Chang P-K, Cary JW, Bhatnagar D, Cleveland TE, Bennett JW, Linz JE, Woloshuk CP, Payne GA (1993) Cloning of the Aspergillus parasiticus apa-2 gene associated with the regulation of aflatoxin biosynthesis. Appl Environ Microbiol 59:3273–3279
Chang P-K, Bhatnagar D, Cleveland TE, Bennett JW (1995a) Sequence variability in homologs of the aflatoxin pathway gene aflR distinguishes species in Aspergillus section Flavi. Appl Environ Microbiol 61:40–43
Chang P-K, Cary JW, Yu J, Bhatnagar D, Cleveland TE (1995b) The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis. Mol Gen Genet 248:270–277
Chang P-K, Ehrlich KC, Yu J, Bhatnagar D, Cleveland TE (1995c) Increased expression of Aspergillus parasiticus aflR, encoding a sequence-specific DNA-binding protein, relieves nitrate inhibition of aflatoxin biosynthesis. Appl Environ Microbiol 61:2372–2377
Chang P-K, Yu J, Bhatnagar D, Cleveland TE (1999a) The carboxy-terminal portion of the aflatoxin pathway regulatory protein AFLR of Aspergillus parasiticus activates GAL1::lacZ gene expression in Saccharomyces cerevisiae. Appl Environ Microbiol 65:2508–2512
Chang P-K, Yu J, Bhatnagar D, Cleveland TE (1999b) Repressor-AFLR interaction modulates aflatoxin biosynthesis in Aspergillus parasiticus. Mycopathologia 147:105–112
Chang P-K, Yu J, Bhatnagar D, Cleveland TE (2000a) Characterization of the Aspergillus parasiticus major nitrogen regulatory gene, areA. Biochim Biophys Acta 1491:263–266
Chang P-K, Yu J, Ehrlich KC, Boue SM, Montalbano BG, Bhatnagar D, Cleveland TE (2000b) adhA in Aspergillus parasiticus is involved in the conversion of 5′-hydroxyaverantin to averufin. Appl Environ Microbiol 66:4715–4719
Ciegler A (1983) Evolution, ecology, and mycotoxins: some musings. In: Bennett JW, Ciegler A (eds) Secondary metabolism and differentiation in fungi. Dekker, New York, pp 429–439
Cole RJ, Cox EH (1987) Handbook of toxic fungal metabolites. Academic Press, New York
Cotty P (1988) Aflatoxin and sclerotial production by Aspergillus flavus: influence of pH. Phytopathology 78:1250–1253
Cotty PJ (1989) Virulence and cultural characteristics of two Aspergillus flavus strains pathogenic on cotton. Phytopathology 79:808–814
Cotty PJ, Bhatnagar D (1994) Variability among atoxigenic Aspergillus flavus strains in ability to prevent aflatoxin contamination and production of aflatoxin biosynthetic pathway enzymes. Appl Environ Microbiol 60:2248–2251
Cotty PJ, Cardwell KF (1999) Divergence of West African and North American communities of Aspergillus section Flavi. Appl Environ Microbiol 65:2264–2266
Daniel PB, Walker WH, Habener JF (1998) Cyclic AMP signaling and gene regulation. Annu Rev Nutr 18:353–383
Demain AL, Fang A (2000) The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol 69:1–39
Dowd PF (1992) Insect interaction with mycotoxin-producing fungi and their hosts. In: Bhatnagar D, Lillehoj EB, Arora DK (eds) Handbook of applied mycology, vol V. Mycotoxins in ecological systems. Dekker, New York, pp 137–155
Drummond J, Pinnock DE (1990) Aflatoxin production by entomopathogenic isolates of Aspergillus parasiticus and Aspergillus flavus. J Invertebr Pathol 55:332–336
Dutton MF (1988) Enzymes and aflatoxin biosynthesis. Microbiol Rev 52:274–295
Eaton DL, Groopman JD (eds) (1994) The toxicology of aflatoxins: human health, veterinary, and agricultural significance. Academic Press, San Diego, Calif.
Ehrlich K, Cotty PJ (2002) Variability in nitrogen regulation of aflatoxin production by Aspergillus flavus strains. Appl Microbiol Biotechnol 60:174–178
Ehrlich KC, Montalbano BG, Bhatnagar D, Cleveland TE (1998) Alteration of different domains in AFLR affects aflatoxin pathway metabolism in Aspergillus parasiticus transformants. Fungal Genet Biol 23:279–287
Ehrlich KC, Cary JW, Montalbano BG (1999a) Characterization of the promoter for the gene encoding the aflatoxin biosynthetic pathway regulatory protein AFLR. Biochim Biophys Acta 1444:412–417
Ehrlich KC, Montalbano BG, Cary JW (1999b) Binding of the C6-zinc cluster protein, AFLR, to the promoters of aflatoxin pathway biosynthesis genes in Aspergillus parasiticus. Gene 230:249–257
Ehrlich KC, Montalbano BG, Cary JW, Cotty PJ (2002a) Promoter elements in the aflatoxin pathway polyketide synthase gene. Biochim Biophys Acta 1576:171–175
Ehrlich KC, Montalbano BG, Cotty PJ (2002b) Sequence comparison of aflR from different Aspergillus species provides evidence for variability in regulation of aflatoxin production. Fungal Genet Biol (in press) DOI s10.1016/S1087-1845(02)00509-1
Espeso EA, Arst HN Jr (2000) On the mechanism by which alkaline pH prevents expression of an acid-expressed gene. Mol Cell Biol 20:3355–3363
Feng GH, Leonard TJ (1995) Characterization of the polyketide synthase gene (pksL1) required for aflatoxin biosynthesis in Aspergillus parasiticus. J Bacteriol 177:6246–6254
Fernandes M, Keller NP, Adams TH (1998) Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol Microbiol 28:1355–1365
Flaherty JE, Payne GA (1997) Overexpression of aflR leads to upregulation of pathway gene expression and increased aflatoxin production in Aspergillus flavus. Appl Environ Microbiol 63:3995–4000
Frisvad JC (1985) Secondary metabolites as an aid to Emericella classification. In: Samson RA, Pitt JI (eds) Advances in Penicillium and Aspergillus systematics. Plenum Press, New York, pp 430–437
Geiser DM, Pitt JI, Taylor JW (1998) Cryptic speciation and recombination in the aflatoxin-producing fungus, Aspergillus flavus. Proc Natl Acad Sci USA 95:388–393
Geiser DM, Dorner JW, Horn BW, Taylor JW (2000) The phylogenetics of mycotoxin and sclerotium production in Aspergillus flavus and Aspergillus oryzae. Fungal Genet Biol 31:169–179
Hasan HA (1999) Phytotoxicity of pathogenic fungi and their mycotoxins to cereal seedling viability. Mycopathologia 148:149–155
Hicks JK, Yu JH, Keller NP, Adams TH (1997) Aspergillus sporulation and mycotoxin production both require inactivation of the FadA G alpha protein-dependent signaling pathway. EMBO J 16:4916–4923
Ito Y, Peterson SW, Wicklow DT, Goto T (2001) Aspergillus pseudotamarii, a new aflatoxin-producing species in Aspergillus section Flavi. Mycol Res 105:233–239
Jarvis BB, Miller JD (1996) Natural products, complexity and evolution. In: Romeo EA (ed) Phytochemical diversity and redundancy in ecological interactions. Plenum Press, New York, pp 265–295
Jarvis JL, Guthrie WD, Lillehoj EB (1984) Aflatoxin and selected biosynthetic precursors: effects on the European corn borer in the laboratory. J Agric Entomol 1:354–359
Jayashree T, Praveen Rao J, Subramanyam C (2000) Regulation of aflatoxin production by Ca2+/calmodulin-dependent protein phosphorylation and dephosphorylation. FEMS Microbiol Lett 183:215–219
Kachholz T, Demain AL (1983) Nitrate repression of averufin and aflatoxin biosynthesis. J Nat Prod 46:499–506
Kale SP, Cary JW, Bhatnagar D, Bennett JW (1996) Characterization of experimentally induced, nonaflatoxigenic variant strains of Aspergillus parasiticus. Appl Environ Microbiol 62:3399–3404
Keller NP, Watanabe CM, Kelkar HS, Adams TH, Townsend CA (2000) Requirement of monooxygenase-mediated steps for sterigmatocystin biosynthesis by Aspergillus nidulans. Appl Environ Microbiol 66:359–362
Khan SN, Venkitasubramanian TA (1986) 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 21:67–85
Khan SN, Venkitasubramanian TA (1987) Cyclic AMP pool and aflatoxin production in Aspergillus parasiticus NRRL 3240 and Aspergillus flavus NRRL 3537. Indian J Biochem Biophys 24:308–313
Klich MA, Mullaney EJ, Daly CB, Cary JW (2000) Molecular and physiological aspects of aflatoxin and sterigmatocystin biosynthesis by Aspergillus tamarii and A. ochraceoroseus. Appl Microbiol Biotechnol 53:605–609
Kulmberg P, Sequeval D, Lenouvel F, Mathieu M, Felenbok B (1992) Identification of the promoter region involved in the autoregulation of the transcriptional activator ALCR in Aspergillus nidulans. Mol Cell Biol 12:1932–1939
Kurtzman CP, Horn BW, Hesseltine CW (1987) Aspergillus nomius, a new aflatoxin-producing species related to Aspergillus flavus and Aspergillus tamarii. Antonie Van Leeuwenhoek 53:147–158
Kusumoto K, Hsieh DP (1996) Purification and characterization of the esterases involved in aflatoxin biosynthesis in Aspergillus parasiticus. Can J Microbiol 42:804–810
Lamb HK, Newton GH, Levett LJ, Cairns E, Roberts CF, Hawkins AR (1996) The QUTA activator and QUTR repressor proteins of Aspergillus nidulans interact to regulate transcription of quinate utilization pathway genes. Microbiology 142:1477–1490
Liang SH, Wu TS, Lee R, Chu FS, Linz JE (1997) Analysis of mechanisms regulating expression of the ver-1 gene, involved in aflatoxin biosynthesis. Appl Environ Microbiol 63:1058–1065
Lillehoj EB (1991) Aflatoxin: an ecologically elicited genetic activation signal. In: Smith JE, Henderson RS (eds) Mycotoxins and animal foods. CRC Press, Boca Raton, Fla., pp 2–30
Llewellyn GC, Gee CL, Sherertz PC (1988) Toxic responses of developing fifth instar milkweed bugs, Oncopeltus fasciatus (Hemiptera), to aflatoxin B1. Bull Environ Contam Toxicol 40:332–338
Marzluf GA (1997) Genetic regulation of nitrogen metabolism in the fungi. Microbiol Mol Biol Rev 61:17–32
Matsumura F, Knight SG (1967) Toxicity and chemosterilizing activity of aflatoxin against insects. J Econ Entomol 60:871–872
Matsushima K, Ando Y, Hamasaki T, Yabe K (1994) Purification and characterization of two versiconal hemiacetal acetate reductases involved in aflatoxin biosynthesis. Appl Environ Microbiol 60:2561–2567
Matsushima K, Chang PK, Yu J, Abe K, Bhatnagar D, Cleveland TE (2001) Pre-termination in AFLR of Aspergillus sojae inhibits aflatoxin biosynthesis. Appl Microbiol Biotechnol 55:585–589
Mayorga ME, Timberlake WE (1992) The developmentally regulated Aspergillus nidulans wA gene encodes a polypeptide homologous to polyketide and fatty acid synthases. Mol Gen Genet 235:205–212
McAlpin CE, Wicklow DT, Horn BW (2002) DNA fingerprinting analysis of vegetative compatibility groups in Aspergillus flavus from a peanut field in Georgia. Plant Dis 86:254–258
McLean M, Watt MP, Berjak P, Dutton MF (1995) Aflatoxin B1—its effects on an in vitro plant system. Food Addit Contam 12:435–443
Meyers DM, O'Brian G, Du WL, Bhatnagar D, Payne GA (1998) Characterization of aflJ, a gene required for conversion of pathway intermediates to aflatoxin. Appl Environ Microbiol 64:3713–3717
Minto RE, Townsend CA (1997) Enzymology and molecular biology of aflatoxin biosynthesis. Chem Rev 97:2537–2555
Muro-Pasteur MI, Gonzalez R, Strauss J, Narendja F, Scazzocchio C (1999) The GATA factor AreA is essential for chromatin remodelling in a eukaryotic bidirectional promoter. EMBO J 18:1584–1597
Ozcan S, Leong T, Johnston M (1996) Rgt1p of Saccharomyces cerevisiae, a key regulator of glucose-induced genes, is both an activator and a repressor of transcription. Mol Cell Biol 16:6419–6426
Parthun MR, Jaehning JA (1992) A transcriptionally active form of GAL4 is phosphorylated and associated with GAL80. Mol Cell Biol 12:4981–4987
Payne GA, Brown MP (1998) Genetics and physiology of aflatoxin biosynthesis. Annu Rev Phytopathol 36:329–362
Payne GA, Nystorm GJ, Bhatnagar D, Cleveland TE, Woloshuk CP (1993) Cloning of the afl-2 gene involved in aflatoxin biosynthesis from Aspergillus flavus. Appl Environ Microbiol 59:156–162
Peterson SW, Ito Y, Horn BW, Goto T (2001) Aspergillus bombycis, a new aflatoxigenic species and genetic variation in its sibling species, A. nomius. Mycologia 93:689–703
Prieto R, Woloshuk CP (1997) ord1, an oxidoreductase gene responsible for conversion of O-methylsterigmatocystin to aflatoxin in Aspergillus flavus. Appl Environ Microbiol 63:1661–1666
Rechsteiner M (1988) Regulation of enzyme levels by proteolysis: the role of PEST regions. Adv Enzyme Regul 27:135–151
Reece RJ, Ptashne M (1993) Determinants of binding-site specificity among yeast C6 zinc cluster proteins. Science 261:909–911
Reiss J (1975) Insecticidal and larvicidal activities of the mycotoxins aflatoxin B1, rubratoxin B, patulin and diacetoxyscirpenol towards Drosophila melanogaster. Chem Biol Interact 10:339–342
Silva JC, Minto RE, Barry CE 3rd, Holland KA, Townsend CA (1996) Isolation and characterization of the versicolorin B synthase gene from Aspergillus parasiticus. Expansion of the aflatoxin B1 biosynthetic gene cluster. J Biol Chem 271:13600–13608
Skory CD, Chang PK, Cary J, Linz JE (1992) Isolation and characterization of a gene from Aspergillus parasiticus associated with the conversion of versicolorin A to sterigmatocystin in aflatoxin biosynthesis. Appl Environ Microbiol 58:3527–3537
Suarez T, Oestreicher N, Penalva MA, Scazzocchio C (1991) Molecular cloning of the uaY regulatory gene of Aspergillus nidulans reveals a favoured region for DNA insertions. Mol Gen Genet 230:369–375
Tag A, Hicks J, Garifullina G, Ake C, Phillips TD, Beremand M, Keller N (2000) G-protein signalling mediates differential production of toxic secondary metabolites. Mol Microbiol 38:658–665
Takahashi T, Chang P-K, Matsushima K, Yu J, Abe K, Bhatnagar D, Cleveland TE, Koyama Y (2002) Non-functionality of Aspergillus sojae aflR in a strain of Aspergillus parasiticus with a disrupted aflR gene. Appl Environ Microbiol 68:3737–3743
Tilburn J, Sarkar S, Widdick DA, Espeso EA, Orejas M, Mungroo J, Penalva MA, Arst HN Jr (1995) The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J 14:779–790
Todd RB, Andrianopoulos A, Davis MA, Hynes MJ (1998) FacB, the Aspergillus nidulans activator of acetate utilization genes, binds dissimilar DNA sequences. EMBO J 17:2042–2054
Trail F, Chang P-K, Cary J, Linz JE (1994) Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins by Aspergillus parasiticus. Appl Environ Microbiol 60:4078–4085
Trail F, Mahanti N, Linz J (1995a) Molecular biology of aflatoxin biosynthesis. Microbiology 141:755–765
Trail F, Mahanti N, Rarick M, Mehigh R, Liang SH, Zhou R, Linz JE (1995b) 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 61:2665–2673
Walton JD (2000) Horizontal gene transfer and evolution of secondary metabolite clusters in fungi: an hypothesis. Fungal Genet Biol 30:167–171
Wang Z, Tong Z, Cong L (1996) Relationship between aflatoxin and sclerotia production in Aspergillus flavus. Chung Hua Yu Fang I Hsueh Tsa Chih 30:14–16
Watanabe CM, Wilson D, Linz JE, Townsend CA (1996) Demonstration of the catalytic roles and evidence for the physical association of type I fatty acid synthases and a polyketide synthase in the biosynthesis of aflatoxin B1. Chem Biol 3:463–469
Watson AJ, Fuller LJ, Jeenes DJ, Archer DB (1999) Homologs of aflatoxin biosynthesis genes and sequence of aflR in Aspergillus oryzae and Aspergillus sojae. Appl Environ Microbiol 65:307–310
Woloshuk CP, Prieto R (1998) Genetic organization and function of the aflatoxin B1 biosynthetic genes. FEMS Microbiol Lett 160:169–176
Woloshuk CP, Foutz KR, Brewer JF, Bhatnagar D, Cleveland TE, Payne GA (1994) Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis. Appl Environ Microbiol 60:2408–2414
Wright VF, Vesonder RF, Ciegler A (1982) Mycotoxins and other fungal metabolites as insecticides. In: Kurstak E (ed) Microbial and viral pesticides. Dekker, New York, pp 559–583
Xiao X, Fu YH, Marzluf GA (1995) The negative acting NMR regulatory protein of Neurospora crassa binds to and inhibits the DNA-binding activity of the positive-acting nitrogen regulating protein, NIT2. Biochemistry 34:8861–8868
Xie Y, Denison C, Yang SH, Fancy DA, Kodadek T (2000) Biochemical characterization of the TATA-binding protein-Gal4 activation domain complex. J Biol Chem 275:31914–31920
Yabe K, Ando Y, Hamasaki T (1991) A metabolic grid among versiconal hemiacetal acetate, versiconol acetate, versiconol and versiconal during aflatoxin biosynthesis. J Gen Microbiol 137:2469–2475
Yabe K, Nakamura M, Hamasaki T (1999) Enzymatic formation of G-group aflatoxins and biosynthetic relationship between G- and B-group aflatoxins. Appl Environ Microbiol 65:3867–3872
Yu J, Chang P-K, Cary JW, Wright M, Bhatnagar D, Cleveland TE, Payne GA, Linz JE (1995) Comparative mapping of aflatoxin pathway gene clusters in Aspergillus parasiticus and Aspergillus flavus. Appl Environ Microbiol 61:2365–2371
Yu JH, Butcho RA, Fernandes M, Keller NP, Leonard TJ, Adams TH (1996) Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus. Curr Genet 29:549–555
Yu J, Chang P-K, Cary JW, Bhatnagar D, Cleveland TE (1997) 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 63:1349–1356
Yu J, Chang P-K, Ehrlich KC, Cary JW, Montalbano B, Dyer JM, Bhatnagar D, Cleveland TE (1998) Characterization of the critical amino acids of an Aspergillus parasiticus cytochrome P-450 monooxygenase encoded by ordA that is involved in the biosynthesis of aflatoxins B1, G1, B2, and G2. Appl Environ Microbiol 64:4834–4841
Yu J, Chang P-K, Bhatnagar D, Cleveland TE (2000a) Genes encoding cytochrome P450 and monooxygenase enzymes define one end of the aflatoxin pathway gene cluster in Aspergillus parasiticus. Appl Microbiol Biotechnol 53:583–590
Yu J, Chang P-K, Bhatnagar D, Cleveland TE (2000b) Cloning of a sugar utilization gene cluster in Aspergillus parasiticus. Biochim Biophys Acta 1493:211–214
Zhou R, Linz JE (1999) Enzymatic function of the nor-1 protein in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 65:5639–5641
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Bhatnagar, D., Ehrlich, K.C. & Cleveland, T.E. Molecular genetic analysis and regulation of aflatoxin biosynthesis. Appl Microbiol Biotechnol 61, 83–93 (2003). https://doi.org/10.1007/s00253-002-1199-x
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DOI: https://doi.org/10.1007/s00253-002-1199-x