Advances in research of the structural gene characteristics of the aflatoxin biosynthetic gene cluster

Main Article Content

Qi-Zhang Li
Zhu-Mei He*

Abstract

Aflatoxins, produced by Aspergillus spp., are strongly toxic and carcinogenic fungal secondary metabolites. Aflatoxin biosynthesis is a complex process and involves at least 30 genes clustered within an approximately 75 kB gene cluster. In this paper, we reviewed current status of the researches on the characterized structural genes involved in aflatoxin biosynthesis and their roles in aflatoxin-producing fungi, especially in A. flavus and A. parasiticus, which will improve our understanding of the mechanism of aflatoxin biosynthesis and regulation and provide reference for further study.

Article Details

Li, Q.-Z., & He, Z.-M. (2018). Advances in research of the structural gene characteristics of the aflatoxin biosynthetic gene cluster. Journal of Plant Science and Phytopathology, 2(3), 068–082. https://doi.org/10.29328/journal.jpsp.1001022
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Eaton DL, Gallagher EP. Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 1994; 34: 135-172. Ref.: https://goo.gl/8JAKV7

>Bennett JW. Mycotoxins, mycotoxicoses, mycotoxicology and Mycopathologia. Mycopathologia. 1987; 100: 3-5. Ref.: https://goo.gl/CmPAS5

Massey TE, Stewart RK, Daniels JM, Liu L. Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B1 carcinogenicity. Proc Soc Exp Biol Med. 1995; 208: 213-227. Ref.: https://goo.gl/d9y8sT

Yu J, Chang PK, Cary JW, Wright M, Bhatnagar D, et al. Comparative mapping of aflatoxin pathway gene clusters in Aspergillus parasiticus and Aspergillus flavus. Appl Environ Microbiol. 1995; 61: 2365-2371. Ref.: https://goo.gl/QAQBW8

Yu J. Current understanding on aflatoxin biosynthesis and future perspective in reducing aflatoxin contamination. Toxins (Basel). 2012; 4: 1024-1057. Ref.: https://goo.gl/CZ694W

Ehrlich KC, Yu J, Cotty PJ. Aflatoxin biosynthesis gene clusters and flanking regions. J Appl Microbiol. 2005; 99: 518-527. Ref.: https://goo.gl/LQLFdo

Yu J, Chang PK, Ehrlich KC, Cary JW, Bhatnagar D, et al. Clustered pathway genes in aflatoxin biosynthesis. Appl Environ Microbiol. 2004; 70: 1253-1262. Ref.: https://goo.gl/zbda36

Yabe K, Nakajima H. Enzyme reactions and genes in aflatoxin biosynthesis. Appl Microbiol Biotechnol. 2004; 64: 745-755. Ref.: https://goo.gl/zPC4Sf

Bhatnagar D, Ehrlich KC, Cleveland TE. Molecular genetic analysis and regulation of aflatoxin biosynthesis. Appl Microbiol Biotechnol. 2003; 61: 83-93. https://goo.gl/L5eeWW

Yabe K, Ando Y, Hamasaki T. Biosynthetic relationship among aflatoxins B1, B2, G1, and G2. Appl Environ Microbiol. 1988; 54: 2101-2106. Ref.: https://goo.gl/PLn7Uw

Trucksess MW, Mislivec PB, Young K, Bruce VR, Page SW. Cyclopiazonic acid production by cultures of Aspergillus and Penicillium species isolated from dried beans, corn meal, macaroni, and pecans. J Assoc Off Anal Chem. 1987; 70: 123-126. Ref.: https://goo.gl/LbmR4V

Rosfarizan M, Ariff AB, Hassan MA, Karim MI. Kojic acid production by Aspergillus flavus using gelatinized and hydrolyzed sago starch as carbon sources. Folia Microbiol (Praha). 1998; 43: 459-464. Ref.: https://goo.gl/TfxyP6

Ehrlich KC. Predicted roles of the uncharacterized clustered genes in aflatoxin biosynthesis. Toxins (Basel). 2009; 1: 37-58. Ref.: https://goo.gl/rsMKXe

Watanabe CM, Wilson D, Linz JE, Townsend CA. 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. 1996; 3: 463-469. Ref.: https://goo.gl/bjsyQ1

Watanabe CM, Townsend CA. Initial characterization of a type I fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin B(1). Chem Biol. 2002; 9: 981-988. Ref.: https://goo.gl/q7jwaT

Hitchman TS, Schmidt EW, Trail F, Rarick MD, Linz JE, et al. Hexanoate synthase, a specialized type I fatty acid synthase in aflatoxin B1 biosynthesis. Bioorg Chem. 2001; 29: 293-307. Ref.: https://goo.gl/YfrbLn

Townsend CA, Christensen SB, Trautwein K. Hexanoate as a starter unit in polyketide biosynthesis. J Am Chem Soc. 1984; 106: 3868-3869. Ref.: https://goo.gl/Ua2fQB

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. Ref.: https://goo.gl/DeXEb9

Hong SY, Roze LV, Wee J, Linz JE. Evidence that a transcription factor regulatory network coordinates oxidative stress response and secondary metabolism in aspergilli. Microbiologyopen. 2013; 2: 144-160. Ref.: https://goo.gl/AkvVWj

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: 27428-27439. Ref.: https://goo.gl/BUJME6

Roze LV, Chanda A, 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: 35137-35148. Ref.: https://goo.gl/fXmhTw

Crawford JM, Dancy BC, Hill EA, Udwary DW, Townsend CA. Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. Proc Natl Acad Sci U S A. 2006; 103: 16728-16733. Ref.: https://goo.gl/R1JscB

Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, et al. Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature. 2009; 461: 1139-1143. Ref.: https://goo.gl/95sTJk

Chang PK, Cary JW, Yu J, Bhatnagar D, Cleveland TE. The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis. Mol Gen Genet. 1995; 248: 270-277. Ref.: https://goo.gl/b2iYwm

Trail F, Mahanti N, Rarick M, Mehigh R, Liang SH, 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. Ref.: https://goo.gl/nkPc5w

Feng GH, Leonard TJ. Characterization of the polyketide synthase gene (pksL1) required for aflatoxin biosynthesis in Aspergillus parasiticus. J Bacteriol. 1995; 177: 6246-6254. Ref.: https://goo.gl/M4Kgf7

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. Ref.: https://goo.gl/93LpKG

Ehrlich KC, Montalbano BG, Cary JW, Cotty PJ. Promoter elements in the aflatoxin pathway polyketide synthase gene. Biochim Biophys Acta. 2002; 1576: 171-175. Ref.: https://goo.gl/GW2XiA

Udwary DW, Merski M, Townsend CA. A method for prediction of the locations of linker regions within large multifunctional proteins, and application to a type I polyketide synthase. J Mol Biol. 2002; 323: 585-598. Ref.: https://goo.gl/P7gSqS

Crawford JM, Vagstad AL, Ehrlich KC, Townsend CA. Starter unit specificity directs genome mining of polyketide synthase pathways in fungi. Bioorg Chem. 2008; 36: 16-22. Ref.: https://goo.gl/e7uUnF

Crawford JM, Thomas PM, Scheerer JR, Vagstad AL, Kelleher NL, et al. Deconstruction of iterative multidomain polyketide synthase function. Science. 2008; 320: 243-246. Ref.: https://goo.gl/XARYms

Bennett JW, Christensen SB. New perspectives on aflatoxin biosynthesis. Adv Appl Microbiol. 1983; 29: 53-92. Ref.: https://goo.gl/LdqTXq

Ehrlich KC, Scharfenstein LL Jr., Montalbano BG, Chang PK. Are the genes nadA and norB involved in formation of aflatoxin G(1)? Int J Mol Sci. 2008; 9: 1717-1729. Ref.: https://goo.gl/V8fJv4

Zhou R, Linz JE. Enzymatic function of the nor-1 protein in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol. 1999; 65: 5639-5641. Ref.: https://goo.gl/8VYKGB

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. Ref.: https://goo.gl/bvqnoQ

Miller MJ, Roze LV, Trail F, Linz JE. Role of cis-acting sites NorL, a TATA box, and AflR1 in nor-1 transcriptional activation in Aspergillus parasiticus. Appl Environ Microbiol. 2005; 71: 1539-1545. Ref.: https://goo.gl/YwkVTu

Yabe K, Nakamura Y, Nakajima H, Ando Y, Hamasaki T. Enzymatic conversion of norsolorinic acid to averufin in aflatoxin biosynthesis. Appl Environ Microbiol. 1991; 57: 1340-1345. Ref.: https://goo.gl/T1SZo4

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. Ref.: https://goo.gl/VA1iw1

Yu J, Bhatnagar D, Cleveland TE. Completed sequence of aflatoxin pathway gene cluster in Aspergillus parasiticus. FEBS Lett. 2004; 564: 126-130. Ref.: https://goo.gl/MEzEze

Ehrlich KC, Chang PK, Yu J, Cotty PJ. Aflatoxin biosynthesis cluster gene cypA is required for G aflatoxin formation. Appl Environ Microbiol. 2004; 70: 6518-6524. Ref.: https://goo.gl/Ukixmd

Chang PK, Yu J, Ehrlich KC, Boue SM, Montalbano BG, et al. adhA in Aspergillus parasiticus is involved in conversion of 5'-hydroxyaverantin to averufin. Appl Environ Microbiol. 2000; 66: 4715-4719. Ref.: https://goo.gl/q8HbAL

Bateman A, Birney E, Durbin R, Eddy SR, Finn RD, et al. Pfam 3.1: 1313 multiple alignments and profile HMMs match the majority of proteins. Nucleic Acids Res. 1999; 27: 260-262. Ref.: https://goo.gl/DvrSZ5

Sakuno E, Yabe K, Nakajima H. Involvement of two cytosolic enzymes and a novel intermediate, 5'-Oxoaverantin, in the pathway from 5'-Hydroxyaverantin to averufin in aflatoxin biosynthesis. Appl Environ Microbiol. 2003; 69: 6418-6426. Ref.: https://goo.gl/uJYiWt

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. Ref.: https://goo.gl/1LwU74

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. Ref.: https://goo.gl/oSedyJ

Yabe K, Chihaya N, Hamamatsu S, Sakuno E, Hamasaki T, et al. Enzymatic conversion of averufin to hydroxyversicolorone and elucidation of a novel metabolic grid involved in aflatoxin biosynthesis. Appl Environ Microbiol. 2003; 69: 66-73. Ref.: https://goo.gl/Zry8nN

Yu J, Chang PK, Bhatnagar D, Cleveland TE. Genes encoding cytochrome P450 and monooxygenase enzymes define one end of the aflatoxin pathway gene cluster in Aspergillus parasiticus. Appl Microbiol Biotechnol. 2000; 53: 583-590. Ref.: https://goo.gl/cyqcvZ

Cary JW, Ehrlich KC, Bland JM, Montalbano BG. The aflatoxin biosynthesis cluster gene, aflX, encodes an oxidoreductase involved in conversion of versicolorin A to demethylsterigmatocystin. Appl Environ Microbiol. 2006; 72: 1096-1101. Ref.: https://goo.gl/CG9Sxb

Ehrlich KC, Montalbano B, Boue SM, Bhatnagar D. An aflatoxin biosynthesis cluster gene encodes a novel oxidase required for conversion of versicolorin a to sterigmatocystin. Appl Environ Microbiol. 2005; 71: 8963-8965. Ref.: https://goo.gl/iPggiS

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. Ref.: https://goo.gl/uUepJY

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. Ref.: https://goo.gl/YVtkf2

Hallam SE, Malpartida F, Hopwood DA. Nucleotide sequence, transcription and deduced function of a gene involved in polyketide antibiotic synthesis in Streptomyces coelicolor. Gene. 1988; 74: 305-320. Ref.: https://goo.gl/EPXthu

Delledonne M, Porcari R, Fogher C. Nucleotide sequence of the nodG gene of Azospirillum brasilense. Nucleic Acids Res. 1990; 18: 6435. Ref.: https://goo.gl/6G4AsR

Heilmann HJ, Magert HJ, Gassen HG. Identification and isolation of glucose dehydrogenase genes of Bacillus megaterium M1286 and their expression in Escherichia coli. Eur J Biochem. 1988; 174: 485-490. Ref.: https://goo.gl/rUd2k4

Hopwood DA, Sherman DH. Molecular genetics of polyketides and its comparison to fatty acid biosynthesis. Annu Rev Genet. 1990; 24: 37-66. Ref.: https://goo.gl/1AwzYP

Kamps MP, Taylor SS, Sefton BM. Direct evidence that oncogenic tyrosine kinases and cyclic AMP-dependent protein kinase have homologous ATP-binding sites. Nature. 1984; 310: 589-592. Ref.: https://goo.gl/R3KUKy

Udwary DW, Casillas LK, Townsend CA. Synthesis of 11-hydroxyl O-methylsterigmatocystin and the role of a cytochrome P-450 in the final step of aflatoxin biosynthesis. J Am Chem Soc. 2002; 124: 5294-5303. Ref.: https://goo.gl/2ju9Au

Price MS, Yu J, Nierman WC, Kim HS, Pritchard B, et al. The aflatoxin pathway regulator AflR induces gene transcription inside and outside of the aflatoxin biosynthetic cluster. FEMS Microbiol Lett. 2006; 255: 275-279. Ref.: https://goo.gl/kmx4hm

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. Ref.: https://goo.gl/4emi7c

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. Ref.: https://goo.gl/oapVdn

Keller NP, Watanabe CM, Kelkar HS, Adams TH, Townsend CA. Requirement of monooxygenase-mediated steps for sterigmatocystin biosynthesis by Aspergillus nidulans. Appl Environ Microbiol. 2000; 66: 359-362. Ref.: https://goo.gl/iwAA8S

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. Ref.: https://goo.gl/dr19gi

Bhatnagar D, Cleveland TE, Kingston DG. Enzymological evidence for separate pathways for aflatoxin B1 and B2 biosynthesis. Biochemistry. 1991; 30: 4343-4350. Ref.: https://goo.gl/KMPVYv

Yabe K, Ando Y, Hamasaki T. Desaturase activity in the branching step between aflatoxins B1 and G1 and aflatoxins B2 and G2. Agric Biol Chem. 1991; 55: 1907-1911. Ref.: https://goo.gl/t6DqxM

Kelkar HS, 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. Ref.: https://goo.gl/RTJcZ6

Keller NP, Segner S, Bhatnagar D, Adams TH. stcS, a putative P-450 monooxygenase, is required for the conversion of versicolorin A to sterigmatocystin in Aspergillus nidulans. Appl Environ Microbiol. 1995; 61: 3628-3632. Ref.: https://goo.gl/c76Qba

Calvo AM, Wilson RA, Bok JW, Keller NP. Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev. 2002; 66: 447-459. Ref.: https://goo.gl/BAePgG

Reiss J. Development of Aspergillus parasiticus and formation of aflatoxin B1 under the influence of conidiogenesis affecting compounds. Arch Microbiol. 1982; 133: 236-238. Ref.: https://goo.gl/KQR3cu

Wieser J, Yu JH, Adams TH. Dominant mutations affecting both sporulation and sterigmatocystin biosynthesis in Aspergillus nidulans. Curr Genet. 1997; 32: 218-224. Ref.: https://goo.gl/bQdk9g

Prieto R, Yousibova GL, Woloshuk CP. Identification of aflatoxin biosynthesis genes by genetic complementation in an Aspergillus flavus mutant lacking the aflatoxin gene cluster. Appl Environ Microbiol. 1996; 62: 3567-3571. Ref.: https://goo.gl/SbGCgC

Yu J, Chang PK, Ehrlich KC, Cary JW, Montalbano B, et al. 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. 1998; 64: 4834-4841. Ref.: https://goo.gl/CAFAPM

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. Ref.: https://goo.gl/7Huf4a

Cai J, Zeng H, Shima Y, Hatabayashi H, Nakagawa H, et al. Involvement of the nadA gene in formation of G-group aflatoxins in Aspergillus parasiticus. Fungal Genet Biol. 2008; 45: 1081-1093. Ref.: https://goo.gl/y6VNYo

Yu J, Chang P, Bhatnagar D, Cleveland TE. Cloning of a sugar utilization gene cluster in Aspergillus parasiticus. Biochim Biophys Acta. 2000; 1493: 211-214. Ref.: https://goo.gl/u8AkSx

Fox KM, Karplus PA. Old yellow enzyme at 2 Å resolution: overall structure, ligand binding, and comparison with related flavoproteins. Structure. 1994; 2: 1089-1105. Ref.: https://goo.gl/oEWSf6

Williams RE, Bruce NC. 'New uses for an Old Enzyme'--the Old Yellow Enzyme family of flavoenzymes. Microbiology. 2002; 148: 1607-1614. Ref.: https://goo.gl/QRPEoA

Sakuno E, Wen Y, Hatabayashi H, Arai H, Aoki C, et al. Aspergillus parasiticus cyclase catalyzes two dehydration steps in aflatoxin biosynthesis. Appl Environ Microbiol. 2005; 71: 2999-3006. Ref.: https://goo.gl/doux9q

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. Biochemistry. 1996; 35: 11470-11486. Ref.: https://goo.gl/A3KPSS

Lin BK, Anderson JA. Purification and properties of versiconal cyclase from Aspergillus parasiticus. Arch Biochem Biophys. 1992; 293: 67-70. Ref.: https://goo.gl/XHcZKv

Silva JC, Minto RE, Barry CE 3rd, Holland KA, Townsend CA. Isolation and characterization of the versicolorin B synthase gene from Aspergillus parasiticus. Expansion of the aflatoxin b1 biosynthetic gene cluster. J Biol Chem. 1996; 271: 13600-13608. Ref.: https://goo.gl/rjgw9B

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: 804-813. Ref.: https://goo.gl/Vgk1c4

Juvvadi PR, Chivukula S. Putative calmodulin-binding domains in aflatoxin biosynthesis-regulatory proteins. Curr Microbiol. 2006; 52: 493-496. Ref.: https://goo.gl/Zn1k4d

Hsieh DP, Wan CC, Billington JA. A versiconal hemiacetal acetate converting enzyme in aflatoxin biosynthesis. Mycopathologia. 1989; 107: 121-126. Ref.: https://goo.gl/vBLdB5

Kusumoto K, Hsieh DP. Purification and characterization of the esterases involved in aflatoxin biosynthesis in Aspergillus parasiticus. Can J Microbiol. 1996; 42: 804-810. Ref.: https://goo.gl/bUqseb

Yu J, Chang PK, Bhatnagar D, Cleveland TE. Cloning and functional expression of an esterase gene in Aspergillus parasitcus. Mycopathologia. 2002; 156: 227-234. Ref.: https://goo.gl/8uP3Dv

Yabe K, Ando Y, Hashimoto J, Hamasaki T. Two distinct O-methyltransferases in aflatoxin biosynthesis. Appl Environ Microbiol. 1989; 55: 2172-2177. Ref.: https://goo.gl/DVHfJM

Yabe K, Matsushima K, Koyama T, Hamasaki T. Purification and characterization of O-methyltransferase I involved in conversion of demethylsterigmatocystin to sterigmatocystin and of dihydrodemethylsterigmatocystin to dihydrosterigmatocystin during aflatoxin biosynthesis. Appl Environ Microbiol. 1998; 64: 166-171. Ref.: https://goo.gl/fTbHrK

Yu J, Chang PK, Payne GA, Cary JW, Bhatnagar D, et al. Comparison of the omtA genes encoding O-methyltransferases involved in aflatoxin biosynthesis from Aspergillus parasiticus and A. flavus. Gene. 1995; 163: 121-125. Ref.: https://goo.gl/DKUJvr

Yu J, Cary JW, Bhatnagar D, Cleveland TE, Keller NP, et al. Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O-methyltransferase involved in aflatoxin biosynthesis. Appl Environ Microbiol. 1993; 59: 3564-3571. Ref.: https://goo.gl/NMdDbf

Chauvaux S, Chevalier F, Le Dantec C, Fayolle F, Miras I, et al. Cloning of a genetically unstable cytochrome P-450 gene cluster involved in degradation of the pollutant ethyl tert-butyl ether by Rhodococcus ruber. J Bacteriol. 2001; 183: 6551-6557. Ref.: https://goo.gl/pE99zQ

Lin JQ, Zhao XX, Zhi QQ, Zhao M, He ZM. Transcriptomic profiling of Aspergillus flavus in response to 5-azacytidine. Fungal Genet Biol. 2013; 56:78-86. Ref.: https://goo.gl/HtSYFA

Liu SY, Lin JQ, Wu HL, Wang CC, Huang SJ, et al. Bisulfite sequencing reveals that Aspergillus flavus holds a hollow in DNA methylation. PLoS ONE. 2012; 7: e30349. Ref.: https://goo.gl/7htLt5

Zhi QQ, Li JY, Liu QY, He ZM. A cytosine methyltransferase ortholog dmtA is involved in the sensitivity of Aspergillus flavus to environmental stresses. Fungal Biol. 2017; 121: 501-514. Ref.: https://goo.gl/wv4WPa

Zhi QQ, Xie YY, He ZM. Genome mining for aflatoxin biosynthesis. Fungal Genom Biol. 2013; 3: 108. Ref.: https://goo.gl/cGGv39

Zhao X, Spraker JE, Bok JW, Velk T, He ZM, Keller NP. A cellular fusion cascade regulated by LaeA is required for sclerotial development in Aspergillus flavus. Front Microbiol. 2017; 8: 1925. Ref.: https://goo.gl/N6zB77

Zhao X, Zhi QQ, Li JY, Keller NP, He ZM. The antioxidant gallic acid inhibits aflatoxin formation in Aspergillus flavus by modulating transcription factors FarB and CreA. Toxins (Basel). 2018; 10: 270. Ref.: https://goo.gl/PczwsJ

Chang PK, Skory CD, Linz JE. Cloning of a gene associated with aflatoxin B1 biosynthesis in Aspergillus parasiticus. Curr Genet. 1992; 21: 231-233. Ref.: https://goo.gl/oTTyhx

Lin JQ, Zhao XX, Wang CC, Xie Y, Li GH, et al. Transcriptomic profiling of Aspergillus flavus in response to 5-azacytidine. Ann Microbiol. 2012; 63: 763-769. Ref.: https://goo.gl/46h5qV

Nierman WC, Yu J, Fedorova-Abrams ND, Losada L, Cleveland TE, et al. Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes aflatoxin contamination of food and feed. Genome Announc. 2015; 3. Ref.: https://goo.gl/7ijZGU