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Enzyme reactions and genes in aflatoxin biosynthesis

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Abstract

Aflatoxins are highly toxic and carcinogenic substances mainly produced by Aspergillus flavus and Aspergillus parasiticus. Sterigmatocystin is a penultimate precursor of aflatoxins and also a toxic and carcinogenic substance produced by many species, including Aspergillus nidulans. Recently, the majority of the enzyme reactions involved in aflatoxin/sterigmatocystin biosynthesis have been clarified, and the genes encoding the enzymes have been isolated. Most of the genes constitute a large gene cluster in the fungal genome, and their expression is mostly regulated by a product of the regulatory gene aflR. This review will summarize the enzymatic steps and the genes in aflatoxin/sterigmatocystin biosynthesis.

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References

  • Bennett JW, Christensen SB (1983) New perspective of aflatoxin biosynthesis. Adv Appl Microbiol 29:53–92

    CAS  PubMed  Google Scholar 

  • Bennett JW, Deutsch E (1986) Genetics of mycotoxin biosynthesis. In: Steyn PS,Eleggaar R (eds) Mycotoxins and phycotoxins. Elsevier, Amsterdam, pp 51–64

  • Bennett JW, Lee LS, Cucullu AF (1976) Effect of dichlorvos on aflatoxin and versicolorin A production in Aspergillus parasiticus. Bot Gaz 137:318–324

    Article  CAS  Google Scholar 

  • Bergar-Deguee M, Bergar Y (1982) Structure of versicolorone isolated from Aspergillus versicolor. Phytochemistry 21:1449–1451

    Article  Google Scholar 

  • Bhatnagar D, Cleveland TE (1990) Purification and characterization of a reductase from Aspergillus parsiticus SRRC 2043 involved in aflatoxin biosynthesis. FASEB J 4:A2164

    Google Scholar 

  • Bhatnagar D, McCormick SP, Lee LS, Hill RA (1987) Identification of O-methylsterigmatocystin as an aflatoxin B1/G1 precursor in Aspergillus parasicitus. Appl Environ Microbiol 53:1028–1033

    CAS  PubMed  Google Scholar 

  • Bhatnagar D, Ehrlich KC, Cleveland TE (2003) Molecular genetic analysis and regulation of aflatoxin biosynthesis. Appl Microbiol Biotechnol 61:83–93

    CAS  PubMed  Google Scholar 

  • Brown DW, Adams TH, Keller NP (1996a) Aspergillus has distinct fatty acid synthases for primary and secondary metabolism. Proc Natl Acad Sci USA 93:14873–14877

    Article  CAS  PubMed  Google Scholar 

  • Brown DW, Yu JH, Kelkar HS, Fernandes M, Nesbitt TC, Keller NP, Adams TH, Leonard TJ (1996b) Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. Proc Natl Acad Sci USA 93:1418–1422

    Article  CAS  PubMed  Google Scholar 

  • Brown MP, Brouwn-Jenco CS, Payne GA (1999) Genetic and molecular analysis of aflatoxin biosynthesis. Fungal Genet Biol 26:81–98

    Article  CAS  PubMed  Google Scholar 

  • Busby WF, Wogan GN (1985) Aflatoxins. P. 945–1136. In: Esarle CE (ed) Chemical carcinogens, 2nd edn, vol 2. American Chemical Society, Washington, D.C

  • Cary JW, Wright M, Bhatnagar D, Lee R, Chu FS (1996) Molecular characterization of an Aspergillus parasiticus dehydrogenase gene, norA, located on the aflatoxin biosynthesis gene cluster. Appl Environ Microbiol 62:360–366

    Google Scholar 

  • Cary JW, Barnaby N, Ehrlich KC, Bhatnagar D (1999) Isolation and characterization of experimentally induced aflatoxins biosynthetic pathway deletion mutants of Aspergillus parasiticus. Appl Microbiol Biotechnol 51:808–812

    Article  CAS  PubMed  Google Scholar 

  • Cary JW, Bhatnagar D, Linz JE (2000) Aflatoxins: Biological significance and regulation of biosynthesis. In: Cary JW, Linz JE, Bhatnager D (eds), Microbial food-borne diseases: mechanisms of pathogenesis and toxin synthesis. Technomic, Lancester, Pennsylvania, pp 317–361

  • Chang PK, Cary JW, Yu J, Bhatnagar D, Cleveland TE (1995) Aspergillus parasiticus polyketide synthetase gene, pksA, a homolog of Aspergillus nidulans wA, required for aflatoxin B1. Mol Gen Genet 248:270–277

    CAS  PubMed  Google Scholar 

  • Chang PK, Yu J, Bhatnagar D, Cleveland TE (1999) 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

    CAS  PubMed  Google Scholar 

  • Chang PK, Yu J, Ehrlich KC, Boue SM, Montalbano BG, Bhatnagar D, Cleveland TE (2000) The aflatoxin biosynthesis gene adhA in Aspergillus parasiticus is involved in conversion of 5’-hydroxyaverantin to averufin. Appl Environ Microbiol 66:4715–4719

    Google Scholar 

  • Feng GH, Leonard TJ (1995) Characterization of the polyketide synthase gene (pksL) required for aflatoxin biosynthesis in Aspergillus parasiticus. J Bacteriol 177:6246–5624

    CAS  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Hamasaki T, Matsui K, Isono K, Hatsuda Y (1973) A new metabolite from Aspergillus versicolor. Agric Biol Chem 37:1769–1770

    CAS  Google Scholar 

  • Hitchman TS, Schmidt EW, Trail F, Rarick MD, Linz JE, Townsend CA (2001) Bioorg Chem 29:293–307

    Article  CAS  Google Scholar 

  • Horie Y, Udagawa S, Nishimura K, Miyaji M (1988) Distribution of sterigmatocystin-producing Emericella in soil. In: Aibara K, Kumagai S, Ostubo K, Yoshizawa T (eds) Proceeding Jap Assoc/Mycotoxicology, Suppl. I, IUPAC, Mycotoxins and Phycotoxins. Jpn Soc Mycotoxicology, Tokyo, pp 41–42

  • Hutchinson CR (1999) Microbial polyketide synthases: more and more prolific. Proc Natl Acad Sci USA 96:3336–3338

    CAS  PubMed  Google Scholar 

  • Kelkar HS, Keller NP, Adams TH (1996) Aspergillus nidulans stcP encodes an O-methyltransferase that is required for sterigmatocystin biosynthesis. Appl Environ Microbiol 62:4296–4298

    CAS  PubMed  Google Scholar 

  • Kelkar HS, Hernant S, Skloss TW, Haw JF, Keller NP, Adams TH (1997) Aspergillus nidulans stcL encodes a putative cytochrome P-450 monooxygenase required for bisfuran desaturation during aflatoxin/sterigmatocystin biosynthesis. J Biol Chem 272:1589–1594

    Article  CAS  PubMed  Google Scholar 

  • Keller NP, Hohn TM (1997) Metabolic pathway gene clusters in filamentous fungi. Fungal Genet Biol 21:17–29

    Article  CAS  PubMed  Google Scholar 

  • Keller NP, Cleveland TE, Bhatnagar D, Cleveland TE, Ullah AHJ (1993) Purification of a 40-kilodalton methyltransferase active in the aflatoxin biosynthetic pathway. Appl Environ Microbiol 59:479–484

    CAS  PubMed  Google Scholar 

  • Keller NP, Segner S, Bhatnagar D, Adams TH (1995) stcS, a putative P-450 monooxygenase, is required for the conversion of versicolorin A to sterigmatocystin in Aspergillus nidulans. Appl Environ Microbiol 61:3628–3632

    CAS  PubMed  Google Scholar 

  • Keller NP, Watanabe CMH, Kelker HS, Adams TH, Townsend CA (2000) Requirement of monooxygenase-mediated steps for sterigmatocystin biosynthesis by Aspergillus nidulans. Appl Environ Microbiol 66:359–362

    Google Scholar 

  • Kennedy J, Auclar A, Kendrew SG, Park C, Vederas JC, Hutchinson CR (1999) Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284:1368–1372

    Article  CAS  PubMed  Google Scholar 

  • Koreeda M, Hulin B, Yoshihara M, Townsend CA, Christensen SB (1985) Synthesis and absolute configuration of (+)-averufin. J Org Chem 50:5426–5428

    CAS  Google Scholar 

  • Kusumoto KI, Hsieh DPH (1996) Purification and characterization of the esterases involved in aflatoxin biosynthesis in Aspergillus parasiticus. Can J Microbiol 42:804–810

    Google Scholar 

  • Lee L-W, Chiou C-H, Linz JE (2002) Function of native OmtA in vivo and expression and distribution of this protein in colonies of Aspergillus parasiticus. Appl Environ Microbiol 68:5718–5727

    CAS  PubMed  Google Scholar 

  • Liang SH, Skory CD, Linz JE (1996) Characterization of the function of the ver-1A and ver-1B genes involved in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 62:4568–4575

    CAS  PubMed  Google Scholar 

  • Lin BK, Anderson JA (1992) Purification and properties of versiconal cyclase from Aspergillus parasiticus. Arch Biochem Biophys 293:67–70

    CAS  PubMed  Google Scholar 

  • Maggon KK, Gupta SK, Venkitasubramanian TA (1977) Biosynthesis of aflatoxins Bacteriol Rev 41:822–855

    CAS  Google Scholar 

  • Mahanti N, Bhatnagar D, Cary JW, Joubran J, Linz JE (1996) Structure and function of fas-1A, a gene encoding a putative fatty acid synthase directly involved in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 62:191–195

    CAS  PubMed  Google Scholar 

  • Massey TE, Stewart RK, Daniels JM, Liu L (1995) Biochemical and molecular aspects of mammalian susceptibility to aflatoxin B1 carcinogenicity. Proc Soc Exp Bio Med 2003:2213–227

    Google Scholar 

  • 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

    CAS  Google Scholar 

  • McCormick SP, Bhatnagar D, Lee LS (1987) Averufanin is an aflatoxin B1 precursor between averantin and averufin in the biosynthetic pathway. Appl Environ Microbiol 53:14–16

    CAS  PubMed  Google Scholar 

  • McGuire SM, Silva JC, Casillas EG, Townsend CA (1996) Purification and characterization of versicolorin B synthase from Aspergillus parasiticus. Catalysis of the stereodifferentiating cyclization in aflatoxin biosynthesis essential to DNA interaction Biochem 35:11470–11486

    Article  CAS  Google Scholar 

  • Meyers DM, O’Brian G, Du WL, Bhatnagar E, Payne GA (1998) Characterization of aflJ, a gene required for conversion of pathway intermediates to aflatoxin. Appl Environ Microbiol 64:3713–3717

    CAS  PubMed  Google Scholar 

  • Minto RE, Townsend CA (1997) Enzymology and molecular biology of aflatoxin biosynthesis. Chem Rev 97:2537–2555

    Article  CAS  Google Scholar 

  • Miyamoto M, Matsumoto J, Iwaya T, Itagaki E (1995) Bacterial steroid monooxygenase catalyzing the Baeyer-Villiger oxidation of C21-ketosteroids from Rhodococcus rhodochrous: the isolation and characterization. Biochim Biophys Acta 1251:115–124

    Article  CAS  PubMed  Google Scholar 

  • Motomura M, Chihaya N, Shinozawa T, Hamasaki T, Yabe K (1999) Cloning and characterization of the O-methyltransferase I gene (dmtA) from Aspergillus parasiticus associated with the conversion of demethylsterigmatocystin to sterigmatocystin and dihydrodemethylsterigmatocystin to dihydrosterigatocystin in aflatoxin biosynthesis. Appl Environ Microbiol 65:4987–4994

    CAS  PubMed  Google Scholar 

  • Payne GA (1998) Aflatoxin in maize. Crit Rev Plant Sci 10:423–440

    Google Scholar 

  • Payne GA, Brown MP (1998) Genetics and physiology of aflatoxin biosynthesis. Annu Rev Phytopathol 36:329–362

    Article  CAS  Google Scholar 

  • Payne GA, Nystrom 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

    CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Robens J (2001) The costs of mycotoxin management to the USA: management of aflatoxins in the United States. http://www.apsnet.org/online/feature/mycotoxin/top.html

  • Sakuno E, Yabe K, Nakajima H (2003) 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 69:6418–6426

    Article  CAS  PubMed  Google Scholar 

  • Schroeder HW, Cole RS, Grigsby RD, Hein HJ (1974) Inhibition of aflatoxin production and tentative identification of an aflatoxin intermediate “versiconol acetate” from treatment with dichlorvos. Appl Microbiol 27:394–399

    CAS  PubMed  Google Scholar 

  • Silva JC, Townsend CA (1996) Heterologous expression, isolation, and characterization of versicolorin B synthase from Aspergillus parasiticus. J Biol Chem 272:804–813

    Article  Google Scholar 

  • Silva JC, Minto RE, Barry III CE, Holland KA, Townsend CA (1996) Isolation and characterization of the versicolorin B synthase gene from Aspergillus parasiticus: expression of the aflatoxin B1 biosynthetic cluster. J Biol Chem 271:13600–13608

    Article  CAS  PubMed  Google Scholar 

  • 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

    Google Scholar 

  • Townsend CA, Christensen SB, Trautwein K (1984) Hexanoate as a starter unit in polyketide synthesis. J Am Chem Soc 106:3868–3869

    CAS  Google Scholar 

  • Townsend CA, Plavcan KA, Pal K, Brobst SW, Irish MS, Ely EW, Bennett JW (1988a) Hydroxyversicolorone: Isolation and characterization of a potential intermediate in aflatoxin biosynthesis. J Org Chem 53:2472–2477

    CAS  Google Scholar 

  • Townsend CA, Whittamore PRO, Brobst SW (1988b) Hydroxyversicolorone: synthesis and incorporation of a new intermediate in aflatoxin biosynthesis. J Chem Soc Chem Commun 726–728

  • Trail F, Chang PK, Cary J, Linz J (1994) Structural and functional analysis of the nor-1 gene involved in the biosynthesis of aflatoxins by Aspergillus parasticus. Appl Environ Microbiol 60:4078–4085

    CAS  PubMed  Google Scholar 

  • Trail F, Mahanti N, Rarick M, Mehigh MR, Liang SH, Zhou R, Linz J (1995a) 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

    CAS  PubMed  Google Scholar 

  • Trail F, Mahanti N, Linz J (1995b) Molecular biology of aflatoxin biosynthesis. Microbiol 141:755–765

    CAS  PubMed  Google Scholar 

  • Watanabe CMH, Townsend CA (2002) Initial characterization of a type I fatty acid synthase and polyketide synthase multienzyme complex NorS in the biosynthesis of aflatoxin B (1). Chem Biol 9:981–988

    Article  CAS  PubMed  Google Scholar 

  • Watanabe CMH, Wilson D, Linz JE, Townsend CA (1996) Demonstration of the catalytic roles and evidence for the physical association of type I fatty acid syntheses and a polyketide synthase in the biosynthesis of aflatoxin B1. Chem Biol 3:463–469

    CAS  PubMed  Google Scholar 

  • Woloshuk CP, Prieto R (1998) Genetic organization and function of the aflatoxin B1 biosynthetic genes. FEMS Microbiol Lett 160:169–176

    Article  CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Yabe K (2002) Pathway and genes of aflatoxin biosynthesis. In: Fierro F, Francisco J (eds) Microbial secondary metabolites: biosynthesis, genetics and regulation, Research Signpost. India, pp 227–251

  • Yabe K, Hamasaki T (1993) Stereochemistry during aflatoxin biosynthesis: cyclase reaction in the conversion of versiconal to versicolorin B and racemization of versiconal hemiacetal acetate. Appl Environ Microbiol 59:2493-2500

    CAS  PubMed  Google Scholar 

  • Yabe K, Ando Y, Hamasaki T (1988) Biosynthetic relationship among aflatoxins B1, B2, G1, and G2. Appl Environ Microbiol 54:2101–2106

    CAS  PubMed  Google Scholar 

  • Yabe K, Ando Y, Hashimoto J, Hamasaki T (1989) Two distinct O-metyltransferases in aflatoxin biosynthesis. Appl Environ Microbiol 55:2172–2177

    CAS  PubMed  Google Scholar 

  • Yabe K, Ando Y, Hamasaki T (1991a) A metabolic grid among versiconal hemiacetal acetate, versiconol acetate, versiconol and versiconal during aflatoxin biosynthesis. J Gen Microbiol 137:2469–2475

    CAS  PubMed  Google Scholar 

  • Yabe K, Ando Y, Hamasaki T (1991b) Desaturase activity in the branching step between aflatoxins B1 and G1 and aflatoxins B2 and G2, Agric Biol Chem 55:1907–1911

    Google Scholar 

  • Yabe K, Nakamura Y, Nakajima H, Ando Y, Hamasaki T (1991c) Enzymatic conversion of norsolorinic acid to averufin in aflatoxin biosynthesis. Appl Environ Microbiol 57:1340–1345

    CAS  PubMed  Google Scholar 

  • Yabe K, Matsuyama Y, Ando Y, Nakajima H, Hamasaki T (1993) Stereochemistry during aflatoxin biosynthesis: conversion of norsolorinic acid to averufin. Appl Environ Microbiol 59:2486–2492

    CAS  PubMed  Google Scholar 

  • Yabe K, Matsushima KI, Koyama T, Hamasaki T (1998) Purification and characterization of O-metyltransferase I involved in conversion of demethylsterigmatocystin to sterigmatocystin and dihydrodemethylsterigamtocsytin to dihydroserimgmatocystin during aflatoxin biosynthesis Appl Environ Microbiol 64:166–171

    Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Yabe K, Chihaya N, Hamamatsu S, Sakuno E, Hamasaki T, Nakajima H, Bennett JW (2003) Enzymatic conversion of averufin to hydroxyversicolorone and elucidation of a novel metabolic grid involved in aflatoxin biosynthesis. Appl Environ Microbiol 69:66–73

    Article  CAS  PubMed  Google Scholar 

  • Yao RC, Hsieh DPH (1974) Step of dichlorvos inhibition in the pathway of aflatoxin biosynthesis. Appl Microbiol 28:52–57

    CAS  PubMed  Google Scholar 

  • Yu JH, Leonard TJ (1995) Sterigmatocystin biosynthesis in Aspergillus nidulans required a novel type I polyketide synthetase. J Bacteriol 177:4792–4800

    CAS  PubMed  Google Scholar 

  • Yu J, Cary JW, Bhatnagar D, Cleveland TE, Keller NP, Chu FS (1993) Cloning and characterization of a cDNA from Aspergillus parasiticus encoding an O-methyltransferase involved in aflatoxin biosynthesis. Appl Environ Microbiol 59:3564–3571

    CAS  PubMed  Google Scholar 

  • Yu JH, Butchko RAE, 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 Gent 29:549–555

    Article  CAS  Google Scholar 

  • Yu J, Chang PK, 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 Microbiol Biotechnol 63:1349–1356

    CAS  Google Scholar 

  • Yu J, Chang PK, Ehrlich KC, Cary JW, Montalbano B, Dyer JM, Bhatnagar D, Cleveland TE (1998) Characterization of the critical amino acids of an Aspergillus parasiticus cytochrome P450 monooxygenase encoded by ordA involved in aflatoxin B1, G1, B2, and G2 biosynthesis Appl Environ Microbiol 64:4834–4841

    Google Scholar 

  • Yu J, Woloshuk CP, Bhatnagar D, Cleveland TE (2000a) Cloning and characterization of avfA and omtB genes involved in aflatoxin biosynthesis in three Aspergillus species. Gene 248:157–167

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Chang PK, Bhatnagar D, Cleveland TE (2000b) 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

    Google Scholar 

  • Yu J, Chang PK, Bhatnagar D, Cleveland TE (2003) Cloning and functional expression of an esterase gene in Aspergillus parasiticus. Mycopathologia 156:227–234

    Article  CAS  Google Scholar 

  • Zhou R, Linz JE (1999) Enzymatic function of the Nor-1 protein in aflatoxin biosynthesis in Aspergillus parasiticus. Appl Environ Microbiol 65:5639–5641

    Google Scholar 

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Acknowledgements

We would like to dedicate this review to the late Professor Takashi Hamasaki, Tottori University, Japan, who contributed greatly to our research. This work was supported in part by a Grant-in-Aid (Bio Design Program) from the Ministry of Agriculture, Forestry and Fisheries of Japan (BDP-03-VI-5).

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  1. National Food Research Institute, Tsukuba, 305-8642, Ibaraki, Japan

    K. Yabe

  2. Faculty of Agriculture, Tottori University, 680-8553, Tottori, Japan

    H. Nakajima

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Yabe, K., Nakajima, H. Enzyme reactions and genes in aflatoxin biosynthesis. Appl Microbiol Biotechnol 64, 745–755 (2004). https://doi.org/10.1007/s00253-004-1566-x

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