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Aflatoxin-like Gene Clusters and How They Evolved

  • Kenneth C. Ehrlich
  • Jiujiang YuEmail author
Chapter

Abstract

Almost all filamentous fungi produce one or more polyketide -derived secondary metabolites (Demain and Fang 2000). The most common secondary metabolite is 1,4-dihydroxynaphthoquinone, the precursor of melanin. Others are precursors of fungal pigment s or are toxic to plants, animals, or soil microorganisms. Their toxicity often is used defensively by the fungus against competing organisms, or offensively, by facilitating invasion of plants. The best studied of the polyketide s are the bis-furans known collectively as aflatoxin s (AF). In this chapter, we will discuss current knowledge concerning the AF gene cluster and how such clusters evolved. Two types of gene cluster s are found in known isolates of AF-producing fungi. These differ mainly in the order of the genes (Fig. 5.1). AF-producing species such as A. flavus and A. parasiticus have the gene cluster shown in Fig. 5.1a, while the newly discovered Aspergillus species, ochraceoroseus, astellata and venezuelensis, have a gene cluster similar to that of the ST-producing species A. nidulans (Fig. 5.1b) (Cary and Ehrlich 2006). Two genes in the cluster (aflR and aflJ) encode proteins involved in transcriptional activation of most of the other structural genes (Chang 2003, 2004).

Keywords

Gene Cluster Subtelomeric Region Biosynthesis Cluster Starter Unit Secondary Metabolite Gene Cluster 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Berbee ML, Taylor JW (2001) Fungal molecular evolution: gene trees and geologic time. In: McLaughlin DJ, McLaughlin E, Lemke PA (eds) The mycota. Springer, Berlin, pp 229–246Google Scholar
  2. Bok JW, Noordermeer D, Kale SP, Keller NP (2006) Secondary metabolic gene cluster silencing in Aspergillus nidulans. Mol Microbiol 61:1636–1645PubMedCrossRefGoogle Scholar
  3. Bouhired S, Weber M, Kempf-Sontag A, Keller NP, Hoffmeister D (2007) Accurate prediction of the Aspergillus nidulans terrequinone gene cluster boundaries using the transcriptional regulator LaeA. Fungal Genet Biol 44:1134–1145PubMedCrossRefGoogle Scholar
  4. 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 68:2885–2892PubMedCrossRefGoogle Scholar
  5. Bradshaw RE, Zhang S (2006) Biosynthesis of dothistromin. Mycopathologia 162:201–213PubMedCrossRefGoogle Scholar
  6. Calvo AM, Wilson RA, Bok JW, Keller NP (2002) Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev 66:447–459PubMedCrossRefGoogle Scholar
  7. Carbone I, Ramirez-Prado JH, Jakobek JL, Horn BW (2007) Gene duplication, modularity and adaptation in the evolution of the aflatoxin gene cluster. BMC Evol Biol 7:111, doi:110.1186/1471–2148–1187–1111PubMedCrossRefGoogle Scholar
  8. Cary J, Ehrlich K (2006) Aflatoxigenicity in Aspergillus: molecular genetics, phylogenetic relationships and evolutionary implications. Mycopathologia 162:167–177PubMedCrossRefGoogle Scholar
  9. Chang PK (2003) The Aspergillus parasiticus protein AFLJ interacts with the aflatoxin pathway-specific regulator AFLR. Mol Genet Genomics 268:711–719PubMedGoogle Scholar
  10. Chang PK (2004) Lack of interaction between AFLR and AFLJ contributes to nonaflatoxigenicity of Aspergillus sojae. J Biotechnol 107:245–253PubMedCrossRefGoogle Scholar
  11. Chang PK, Horn BW, Dorner JW (2005) Sequence breakpoints in the aflatoxin biosynthesis gene cluster and flanking regions in nonaflatoxigenic Aspergillus flavus isolates. Fungal Genet Biol 42:914–923PubMedCrossRefGoogle Scholar
  12. Chiou CH, Miller M, Wilson DL, Trail F, Linz JE (2002) Chromosomal location plays a role in regulation of aflatoxin gene expression in Aspergillus parasiticus. Appl Environ Microbiol 68:306–315PubMedCrossRefGoogle Scholar
  13. Cotty PJ, Bayman DS, Egel DS, Elias KS (1994) Agriculture, aflatoxins and Aspergillus. In: Powell K (ed) The genus Aspergillus. Plenum, New York, pp 1–27Google Scholar
  14. Demain AL, Fang A (2000) The natural functions of secondary metabolites. Adv Biochem Eng Biotechnol 69:1–39PubMedGoogle Scholar
  15. Ehrlich KC, Cary JW, Montalbano BG (1999) Characterization of promoter elements involved in the expression of early and late aflatoxin pathway genes. In: Twentieth Fungal Genetics Conference, vol 46. Fungal Genetics Newsletter, Asilomar Conference Center, Pacific Grove, CA, p 45 (Abst 28)Google Scholar
  16. Ehrlich KC, Cotty PJ (2004) An isolate of Aspergillus flavus used to reduce aflatoxin contamination in cottonseed has a defective polyketide synthase. Appl Microbiol Biotechnol 65:473–478PubMedCrossRefGoogle Scholar
  17. Foster PL (2000) Adaptive mutation: implications for evolution. Bioessays 22:1067–1074PubMedCrossRefGoogle Scholar
  18. Galagan JE, Calvo SE, Cuomo C, Ma LJ, Wortman JR, Batzoglou S, Lee SI, Basturkmen M, Spevak CC, Clutterbuck J, Kapitonov V, Jurka J, Scazzocchio C, Farman M, Butler J, Purcell S, Harris S, Braus GH, Draht O, Busch S, D'Enfert C, Bouchier C, Goldman GH, Bell-Pedersen D, Griffiths-Jones S, Doonan JH, Yu J, Vienken K, Pain A, Freitag M, Selker EU, Archer DB, Penalva MA, Oakley BR, Momany M, Tanaka T, Kumagai T, Asai K, Machida M, Nierman WC, Denning DW, Caddick M, Hynes M, Paoletti M, Fischer R, Miller B, Dyer P, Sachs MS, Osmani SA, Birren BW (2005) Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature 438:1105–1115PubMedCrossRefGoogle Scholar
  19. Gomez BL, Nosanchuk JD (2003) Melanin and fungi. Curr Opin Infect Dis 16:91–96PubMedCrossRefGoogle Scholar
  20. Heckman DS, Geiser DM, Eidell BR, Stauffer RL, Kardos NL, Hedges SB (2001) Molecular evidence for the early colonization of land by fungi and plants. Science 293:1129–1133PubMedCrossRefGoogle Scholar
  21. Henson JM, Butler MJ, Day AW (1999) The dark side of the mycelium: melanins of phytopathogenic fungi. Annu Rev Phytopathol 37:447–471PubMedCrossRefGoogle Scholar
  22. 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 16:4916–4923PubMedCrossRefGoogle Scholar
  23. Hoffmeister M, Martin W (2003) Interspecific evolution: microbial symbiosis, endosymbiosis and gene transfer. Environ Microbiol 5:641–649PubMedCrossRefGoogle Scholar
  24. Inagaki A, Takano Y, Kubo Y, Mise K, Furusawa A (2000) Construction of an equalized cDNA library from Colletotrichum lagenarium and its application to the isolation of differentially expressed genes. Can J Biochem 46:150–158Google Scholar
  25. Ito Y, Peterson SW, Wicklow DT, Goto T (2001) Aspergillus pseudotamarii, a new aflatoxin producing species in Aspergillus section Flavi. Mycol Res 105:233–239CrossRefGoogle Scholar
  26. Kasuga T, White TJ, Taylor JW (2002) Estimation of nucleotide substitution rates in eurotiomycete fungi. Mol Biol Evol 19:2318–2324PubMedCrossRefGoogle Scholar
  27. Keller N, Bok J, Chung D, Perrin RM, Keats Shwab E (2006) LaeA, a global regulator of Aspergillus toxins. Med Mycol 44(Suppl):83–85CrossRefGoogle Scholar
  28. Keller NP, Hohn TM (1997) Metabolic pathway gene clusters in filamentous fungi. Fungal Genet Biol 21:17–29CrossRefGoogle Scholar
  29. Kusumoto K, Yabe K, Nogata Y, Ohta H (1998a) Transcript of a homolog of aflR, a regulatory gene for aflatoxin synthesis in Aspergillus parasiticus, was not detected in Aspergillus oryzae strains. FEMS Microbiol Lett 169:303–307PubMedCrossRefGoogle Scholar
  30. Kusumoto KI, Yabe K, Nogata Y, Ohta H (1998b) Aspergillus oryzae with and without a homolog of aflatoxin biosynthetic gene ver-1. Appl Microbiol Biotechnol 50:98–104PubMedCrossRefGoogle Scholar
  31. Lee YH, Tominaga M, Hayashi R, Sakamoto K, Yamada O, Akita O (2006) Aspergillus oryzae strains with a large deletion of the aflatoxin biosynthetic homologous gene cluster differentiated by chromosomal breakage. Appl Microbiol Biotechnol 72:339–345PubMedCrossRefGoogle Scholar
  32. Machida M, Asai K, Sano M, Tanaka T, Kumagai T, Terai G, Kusumoto K, Arima T, Akita O, Kashiwagi Y, Abe K, Gomi K, Horiuchi H, Kitamoto K, Kobayashi T, Takeuchi M, Denning DW, Galagan JE, Nierman WC, Yu J, Archer DB, Bennett JW, Bhatnagar D, Cleveland TE, Fedorova ND, Gotoh O, Horikawa H, Hosoyama A, Ichinomiya M, Igarashi R, Iwashita K, Juvvadi PR, Kato M, Kato Y, Kin T, Kokubun A, Maeda H, Maeyama N, Maruyama J, Nagasaki H, Nakajima T, Oda K, Okada K, Paulsen I, Sakamoto K, Sawano T, Takahashi M, Takase K, Terabayashi Y, Wortman JR, Yamada O, Yamagata Y, Anazawa H, Hata Y, Koide Y, Komori T, Koyama Y, Minetoki T, Suharnan S, Tanaka A, Isono K, Kuhara S, Ogasawara N, Kikuchi H (2005) Genome sequencing and analysis of Aspergillus oryzae. Nature 438:1157–1161PubMedCrossRefGoogle Scholar
  33. Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Davies R, Dyer PS, Farman M, Fedorova N, Feldblyum TV, Fischer R, Fosker N, Fraser A, Garcia JL, Garcia MJ, Goble A, Goldman GH, Gomi K, Griffith-Jones S, Gwilliam R, Haas B, Haas H, Harris D, Horiuchi H, Huang J, Humphray S, Jimenez J, Keller N, Khouri H, Kitamoto K, Kobayashi T, Konzack S, Kulkarni R, Kumagai T, Lafon A, Latge JP, Li W, Lord A, Lu C, Majoros WH, May GS, Miller BL, Mohamoud Y, Molina M, Monod M, Mouyna I, Mulligan S, Murphy L, O'Neil S, Paulsen I, Penalva MA, Pertea M, Price C, Pritchard BL, Quail MA, Rabbinowitsch E, Rawlins N, Rajandream MA, Reichard U, Renauld H, Robson GD, Rodriguez de Cordoba S, Rodriguez-Pena JM, Ronning CM, Rutter S, Salzberg SL, Sanchez M, Sanchez-Ferrero JC, Saunders D, Seeger K, Squares R, Squares S, Takeuchi M, Tekaia F, Turner G, Vazquez de Aldana CR, Weidman J, White O, Woodward J, Yu JH, Fraser C, Galagan JE, Asai K, Machida M, Hall N, Barrell B, Denning DW (2005) Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 438:1151–1156.PubMedCrossRefGoogle Scholar
  34. O'Donnell K, Cigelnik E, Casper HH (1998) Molecular phylogenetic, morphological, and mycotoxin data support re-identification of the Quorn mycoprotein fungus as Fusarium venenatum. Fungal Genet Biol 23:57–67PubMedCrossRefGoogle Scholar
  35. O'Donnell KO, Kistler HC, Tacke BK, Casper HH (2000) Gene genealogies reveal global phylogeographical structure and reproductive isolation among lineages of Fusarium graminearum, the fungus causing wheat scab. Proc Natl Acad Sci U S A 97:7905–7910PubMedCrossRefGoogle Scholar
  36. Owen NL, Hundley N (2004) Endophytes—the chemical synthesizers inside plants. Sci Prog 87:79–99PubMedCrossRefGoogle Scholar
  37. Payne GA, Nierman WC, Wortman JR, Pritchard BL, Brown D, Dean RA, Bhatnagar D, Cleveland TE, Machida M, Yu J (2006) Whole genome comparison of Aspergillus flavus and A. oryzae. Med Mycol 44(Suppl):9–11CrossRefGoogle Scholar
  38. Pel HJ, de Winde JH, Archer DB, Dyer PS, Hofmann G, Schaap PJ, Turner G, de Vries RP, Albang R, Albermann K, Andersen MR, Bendtsen JD, Benen JA, van den Berg M, Breestraat S, Caddick MX, Contreras R, Cornell M, Coutinho PM, Danchin EG, Debets AJ, Dekker P, van Dijck PW, van Dijk A, Dijkhuizen L, Driessen AJ, d'Enfert C, Geysens S, Goosen C, Groot GS, de Groot PW, Guillemette T, Henrissat B, Herweijer M, van den Hombergh JP, van den Hondel CA, van der Heijden RT, van der Kaaij RM, Klis FM, Kools HJ, Kubicek CP, van Kuyk PA, Lauber J, Lu X, van der Maarel MJ, Meulenberg R, Menke H, Mortimer MA, Nielsen J, Oliver SG, Olsthoorn M, Pal K, van Peij NN, Ram AF, Rinas U, Roubos JA, Sagt CM, Schmoll M, Sun J, Ussery D, Varga J, Vervecken W, van de Vondervoort PJ, Wedler H, Wosten HA, Zeng AP, van Ooyen AJ, Visser J, Stam H (2007) Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat Biotechnol 25:221–231PubMedCrossRefGoogle Scholar
  39. Peterson SW (1997) Phylogenetic relationships in Aspergillus based on rDNA sequence analysis. In: Samson RA, Pitt JI (eds) Classification of Penicillium and Aspergillus: integration of modern taxonomic methods. Harwood, Reading, UK, pp 323–356Google Scholar
  40. 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 93:689–703CrossRefGoogle Scholar
  41. Robyr D, Suka Y, Xenarios I, Kurdistani SK, Wang A, Suka N, Grunstein M (2002) Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases. Cell 109:437–446PubMedCrossRefGoogle Scholar
  42. Ronning CM, Fedorova ND, Bowyer P, Coulson R, Goldman G, Kim HS, Turner G, Wortman JR, Yu J, Anderson MJ, Denning DW, Nierman WC (2005) Genomics of Aspergillus fumigatus. Rev Iberoam Micol 22:223–228PubMedCrossRefGoogle Scholar
  43. Roze LV, Arthur AE, Hong SY, Chanda A, Linz JE (2007) The initiation and pattern of spread of histone H4 acetylation parallel the order of transcriptional activation of genes in the aflatoxin cluster. Mol Microbiol 66:713–726PubMedCrossRefGoogle Scholar
  44. Shimizu K, Hicks JK, Huang TP, Keller NP (2003) Pka, Ras and RGS protein interactions regulate activity of AflR, a Zn(II)2Cys6 transcription factor in Aspergillus nidulans. Genetics 165:1095–1104PubMedGoogle Scholar
  45. 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 38:658–665PubMedCrossRefGoogle Scholar
  46. Wilkinson H, Ramaswamy A, Sim SC, Keller NP (2004) Increased conidiation associated with progression along the sterigmatocystin biosynthetic pathway. Mycologia 96:1190–1198PubMedCrossRefGoogle Scholar
  47. Wong S, Wolfe KH (2005) Birth of a metabolic gene cluster in yeast by adaptive gene relocation. Nat Genet 37:777–782PubMedCrossRefGoogle Scholar
  48. Yu J, Chang PK, Ehrlich KC, Cary JW, Bhatnagar D, Cleveland TE, Payne GA, Linz JE, Woloshuk CP, Bennett JW (2004) Clustered pathway genes in aflatoxin biosynthesis. Appl Environ Microbiol 70:1253–1262PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Southern Regional Research Center, ARS, USDANew OrleansUSA

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