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Mycopathologia

, Volume 162, Issue 3, pp 201–213 | Cite as

Biosynthesis of dothistromin

  • Rosie E. Bradshaw
  • Shuguang Zhang
Article

Abstract

Dothistromin is a mycotoxin that is remarkably similar in structure to versicolorin B, a precursor of both aflatoxin and sterigmatocystin. Dothistromin-producing fungi also produce related compounds, including some aflatoxin precursors as well as alternative forms of dothistromin. Dothistromin is synthesized by pathogenic species of Dothistroma in the red bands of pine needles associated with needle blight, but is also made in culture where it is strongly secreted into the surrounding medium. Orthologs of aflatoxin and sterigmatocystin biosynthetic genes have been found that are required for the biosynthesis of dothistromin, along with others that are speculated to be involved in the same pathway on the basis of their sequence similarity to aflatoxin genes. An epoxide hydrolase gene that has no homolog in the aflatoxin or sterigmatocystin gene clusters is also clustered with the dothistromin genes, and all these genes appear to be located on a minichromosome in Dothistroma septosporum. The dothistromin genes are expressed at an early stage of growth, suggesting a role in the first stages of plant invasion by the fungus. Future studies are expected to reveal more about the role of dothistromin in needle blight and about the genomic organization and expression of dothistromin genes: these studies will provide for interesting comparisons with these aspects of aflatoxin and sterigmatocystin biosynthesis.

Keywords

aflatoxin Dothistroma needle blight epoxide hydrolase gene cluster mycotoxin sterigmatocystin 

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References

  1. 1.
    Bradshaw, RE 2004Dothistroma (red-band) needle blight of pines and the dothistromin toxin: a reviewFor Pathol34163185Google Scholar
  2. 2.
    Woods, AJ, Coates, KD, Hamann, A 2005Is an unprecedented Dothistroma needle blight epidemic related to climate change?Bioscience55761769CrossRefGoogle Scholar
  3. 3.
    Bassett C, Buchanan M, Gallagher RT, Hodges R. A toxic difuroanthraquinone from Dothistroma pini. Chem Ind (London) 1970; 1659–1660Google Scholar
  4. 4.
    Assante, G, Locci, R, Camarada, L, Merlini, L, Nasini, G. 1977Screening of the genus Cercospora for secondary metabolitesPhytochemistry16243247CrossRefGoogle Scholar
  5. 5.
    Shain, L, Franich, RA 1981Induction of Dothistroma blight symptoms with dothistrominPhysiol. Plant Pathol.194955Google Scholar
  6. 6.
    Gallagher, RT, Hodges, R 1972The chemistry of dothistromin, a difuroanthraquinone from Dothistroma pini Aust J Chem2523992407CrossRefGoogle Scholar
  7. 7.
    Bear CA, Waters JM, Waters TN. Crystal structure and absolute configuration of a derivative of dothistromin, a fungal toxin implicated in pine-needle blight. J Chem Soc Perkin Trans II 1972; 2375–2378Google Scholar
  8. 8.
    Assante, G, Camarda, L, Merlini, L, Nasini, G. 1977Dothistromin and 2-epidothistromin from Cercospora smilacis Phytochemistry16125126CrossRefGoogle Scholar
  9. 9.
    Assante, G 1985Isolation and characterization of new dothstromins from Mycosphaerella laricina hartPhytopathol Mediterr24271273Google Scholar
  10. 10.
    Gadgil, PD 1967Infection of Pinus radiata needles by Dothistroma pini N Z J. Bot.5498503Google Scholar
  11. 11.
    Debnam, P, Narayan, R, Cranshaw, N, Jones, WT, Nicol, M, Reynolds, PHS 1994Role of the fungal toxin dothistromin in resistance towards Dothistroma needle blight in Pinus radiataProceedings of the American Society of Plant Physiologists Annual MeetingPortland, OregonGoogle Scholar
  12. 12.
    Franich, RA, Carson, MJ, Carson, SD 1986Synthesis and accumulation of benzoic acid in Pinus radiata needles in response to tissue injury by dothistromin, and correlation with resistance of P. radiata families to Dothistroma pini Physiol Mol Plant Pathol28267286Google Scholar
  13. 13.
    Edwards, DW, Walker, J 1978Dothistroma needle blight in AustraliaAust For Res8125137Google Scholar
  14. 14.
    Jones, WT, Harvey, D, Jones, SD, Fielder, S, Debnam, P, Reynolds, PHS 1993Competitive ELISA employing monoclonal antibodies specific for dothistrominFood Agric Immunol5187197Google Scholar
  15. 15.
    Bradshaw, RE, Ganley, RJ, Jones, WT, Dyer, PS 2000High levels of dothistromin toxin produced by the forest pathogen Dothistroma pini Mycol Res104325332CrossRefGoogle Scholar
  16. 16.
    Barnes, I, Crous, PW, Wingfield, BD, Wingfield, MJ 2004Multigene phylogenies reveal that red band needle bight of Pinus is caused by two distinct species of Dothistroma, D. septosporum and D. pini Stud Mycol50551565Google Scholar
  17. 17.
    Gallagher RT. The structure of dothistromin. (Dissertation). Massey University, Palmerston North, New Zealand, 1971Google Scholar
  18. 18.
    Horn, BW, Dorner, JW 2001Effect of competition and adverse culture conditions on aflatoxin production by Aspergillus flavus through successive generationsMycologia94741751Google Scholar
  19. 19.
    Danks, AV, Hodges, R 1974Polyhydroxyanthraquinones from Dothistroma pini Aust J Chem2716031606CrossRefGoogle Scholar
  20. 20.
    Shaw, GJ, Chick, M, Hodges, RA 197813C NMR study of the biosynthesis of the anthraquinone dothistromin by Dothistroma piniPhytochemistry1717431745CrossRefGoogle Scholar
  21. 21.
    Bradshaw, RE, Bhatnagar, D, Ganley, RJ, Gillman, CJ, Monahan, BJ, Seconi, JM 2002Dothistroma pini, a forest pathogen, contains homologs of aflatoxin biosynthetic pathway genesAppl Environ Microbiol6828852892PubMedCrossRefGoogle Scholar
  22. 22.
    Henry, KM, Townsend, CA 2005Ordering the reductive and cytochrome P450 oxidative steps in demethylsterigmatocystin formation yields general insights into the biosynthesis of aflatoxin and related fungal metabolitesJ Am Chem Soc12737243733PubMedCrossRefGoogle Scholar
  23. 23.
    Chang, P-K, Cary, JW, Yu, J, Bhatnagar, D, Cleveland, TE 1995The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesisMol Gen Genet248270277PubMedCrossRefGoogle Scholar
  24. 24.
    Feng, GH, Leonard, TJ 1995Characterization of the polyketide synthase gene (pksL1) required for aflatoxin biosynthesis in Aspergillus parasiticus J Bacteriol17762466254PubMedGoogle Scholar
  25. 25.
    Yu, J, Chang, P-K, Ehrlich, KC, Cary, JW, Bhatnagar, D, Cleveland, TE, Payne, GA, Linz, JE, Woloshuk, CP, Bennett, JW 2004Clustered pathway genes in aflatoxin biosynthesisAppl. Environ. Microbiol.7012531262PubMedCrossRefGoogle Scholar
  26. 26.
    Brown, DW, Yu, J-H, Kelkar, HS, Fernandes, M, Nesbitt, TC, Keller, NP, Adams, TH, Leonard, TJ 1996Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans Proc Natl Acad Sci USA9314181422PubMedCrossRefGoogle Scholar
  27. 27.
    Zhang Y, Keller N, Tsitsigiannis D. Secondary metabolite gene clusters. In: An Z, ed. Handbook of Industrial Mycology, Marcel Dekker, New York, 2005: 355–385Google Scholar
  28. 28.
    Chang, P-K, Yu, J, Yu, J-H 2004aflT, a MFS transporter-encoding gene located in the aflatoxin gene cluster, does not have a significant role in aflatoxin secretionFungal Genet. Biol.41911920PubMedCrossRefGoogle Scholar
  29. 29.
    Martin, JF, Casqueiro, J, Liras, P 2005Secretion systems for secondary metabolites: How producer cells send out messages of intercellular communicationCurr Opin Microbiol8282293PubMedCrossRefGoogle Scholar
  30. 30.
    Yu, J, Woloshuk, CP, Bhatnagar, D, Cleveland, TE 2000Cloning and characterization of avfA and omtB genes involved in aflatoxin biosynthesis in three Aspergillus speciesGene248157167PubMedCrossRefGoogle Scholar
  31. 31.
    Yabe, K, Chihaya, N, Hamamatsu, S, Sakuno, E, Hamasaki, T, Nakajima, H, Bennett, JW 2003Enzymatic conversion of averufin to hydroxyversicolorone and elucidation of a novel metabolic grid involved in aflatoxin biosynthesisAppl Environ Microbiol696673PubMedCrossRefGoogle Scholar
  32. 32.
    Wen, Y, Hatabayashi, H, Arai, H, Kitamoto, K, Yabe, K 2005Function of the cypX and moxY genes in aflatoxin biosynthesis in Aspergillus parasiticus Appl Environ Microbiol7131923198PubMedCrossRefGoogle Scholar
  33. 33.
    Yu, J, Chang, P-K, Bhatnagar, D, Cleveland, TE 2000Genes encoding cytochrome P450 and monooxygenase enzymes define one end of the aflatoxin pathway gene cluster in Aspergillus paraciticus Appl Microbiol Biotechnol53583590PubMedCrossRefGoogle Scholar
  34. 34.
    Sakuno, E, Wen, Y, Hatabayashi, H, Arai, H, Aoki, C, Yabe, K, Nakajima, H 2005Aspergillusparasiticus cyclase catalyzes two dehydration steps in aflatoxin biosynthesisAppl Environ Microbiol7129993006PubMedCrossRefGoogle Scholar
  35. 35.
    Arand, M, Hemmer, H, Durk, H, Baratti, J, Archelas, A, Furtoss, R, Oesch, F 1999Cloning and molecular characterization of a soluble epoxide hydrolase from Aspergillus niger that is related to mammalian microsomal epoxide hydrolaseBiochem J344273280PubMedCrossRefGoogle Scholar
  36. 36.
    Kelly, EJ, Erickson, KE, Sengstag, C, Eaton, DL 2002Expression of human microsomal epoxide hydrolase in Saccharomyces cerevisiae reveals a functional role in aflatoxin B1 detoxificationToxicol Sci653542PubMedCrossRefGoogle Scholar
  37. 37.
    Coyle, CM, Panaccione, DG 2005An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus Appl Environ Microbiol7131123118PubMedCrossRefGoogle Scholar
  38. 38.
    Covert, SF 1998Supernumerary chromosomes in filamentous fungiCurr. Genet.33311319PubMedCrossRefGoogle Scholar
  39. 39.
    Hatta, R, Ito, K, Hosaki, Y, Tanaka, T, Tanaka, A, Yamamoto, M, Akimitsu, K, Tsuge, T 2002A conditionally dispensable chromosome controls host-specific pathogenicity in the fungal plant pathogen Alternaria alternata Genetics1615970PubMedGoogle Scholar
  40. 40.
    Skory, CD, Chang, P, Linz, JE 1993Regulated expression of the nor-1 and ver-1 genes associated with aflatoxin biosynthesisAppl Environ Microbiol5916421646PubMedGoogle Scholar
  41. 41.
    Feng, GH, Leonard, TJ 1998Culture conditions control expression of the genes for aflatoxin and sterigmatocystin biosynthesis in Aspergillus parasiticus and Aspergillus nidulans Appl Environ Microbiol6422752277PubMedGoogle Scholar
  42. 42.
    Cotty, PJ 1988Aflatoxin and sclerotial production by Aspergillus flavus: Influence of pHPhytopathology7812501253Google Scholar
  43. 43.
    Morrice, J, MacKenzie, DA, Parr, AJ, Archer, DB 1998Isolation and characterization of the acetyl-CoA carboxylase gene from Aspergillus nidulans Curr Genet34379385PubMedCrossRefGoogle Scholar
  44. 44.
    Keller, NP, Nesbitt, C, Sarr, B, Phillips, TD, Burow, GB 1997pH regulation of sterigmatocystin and aflatoxin biosynthesis in Aspergillus sppPhytopathology87643648PubMedGoogle Scholar
  45. 45.
    Ivory, MH 1967Spore germination and growth in culture of Dothistroma pini var keniensis Trans Br Mycol Soc50563572CrossRefGoogle Scholar
  46. 46.
    Ehrlich, KC, Montalbano, BG, Cotty, PJ 2003Sequence comparison of aflR from different Aspergillus species provides evidence for variability in regulation of aflatoxin productionFungal Genet Biol386374PubMedCrossRefGoogle Scholar
  47. 47.
    Calvo, AM, Wilson, RA, Bok, JW, Keller, NP 2002Relationship between secondary metabolism and fungal developmentMicrobiol Mol Biol Rev66447459PubMedCrossRefGoogle Scholar
  48. 48.
    Ehrlich, KC, Montalbano, BG, Cary, JW, Cotty, PJ 2002Promoter elements in the aflatoxin pathway polyketide synthase geneBiochim. Biophys Acta1576171175PubMedGoogle Scholar
  49. 49.
    Ehrlich, KC, Cotty, PJ 2002Variability in nitrogen regulation of aflatoxin production by Aspergillus flavus strainsAppl Microbiol Biotechnol60174178PubMedCrossRefGoogle Scholar
  50. 50.
    Hicks, JK, Yu, J-H, Keller, NP, Adams, TH 1997Aspergillus sporulation and mycotoxin production both require inactivation of the FadA Gα protein-dependent signaling pathwayEMBO J.1649164923PubMedCrossRefGoogle Scholar
  51. 51.
    Weiergang, I, Wood, KV, Dunkle, LD, Nicholson, RL 2004In vivo growth and pathotoxin production by the maize pathogen Cochliobolus carbonumPhysiol Mol Plant Pathol64273279CrossRefGoogle Scholar
  52. 52.
    Nishimura, S, Scheffer, RP 1965Interactions between Helminthosporium victoriae spores and oat tissuePhytopathology55629634Google Scholar
  53. 53.
    Comstock, JC, Martinson, CA 1975Involvement of Helminthosporium maydis race T toxin during colonization of maize leavesPhytopathology65616619CrossRefGoogle Scholar
  54. 54.
    Tag, A, Hicks, J, Garifullina, G, Ake, CJ, Phillips, TD, Beremand, M, Keller, N 2000G-protein signalling mediates differential production of toxic secondary metabolitesMol Microbiol38658665PubMedCrossRefGoogle Scholar
  55. 55.
    Shaner, G, Stromberg, EL, Lacy, GH, Barker, KR, Pirone, TP 1992Nomenclature and concepts of pathogenicity and virulenceAnnu Rev Phytopathol304766CrossRefPubMedGoogle Scholar
  56. 56.
    Youngman RJ, Elstner EF Photodynamic and reductive mechanisms of oxygen activation by the fungal phytotoxins, cercosporin and dothistromin. In: Bors W, Saran M, Tait D, eds. Oxygen Radicals in Chemistry and Biology, Walter de Gruyter and Co., Berlin, 1984: 501–508Google Scholar
  57. 57.
    Harvey, AM, Batt, RD, Pritchard, GG 1976Inhibition of RNA synthesis in Chlorella pyrenoidosa and Bacillus megaterium by the pine-blight toxin, dothistrominJ Gen Microbiol96268276PubMedGoogle Scholar
  58. 58.
    Cotty, PJ 1994Influence of field application of an atoxigenic strain of Aspergillus flavus on the populations of A. flavus infecting cotton bolls and on the aflatoxin content of cottonseedPhytopathology8412701277Google Scholar
  59. 59.
    Dorner, JW, Cole, RJ, Wicklow, DT 1999Aflatoxin reduction in corn through field application of competitive fungiJ Food Prot62650656PubMedGoogle Scholar
  60. 60.
    Wilkinson, HH, Ramaswamy, A, Sim, SC, Keller, NP 2004Increased conidiation associated with progression along the sterigmatocystin biosynthetic pathwayMycologia9611901198Google Scholar
  61. 61.
    Malz, S, Grell, MN, Thrane, C, Maier, FJ, Rosager, P, Felk, A, Albertsen, KS, Salomon, S, Bohn, L, Schafer, W, Giese, H 2005Identification of a gene cluster responsible for the biosynthesis of aurofusarin in the Fusarium graminearum species complexFungal Genet Biol42420433PubMedCrossRefGoogle Scholar
  62. 62.
    Bradshaw RE, Jin H-P, Morgan BS, Schwelm A, Teddy OR, Young CA, Zhang SG. A polyketide synthase gene required for biosynthesis of the aflatoxin-like toxin, dothistromin. Mycopathologia 2006; 161: 283–294Google Scholar

Copyright information

© Springer 2006

Authors and Affiliations

  1. 1.National Centre for Advanced Bio-Protection TechnologiesInstitute of Molecular BioSciences, Massey UniversityPalmerston NorthNew Zealand

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