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Allergens/Antigens, Toxins and Polyketides of Important Aspergillus Species

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Abstract

The medical, agricultural and biotechnological importance of the primitive eukaryotic microorganisms, the Fungi was recognized way back in 1920. Among various groups of fungi, the Aspergillus species are studied in great detail using advances in genomics and proteomics to unravel biological and molecular mechanisms in these fungi. Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, Aspergillus parasiticus, Aspergillus nidulans and Aspergillus terreus are some of the important species relevant to human, agricultural and biotechnological applications. The potential of Aspergillus species to produce highly diversified complex biomolecules such as multifunctional proteins (allergens, antigens, enzymes) and polyketides is fascinating and demands greater insight into the understanding of these fungal species for application to human health. Recently a regulator gene for secondary metabolites, LaeA has been identified. Gene mining based on LaeA has facilitated new metabolites with antimicrobial activity such as emericellamides and antitumor activity such as terrequinone A from A. nidulans. Immunoproteomic approach was reported for identification of few novel allergens for A. fumigatus. In this context, the review is focused on recent developments in allergens, antigens, structural and functional diversity of the polyketide synthases that produce polyketides of pharmaceutical and biological importance. Possible antifungal drug targets for development of effective antifungal drugs and new strategies for development of molecular diagnostics are considered.

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References

  1. Tillie-Leblond I, Tonnel AB. Allergic bronchopulmonary aspergillosis. Allergy. 2005;60(8):1004–13. Review.

    Article  PubMed  CAS  Google Scholar 

  2. Dagenais TR, Keller NP. Pathogenesis of Aspergillus fumigatus in invasive Aspergillosis. Clin Microbiol Rev. 2009;22(3):447–65. Review.

    Article  PubMed  CAS  Google Scholar 

  3. Bennett JW. Aspergillus: a primer for the novice. Med Mycol. 2009;47(Suppl 1):S5–12.

    Article  PubMed  Google Scholar 

  4. Karaffa L, Sándor E, Fekete E, Szentirmai A. The biochemistry of citric acid accumulation by Aspergillus niger. Acta Microbiol Immunol Hung. 2001;48(3–4):429–40. Review.

    Article  PubMed  CAS  Google Scholar 

  5. Barrios-González J, Miranda RU. Biotechnological production and applications of statins. Appl Microbiol Biotechnol. 2010;85(4):869–83. Review.

    Article  PubMed  CAS  Google Scholar 

  6. Cleveland TE, Nierman WC. Genomics of industrial Aspergilli and comparison with toxigenic relatives. Food Addit Contam A. 2008;25(9):1147–51.

    Article  CAS  Google Scholar 

  7. Bhabhra R, Askew DS. Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol. 2005;43(Suppl 1):S87–93. Review.

    Article  PubMed  CAS  Google Scholar 

  8. Chang YC, Tsai HF, Karos M, Kwon-Chung KJ. THTA, a thermotolerance gene of Aspergillus fumigatus. Fungal Genet Biol. 2004;41(9):888–96.

    Article  PubMed  CAS  Google Scholar 

  9. Hohl TM, Feldmesser M. Aspergillus fumigatus: principles of pathogenesis and host defense. Eukaryot Cell. 2007;6(11):1953–63.

    Article  PubMed  CAS  Google Scholar 

  10. Beauvais A, Monod M, Wyniger J, Debeaupuis JP, Grouzmann E, Brakch N, Svab J, Hovanessian AG, Latgé JP. Dipeptidyl-peptidase IV secreted by Aspergillus fumigatus, a fungus pathogenic to humans. Infect Immun. 1997;65(8):3042–7.

    PubMed  CAS  Google Scholar 

  11. Shankar J, Nigam S, Saxena S, Madan T, Sarma PU. Identification and assignment of function to the genes of Aspergillus fumigatus expressed at 37°C. J Eukaryot Microbiol. 2004;51(4):428–32.

    Article  PubMed  CAS  Google Scholar 

  12. Shankar J, Madan T, Basir SF, Sarma PU. Identification and characterization of polyubiquitin gene from cDNA library of Aspergillus fumigatus. Indian J Clin Biochem. 2005;20(1):208–12.

    Article  CAS  Google Scholar 

  13. Gautam P, Madan T, Gade WN, Sarma PU. Immunoproteomic analysis of secretory proteins of Aspergillus fumigatus with specific Ig E immunoreactivity. Indian J Clin Biochem. 2006;21(2):12–9.

    Article  CAS  Google Scholar 

  14. Upadhyay SK, Mahajan L, Ramjee S, Singh Y, Basir SF, Madan T. Expressed sequence tags of Aspergillus fumigatus: extension of catalogue and their evaluation as putative drug targets and/or diagnostic markers. Indian J Clin Biochem. 2009;24(2):131–6.

    Article  CAS  Google Scholar 

  15. Sarma PU, Madan T, Priyadarsini P, Haq W, Katti SB. Polypetides useful for diagnosis of Aspergillus fumigatus and a process for preparing for the same. US patent 6262231.

  16. Sarma PU, Madan T, Priyadarsini P, Haq W, Katti SB. A process for the preparation of a novel synthetic peptide epitope useful for diagnosis of aspergillosis. Indian patent 184440.

  17. Sarma PU, Madan T, Saxena S. Method of detection of SP-A2 gene variants useful for prediction of predisposition to aspergillosis. US patent 7288376.

  18. http://www.allergen.org/search.php?allergensource=Aspergillus+fumigatus.

  19. Gautam P, Sundaram CS, Madan T, Gade WN, Shah A, Sirdeshmukh R, Sarma PU. Identification of novel allergens of Aspergillus fumigatus using immunoproteomics approach. Clin Exp Allergy. 2007;37(8):1239–49.

    Article  PubMed  CAS  Google Scholar 

  20. Sarma PV, Purkayastha S, Madan T, Sarma PU. Expression of an epitopic region of AspfI, an allergen/antigen/cytotoxin of Aspergillus fumigatus. Immunol Lett. 1999;70(3):151–5.

    Article  PubMed  CAS  Google Scholar 

  21. Madan T, Arora N, Sarma PU. Ribonuclease activity dependent cytotoxicity of Asp fl, a major allergen of A. fumigatus. Mol Cell Biochem. 1997;175(1–2):21–7.

    Article  PubMed  CAS  Google Scholar 

  22. Saxena S, Madan T, Muralidhar K, Sarma PU. cDNA cloning, expression and characterization of an allergenic L3 ribosomal protein of Aspergillus fumigatus. Clin Exp Immunol. 2003;134(1):86–91.

    Article  PubMed  CAS  Google Scholar 

  23. Nigam S, Sarma PV, Ghosh PC, Sarma PU. Characterization of Aspergillus fumigatus protein disulfide isomerase family gene. Gene. 2001;281(1–2):143–50.

    Article  PubMed  CAS  Google Scholar 

  24. Madan T, Banerjee B, Bhatnagar PK, Shah A, Sarma PU. Identification of 45 kD antigen in immune complexes of patients of allergic bronchopulmonary aspergillosis. Mol Cell Biochem. 1997;166(1–2):111–6.

    Article  PubMed  CAS  Google Scholar 

  25. Hedayati MT, Pasqualotto AC, Warn PA, Bowyer P, Denning DW. Aspergillus flavus: human pathogen, allergen and mycotoxin producer. Microbiology. 2007;153(Pt 6):1677–92.

    Article  PubMed  CAS  Google Scholar 

  26. St Leger RJ, Screen SE, Shams-Pirzadeh B. Lack of host specialization in Aspergillus flavus. Appl Environ Microbiol. 2000;66(1):320–4.

    Article  PubMed  CAS  Google Scholar 

  27. Mellon JE, Cotty PJ, Dowd MK. Aspergillus flavus hydrolases: their roles in pathogenesis and substrate utilization. Appl Microbiol Biotechnol. 2007;77(3):497–504.

    Article  PubMed  CAS  Google Scholar 

  28. Madan T, Kishore U, Shah A, Eggleton P, Strong P, Wang JY, Aggrawal SS, Sarma PU, Reid KB. Lung surfactant proteins A and D can inhibit specific IgE binding to the allergens of Aspergillus fumigatus and block allergen-induced histamine release from human basophils. Clin Exp Immunol. 1997;110(2):241–9.

    Article  PubMed  CAS  Google Scholar 

  29. Madan T, Eggleton P, Kishore U, Strong P, Aggrawal SS, Sarma PU, Reid KB. Binding of pulmonary surfactant proteins A and D to Aspergillus fumigatus conidia enhances phagocytosis and killing by human neutrophils and alveolar macrophages. Infect Immun. 1997;65(8):3171–9.

    PubMed  CAS  Google Scholar 

  30. Madan T, Kishore U, Singh M, Strong P, Clark H, Hussain EM, Reid KB, Sarma PU. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Clin Invest. 2001;107(4):467–75.

    Article  PubMed  CAS  Google Scholar 

  31. Madan T, Kishore U, Singh M, Strong P, Clark H, Hussain EM, Reid KB, Sarma PU. Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens. J Immunol. 2005;174(11):6943–54.

    PubMed  CAS  Google Scholar 

  32. Madan T, Reid KB, Clark H, Singh M, Nayak A, Sarma PU, Hawgood S, Kishore U. Susceptibility of mice genetically deficient in SP-A or SP-D gene to invasive pulmonary aspergillosis. Mol Immunol. 2010;47(10):1923–30.

    Article  PubMed  CAS  Google Scholar 

  33. Kaur S, Gupta VK, Thiel S, Sarma PU, Madan T. Protective role of mannan-binding lectin in a murine model of invasive pulmonary aspergillosis. Clin Exp Immunol. 2007;148(2):382–9.

    Article  PubMed  CAS  Google Scholar 

  34. Madan T, Kaur S, Saxena S, Singh M, Kishore U, Thiel S, Reid KB, Sarma PU. Role of collectins in innate immunity against aspergillosis. Med Mycol. 2005;43(Suppl 1):S155–63.

    Article  PubMed  CAS  Google Scholar 

  35. Madan T, Kaur S, Saxena S, Singh M, Kishore U, Thiel S, Reid KB, Sarma PU. Role of collectins in innate immunity against aspergillosis. Immunobiology. 2002;205(4–5):610–8. Review.

    PubMed  Google Scholar 

  36. Singh M, Madan T, Waters P, Sonar S, Singh SK, Kamran MF, Bernal AL, Sarma PU, Singh VK, Crouch EC, Kishore U. Therapeutic effects of recombinant forms of full-length and truncated human surfactant protein D in a murine model of invasive pulmonary aspergillosis. Mol Immunol. 2009;46(11–12):2363–9.

    Article  PubMed  CAS  Google Scholar 

  37. Mahajan L, Madan T, Kamal N, Singh VK, Sim RB, Telang SD, Ramchand CN, Waters P, Kishore U, Sarma PU. Recombinant surfactant protein-D selectively increase apoptosis in eosinophils of allergic asthmatics and enhances uptake of apoptotic eosinophils by macrophages. Int Immunol. 2008;20(8):993–1007.

    Article  PubMed  CAS  Google Scholar 

  38. Vaid M, Kaur S, Sambatakou H, Madan T, Denning DW, Sarma PU. Distinct alleles of mannose-binding lectin (MBL) and surfactant proteins A (SP-A) in patients with chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Clin Chem Lab Med. 2007;45(2):183–6.

    Article  PubMed  CAS  Google Scholar 

  39. Upadhyay SK, Mahajan L, Ramjee S, Singh Y, Basir SF, Madan T. Identification and characterization of a laminin-binding protein of Aspergillus fumigatus: extracellular thaumatin domain protein (AfCalAp). J Med Microbiol. 2009;58(Pt 6):714–22.

    Article  PubMed  CAS  Google Scholar 

  40. Abad A, Victoria Fernández-Molina J, Bikandi J, Ramírez A, Margareto J, Sendino J, Luis Hernando F, Pontón J, Garaizar J, Rementeria A. What makes Aspergillus fumigatus a successful pathogen? Genes and molecules involved in invasive aspergillosis. Rev Iberoam Micol. 2010;27(4):155–82.

    Article  PubMed  Google Scholar 

  41. Rementeria A, López-Molina N, Ludwig A, Vivanco AB, Bikandi J, Pontón J, Garaizar J. Genes and molecules involved in Aspergillus fumigatus virulence. Rev Iberoam Micol. 2005;22(1):1–23.

    Article  PubMed  Google Scholar 

  42. Pihet M, Vandeputte P, Tronchin G, Renier G, Saulnier P, Georgeault S, Mallet R, Chabasse D, Symoens F, Bouchara JP. Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia. BMC Microbiol. 2009;9:177.

    Article  PubMed  CAS  Google Scholar 

  43. Yu JH, Mah JH, Seo JA. Growth and developmental control in the model and pathogenic aspergilli. Eukaryot Cell. 2006;5(10):1577–84.

    Article  PubMed  CAS  Google Scholar 

  44. Hu W, Sillaots S, Lemieux S, Davison J, Kauffman S, Breton A, Linteau A, Xin C, Bowman J, Becker J, Jiang B, Roemer T. Essential gene identification and drug target prioritization in Aspergillus fumigatus. PLoS Pathog. 2007;3(3):e24.

    Article  PubMed  CAS  Google Scholar 

  45. Beauvais A, Latgé JP. Membrane and cell wall targets in Aspergillus fumigatus. Drug Resist Updat. 2001;4(1):38–49.

    Article  PubMed  CAS  Google Scholar 

  46. Chamilos G, Kontoyiannis DP. Update on antifungal drug resistance mechanisms of Aspergillus fumigatus. Drug Resist Updat. 2005;8(6):344–58.

    Article  PubMed  CAS  Google Scholar 

  47. Latge JP, Mouyna I, Tekaia F, Beauvais A, Debeaupuis JP, Nierman W. Specific molecular features in the organization and biosynthesis of the cell wall of Aspergillus fumigatus. Med Mycol. 2005;43:S15–22.

    Article  PubMed  CAS  Google Scholar 

  48. Ibrahim-Granet O, Dubourdeau M, Latgé JP, Ave P, Huerre M, Brakhage AA, Brock M. Methylcitrate synthase from Aspergillus fumigatus is essential for manifestation of invasive aspergillosis. Cell Microbiol. 2008;10(1):134–48.

    PubMed  CAS  Google Scholar 

  49. Maerker C, Rohde M, Brakhage AA, Brock M. Methylcitrate synthase from Aspergillus fumigatus. Propionyl-CoA affects polyketide synthesis, growth and morphology of conidia. FEBS J. 2005;272(14):3615–30.

    Article  PubMed  CAS  Google Scholar 

  50. Lorenz MC, Fink GR. The glyoxylate cycle is required for fungal virulence. Nature. 2001;412(6842):83–6.

    Article  PubMed  CAS  Google Scholar 

  51. Olivas I, Royuela M, Romero B, Monteiro MC, Mínguez JM, Laborda F, De Lucas JR. Ability to grow on lipids accounts for the fully virulent phenotype in neutropenic mice of Aspergillus fumigatus null mutants in the key glyoxylate cycle enzymes. Fungal Genet Biol. 2008;45(1):45–60.

    Article  PubMed  CAS  Google Scholar 

  52. Schöbel F, Ibrahim-Granet O, Avé P, Latgé JP, Brakhage AA, Brock M. Aspergillus fumigatus does not require fatty acid metabolism via isocitrate lyase for development of invasive aspergillosis. Infect Immun. 2007;75(3):1237–44.

    Article  PubMed  CAS  Google Scholar 

  53. Thevelein JM. Regulation of trehalose mobilization in fungi. Microbiol Rev. 1984;48:42–59.

    PubMed  CAS  Google Scholar 

  54. Singer MA, Lindquist S. Multiple effects of trehalose on protein folding in vitro and in vivo. Mol Cell. 1998;1:639–48.

    Article  PubMed  CAS  Google Scholar 

  55. Al-Bader N, Vanier G, Liu H, Gravelat FN, Urb M, Hoareau CM, Campoli P, Chabot J, Filler SG, Sheppard DC. Role of trehalose biosynthesis in Aspergillus fumigatus development, stress response, and virulence. Infect Immun. 2010;78(7):3007–18.

    Article  PubMed  CAS  Google Scholar 

  56. Puttikamonkul S, Willger SD, Grahl N, Perfect JR, Movahed N, Bothner B, Park S, Paderu P, Perlin DS, Cramer RA Jr. Trehalose 6-phosphate phosphatase is required for cell wall integrity and fungal virulence but not trehalose biosynthesis in the human fungal pathogen Aspergillus fumigatus. Mol Microbiol. 2010 Jun 9.

  57. Schöbel F, Jacobsen ID, Brock M. Evaluation of lysine biosynthesis as an antifungal drug target: biochemical characterization of Aspergillus fumigatus homocitrate synthase and virulence studies. Eukaryot Cell. 2010;9(6):878–93.

    Article  PubMed  CAS  Google Scholar 

  58. Abadio AK, Kioshima ES, Teixeira MM, Martins NF, Maigret B, Felipe MS. Comparative genomics allowed the identification of drug targets against human fungal pathogens. BMC Genomics. 2011;12(1):75.

    Article  PubMed  CAS  Google Scholar 

  59. Goffeau A. Genomics: multiple moulds. Nature. 2005;438(7071):1092–3.

    Article  PubMed  CAS  Google Scholar 

  60. Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Barrell B, Denning DW. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature. 2005;438(7071):1151–6.

    Article  PubMed  CAS  Google Scholar 

  61. Rokas A, Payne G, Fedorova ND, Baker SE, Machida M, Yu J, Georgianna DR, Dean RA, Bhatnagar D, Cleveland TE, Wortman JR, Maiti R, Joardar V, Amedeo P, Denning DW, Nierman WC. What can comparative genomics tell us about species concepts in the genus Aspergillus? Stud Mycol. 2007;59:11–7.

    Article  PubMed  CAS  Google Scholar 

  62. Scazzocchio C. Aspergillus genomes: secret sex and the secrets of sex. Trends Genet. 2006;22(10):521–5.

    Article  PubMed  CAS  Google Scholar 

  63. Brakhage AA, Schroeckh V. Fungal secondary metabolites—strategies to activate silent gene clusters. Fungal Genet Biol. 2011;48(1):15–22.

    Article  PubMed  CAS  Google Scholar 

  64. Khaldi N, Seifuddin FT, Turner G, Haft D, Nierman WC, Wolfe KH, Fedorova ND. SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol. 2010;47(9):736–41.

    Article  PubMed  CAS  Google Scholar 

  65. Gardiner DM, Howlett BJ. Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus. FEMS Microbiol Lett. 2005;248(2):241–8.

    Article  PubMed  CAS  Google Scholar 

  66. Coyle CM, Kenaley SC, Rittenour WR, Panaccione DG. Association of ergot alkaloids with conidiation in Aspergillus fumigatus. Mycologia. 2007;99(6):804–11.

    Article  PubMed  CAS  Google Scholar 

  67. Maiya S, Grundmann A, Li SM, Turner G. The fumitremorgin gene cluster of Aspergillus fumigatus: identification of a gene encoding brevianamide F synthetase. Chembiochem. 2006;7(7):1062–9.

    Article  PubMed  CAS  Google Scholar 

  68. Hissen AH, Wan AN, Warwas ML, Pinto LJ, Moore MM. The Aspergillus fumigatus siderophore biosynthetic gene sidA, encoding l-ornithine N5-oxygenase, is required for virulence. Infect Immun. 2005;73(9):5493–503.

    Article  PubMed  CAS  Google Scholar 

  69. Lewis RE, Wiederhold NP, Chi J, Han XY, Komanduri KV, Kontoyiannis DP, Prince RA. Detection of gliotoxin in experimental and human aspergillosis. Infect Immun. 2005;73(1):635–7.

    Article  PubMed  CAS  Google Scholar 

  70. Frisvad JC, Rank C, Nielsen KF, Larsen TO. Metabolomics of Aspergillus fumigatus. Med Mycol. 2009;47(s1):S53–71.

    Article  PubMed  CAS  Google Scholar 

  71. Pel HJ, Visser J, Stam H. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat Biotechnol. 2007;25(2):221–31.

    Article  PubMed  Google Scholar 

  72. Vala AK, Dave BP, Dube HC. Chemical characterization and quantification of siderophores produced by marine and terrestrial aspergilli. Can J Microbiol. 2006;52(6):603–7.

    Article  PubMed  CAS  Google Scholar 

  73. Mogensen JM, Nielsen KF, Samson RA, Frisvad JC, Thrane U. Effect of temperature and water activity on the production of fumonisins by Aspergillus niger and different Fusarium species. BMC Microbiol. 2009;9:281.

    Article  PubMed  CAS  Google Scholar 

  74. Chang PK, Horn BW, Dorner JW. Clustered genes involved in cyclopiazonic acid production are next to the aflatoxin biosynthesis gene cluster in Aspergillus flavus. Fungal Genet Biol. 2009;46(2):176–82.

    Article  PubMed  CAS  Google Scholar 

  75. Juvvadi PR, Seshime Y, Kitamoto K. Genomics reveals traces of fungal phenylpropanoid-flavonoid metabolic pathway in the filamentous fungus Aspergillus oryzae. J Microbiol. 2005;43(6):475–86.

    PubMed  CAS  Google Scholar 

  76. Kiyota T, Hamada R, Sakamoto K, Iwashita K, Yamada O, Mikami S. Aflatoxin non-productivity of Aspergillus oryzae caused by loss of function in the aflJ gene product. J Biosci Bioeng. 2011;111(5):512–517.

    Google Scholar 

  77. Calvo AM, Wilson RA, Bok JW, Keller NP. Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev. 2002;66(3):447–59.

    Article  PubMed  CAS  Google Scholar 

  78. Chiang YM, Chang SL, Oakley BR, Wang CC. Recent advances in awakening silent biosynthetic gene clusters and linking orphan clusters to natural products in microorganisms. Curr Opin Chem Biol. 2011;15(1):137–43.

    Article  PubMed  CAS  Google Scholar 

  79. Bok JW, Keller NP. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot Cell. 2004;3(2):527–35.

    Article  PubMed  CAS  Google Scholar 

  80. Bok JW, Balajee SA, Marr KA, Andes D, Nielsen KF, Frisvad JC, Keller NP. LaeA, a regulator of morphogenetic fungal virulence factors. Eukaryot Cell. 2005;4(9):1574–82.

    Article  PubMed  CAS  Google Scholar 

  81. Kale SP, Milde L, Trapp MK, Frisvad JC, Keller NP, Bok JW. Requirement of LaeA for secondary metabolism and sclerotial production in Aspergillus flavus. Fungal Genet Biol. 2008;45(10):1422–9.

    Article  PubMed  CAS  Google Scholar 

  82. Bentley R, Bennet JW. Construction polyketides: from collie to combinatorial biosynthesis. Annu Rev Microbiol. 1999;53:411–46.

    Article  PubMed  CAS  Google Scholar 

  83. Chiang YM, Szewczyk E, Davidson AD, Keller N, Oakley BR, Wang CC. A gene cluster containing two fungal polyketide synthases encodes the biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus nidulans. J Am Chem Soc. 2009;131(8):2965–70.

    Article  PubMed  CAS  Google Scholar 

  84. Reyes-Dominguez Y, Bok JW, Berger H, Shwab EK, Basheer A, Gallmetzer A, Scazzocchio C, Keller N, Strauss J. Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans. Mol Microbiol. 2010;76(6):1376–86.

    Article  PubMed  CAS  Google Scholar 

  85. http://www.knowmycotoxins.com/regulations.htm.

  86. Zhang W, Tang Y. In vitro analysis of type II polyketide synthase. Methods Enzymol. 2009;459:367–93.

    Article  PubMed  CAS  Google Scholar 

  87. Abe I, Morita H. Structure and function of the chalcone synthase superfamily of plant type III polyketide synthases. Nat Prod Rep. 2010;27(6):809–38.

    Article  PubMed  CAS  Google Scholar 

  88. Manzoni M, Rollini M. Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs. Appl Microbiol Biotechnol. 2002;58(5):555–64.

    Article  PubMed  CAS  Google Scholar 

  89. Tang Y, Chen AY, Kim CY, Cane DE, Khosla C. Structural and mechanistic analysis of protein interactions in module 3 of the 6-deoxyerythronolide B synthase. Chem Biol. 2007;14(8):931–43.

    Article  PubMed  CAS  Google Scholar 

  90. Seshime Y, Juvvadi PR, Fuji I, Kitamoto K. Discovery of a novel superfamily of type III polyketide synthases in Aspergillus oryzae. Biochem Biophys Res Commun. 2005;331(1):253–60.

    Google Scholar 

  91. Cleveland TE, Yu J, Fedorova N, Bhatnagar D, Payne GA, Nierman WC, Bennett JW. Potential of Aspergillus flavus genomics for applications in biotechnology. Trends Biotechnol. 2009;27(3):151–7. Review.

    Article  PubMed  CAS  Google Scholar 

  92. Chiang YM, Oakley BR, Keller NP, Wang CC. Unraveling polyketide synthesis in members of the genus Aspergillus. Appl Microbiol Biotechnol. 2010;86(6):1719–36.

    Article  PubMed  CAS  Google Scholar 

  93. Crawford JM, Thomas PM, Scheerer JR, Vagstad AL, Kelleher NL, Townsend CA. Deconstruction of iterative multidomain polyketide synthase function. Science. 2008;320:243–6.

    Article  PubMed  CAS  Google Scholar 

  94. Langfelder K, Jahn B, Gehringer H, Schmidt A, Wanner G, Brakhage AA. Identification of a polyketide synthase gene (pksP) of Aspergillus fumigatus involved in conidial pigment biosynthesis and virulence. Med Microbiol Immunol. 1998;187:79–89.

    Article  PubMed  CAS  Google Scholar 

  95. Watanabe A, Fujii I, Tsai HF, Chang YC, Kwon-Chung KJ, Ebizuka Y. Aspergillus fumigatus alb1 encodes naphthopyrone synthase when expressed in Aspergillus oryzae. FEMS Microbiol Lett. 2000;192:39–44.

    Article  PubMed  CAS  Google Scholar 

  96. Jahn B, Langfelder K, Schneider U, Schindel C, Brakhage AA. PKSP-dependent reduction of phagolysosome fusion and intracellular kill of Aspergillus fumigatus conidia by human monocyte-derived macrophages. Cell Microbiol. 2002;4:793–803.

    Article  PubMed  CAS  Google Scholar 

  97. Langfelder K, Philippe B, Jahn B, Latgé JP, Brakhage AA. Differential expression of the Aspergillus fumigatus pksP gene detected in vitro and in vivo with green fluorescent protein. Infect Immun. 2001;69:6411–8.

    Article  PubMed  CAS  Google Scholar 

  98. Pihet M, Vandeputte P, Tronchin G, Renier G, Saulnier P, Georgeault S, Mallet R, Chabasse D, Symoens F, Bouchara JP. Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia. BMC Microbiol. 2009;9:177.

    Article  PubMed  CAS  Google Scholar 

  99. Schmaler-Ripcke J, Sugareva V, Gebhardt P, Winkler R, Kniemeyer O, Heinekamp T, Brakhage AA. Production of pyomelanin, a second type of melanin, via the tyrosine degradation pathway in Aspergillus fumigatus. Appl Environ Microbiol. 2009;75:493–503.

    Article  PubMed  CAS  Google Scholar 

  100. Jørgensen TR, Park J, Arentshorst M, van Welzen AM, Lamers G, Vankuyk PA, Damveld RA, van den Hondel CA, Nielsen KF, Frisvad JC, Ram AF. The molecular and genetic basis of conidial pigmentation in Aspergillus niger. Fungal Genet Biol. 2011;48(5):544–53.

    Article  PubMed  CAS  Google Scholar 

  101. Jahn B, Boukhallouk F, Lotz J, Langfelder K, Wanner G, Brakhage AA. Interaction of human phagocytes with pigmentless Aspergillus conidia. Infect Immun. 2000;68(6):3736–9.

    Article  PubMed  CAS  Google Scholar 

  102. Agarwal R, Singh N, Aggarwal AN. An unusual association between Mycobacterium tuberculosis and Aspergillus fumigatus. Monaldi Arch Chest Dis. 2008;69(1):32–4.

    PubMed  CAS  Google Scholar 

  103. Sankaranarayanan R, Saxena P, Marathe UB, Gokhale RS, Shanmugam VM, Rukmini R. A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites. Nat Struct Mol Biol. 2004;11(9):894–900.

    Article  PubMed  CAS  Google Scholar 

  104. Chopra T, Gokhale RS. Polyketide versatility in the biosynthesis of complex mycobacterial cell wall lipids. Methods Enzymol. 2009;459:259–94.

    Article  PubMed  CAS  Google Scholar 

  105. Payne GA, Brown MP. Genetics and physiology of aflatoxin biosynthesis. Annu Rev Phytopathol. 1998;36:329–62.

    Article  PubMed  CAS  Google Scholar 

  106. Yu JJ, Chang PK, Ehrlich KC, et al. Clustered pathway genes in aflatoxin biosynthesis. Appl Environ Microbiol. 2004;70:1253–62.

    Article  PubMed  CAS  Google Scholar 

  107. Yabe K, Nakajima H. Enzyme reactions and genes in aflatoxin biosynthesis. Appl Microbiol Biotechnol. 2004;64(6):745–55. Review.

    Article  PubMed  CAS  Google Scholar 

  108. Yu JH, Leonard TJ. Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I polyketide synthase. J Bacteriol. 1995;177(16):4792–800.

    PubMed  CAS  Google Scholar 

  109. Nicholson MJ, Koulman A, Monahan BJ, Pritchard BL, Payne GA, Scott B. Identification of two aflatrem biosynthesis gene loci in Aspergillus flavus and metabolic engineering of Penicillium paxilli to elucidate their function. Appl Environ Microbiol. 2009;75(23):7469–81.

    Article  PubMed  CAS  Google Scholar 

  110. Georgianna DR, Fedorova ND, Burroughs JL, Dolezal AL, Bok JW, Horowitz-Brown S, Woloshuk CP, Yu J, Keller NP, Payne GA. Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters. Mol Plant Pathol. 2010;11(2):213–26.

    Article  PubMed  CAS  Google Scholar 

  111. Ma SM, Li JW, Choi JW, Zhou H, Lee KK, Moorthie VA, Xie X, Kealey JT, Da Silva NA, Vederas JC, Tang Y. Complete reconstitution of a highly reducing iterative polyketide synthase. Science. 2009;326(5952):589–92.

    Article  PubMed  CAS  Google Scholar 

  112. Hutchinson CR, Kennedy J, Park C, Kendrew S, Auclair K, Vederas J. Aspects of the biosynthesis of non-aromatic fungal polyketides by iterative polyketide synthases. Antonie Van Leeuwenhoek. 2000;78(3–4):287–95. Review.

    Article  PubMed  CAS  Google Scholar 

  113. Kennedy J, Auclair K, Kendrew SG, Park C, Vederas JC, Hutchinson CR. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science. 1999;284(5418):1368–72.

    Article  PubMed  CAS  Google Scholar 

  114. Ma SM, Tang Y. Biochemical characterization of the minimal polyketide synthase domains in the lovastatin nonaketide synthase LovB. FEBS J. 2007;274(11):2854–64.

    Article  PubMed  CAS  Google Scholar 

  115. Keller NP, Turner G, Bennett JW. Fungal secondary metabolism—from biochemistry to genomics. Nat Rev Microbiol. 2005;3:937–47.

    Article  PubMed  CAS  Google Scholar 

  116. Panagiotou G, Andersen MR, Grotkjaer T, Regueira TB, Nielsen J, Olsson L. Studies of the production of fungal polyketides in Aspergillus nidulans by using systems biology tools. Appl Environ Microbiol. 2009;75(7):2212–20.

    Article  PubMed  CAS  Google Scholar 

  117. Do JH, Miyano S. The GC and window-averaged DNA curvature profile of secondary metabolite gene cluster in Aspergillus fumigatus genome. Appl Microbiol Biotechnol. 2008;80(5):841–7.

    Article  PubMed  CAS  Google Scholar 

  118. Kroken S, Glass NL, Taylor JW, Yoder OC, Turgeon BG. Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Natl Acad Sci USA. 2003;100(26):15670–5.

    Article  PubMed  CAS  Google Scholar 

  119. Racil Z, Kocmanova I, Lengerova M, Weinbergerova B, Buresova L, Toskova M, Winterova J, Timilsina S, Rodriguez I, Mayer J. Difficulties in using 1, 3-{beta}-D-glucan as the screening test for the early diagnosis of invasive fungal infections in patients with haematological malignancies–high frequency of false-positive results and their analysis. J Med Microbiol. 2010;59(Pt 9):1016–22.

    Article  PubMed  CAS  Google Scholar 

  120. Atoui A, Mathieu F, Lebrihi A. Targeting a polyketide synthase gene for Aspergillus carbonarius quantification and ochratoxin A assessment in grapes using real-time PCR. Int J Food Microbiol. 2007;115(3):313–8.

    Article  PubMed  CAS  Google Scholar 

  121. Usha Sarma P. Fascinating Potential of Aspergilli. Indian J Clin Biochem. 2010;25(4):331–4.

    Article  Google Scholar 

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Acknowledgements

The facilities and the support provided at Division of Plant Pathology, Indian Agricultural Research Institute by Dr. R.K. Jain, Head of the Department and the Director, IARI are highly acknowledged.

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Correspondence to Sarma P. Usha.

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Bhetariya, P.J., Madan, T., Basir, S.F. et al. Allergens/Antigens, Toxins and Polyketides of Important Aspergillus Species. Ind J Clin Biochem 26, 104–119 (2011). https://doi.org/10.1007/s12291-011-0131-5

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