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Annual Review of Genetics

Volume 50, 2016

Regulation and Role of Fungal Secondary Metabolites

Abstract

Fungi have the capability to produce a tremendous number of so-called secondary metabolites, which possess a multitude of functions, e.g., communication signals during coexistence with other microorganisms, virulence factors during pathogenic interactions with plants and animals, and in medical applications. Therefore, research on this topic has intensified significantly during the past 10 years and thus knowledge of regulatory mechanisms and the understanding of the role of secondary metabolites have drastically increased. This review aims to depict the complexity of all the regulatory elements involved in controlling the expression of secondary metabolite gene clusters, ranging from epigenetic control and signal transduction pathways to global and specific transcriptional regulators. Furthermore, we give a short overview on the role of secondary metabolites, focusing on the interaction with other microorganisms in the environment as well as on pathogenic relationships.

Keyword(s): epigenetic regulation, interaction, secondary metabolism, signal transduction, transcriptional regulation, virulence factor
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/content/journals/10.1146/annurev-genet-120215-035203
2016-11-23
2024-04-20
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Literature Cited

  1. Abrudan MI, Smakman F, Grimbergen AJ, Westhoff S, Miller EL. 1.  et al. 2015. Socially mediated induction and suppression of antibiosis during bacterial coexistence. PNAS 112:11054–59 [Google Scholar]
  2. Albright JC, Henke MT, Soukup AA, McClure RA, Thomson RJ. 2.  et al. 2015. Large-scale metabolomics reveals a complex response of Aspergillus nidulans to epigenetic perturbation. ACS Chem. Biol. 10:1535–41 [Google Scholar]
  3. Albuquerque P, Casadevall A. 3.  2012. Quorum sensing in fungi—a review. Med. Mycol. 50:337–45 [Google Scholar]
  4. Altwasser R, Baldin C, Weber J, Guthke R, Kniemeyer O. 4.  et al. 2015. Network modeling reveals cross talk of MAP kinases during adaptation to caspofungin stress in Aspergillus fumigatus. PLOS ONE 10:e0136932 [Google Scholar]
  5. Alvi KA, Baker DD, Stienecker V, Hosken M, Nair BG. 5.  2000. Identification of inhibitors of inducible nitric oxide synthase from microbial extracts. J. Antibiot. 53:496–501 [Google Scholar]
  6. Atoui A, Bao D, Kaur N, Grayburn WS, Calvo AM. 6.  2008. Aspergillus nidulans natural product biosynthesis is regulated by MpkB, a putative pheromone response mitogen-activated protein kinase. Appl. Environ. Microbiol. 74:3596–600 [Google Scholar]
  7. Baldin C, Valiante V, Krüger T, Schafferer L, Haas H. 7.  et al. 2015. Comparative proteomics of a tor inducible Aspergillus fumigatus mutant reveals involvement of the Tor kinase in iron regulation. Proteomics 15:2230–43 [Google Scholar]
  8. Bayram Ö, Bayram ÖS, Ahmed YL, Maruyama J, Valerius O. 8.  et al. 2012. The Aspergillus nidulans MAPK module AnSte11-Ste50-Ste7-Fus3 controls development and secondary metabolism. PLOS Genet. 8:e1002816 [Google Scholar]
  9. Bayram Ö, Braus GH. 9.  2012. Coordination of secondary metabolism and development in fungi: the velvet family of regulatory proteins. FEMS Microbiol. Rev. 36:1–24 [Google Scholar]
  10. Bergmann S, Funk AN, Scherlach K, Schroeckh V, Shelest E. 10.  et al. 2010. Activation of a silent fungal polyketide biosynthesis pathway through regulatory cross talk with a cryptic nonribosomal peptide synthetase gene cluster. Appl. Environ. Microbiol. 76:8143–49 [Google Scholar]
  11. Bergmann S, Schümann J, Scherlach K, Lange C, Brakhage AA, Hertweck C. 11.  2007. Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat. Chem. Biol. 3:213–17 [Google Scholar]
  12. Berthier E, Lim FY, Deng Q, Guo CJ, Kontoyiannis DP. 12.  et al. 2013. Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites. PLOS Pathog. 9:e1003289 [Google Scholar]
  13. Bertuzzi M, Schrettl M, Alcazar-Fuoli L, Cairns TC, Munoz A. 13.  et al. 2014. The pH-responsive PacC transcription factor of Aspergillus fumigatus governs epithelial entry and tissue invasion during pulmonary aspergillosis. PLOS Pathog. 10:e1004413 [Google Scholar]
  14. Böhnert HU, Fudal I, Dioh W, Tharreau D, Notteghem JL, Lebrun MH. 14.  2004. A putative polyketide synthase/peptide synthetase from Magnaporthe grisea signals pathogen attack to resistant rice. Plant Cell 16:2499–513 [Google Scholar]
  15. Bok JW, Chiang YM, Szewczyk E, Reyes-Dominguez Y, Davidson AD. 15.  et al. 2009. Chromatin-level regulation of biosynthetic gene clusters. Nat. Chem. Biol. 5:462–64 [Google Scholar]
  16. Bok JW, Chung D, Balajee SA, Marr KA, Andes D. 16.  et al. 2006. GliZ, a transcriptional regulator of gliotoxin biosynthesis, contributes to Aspergillus fumigatus virulence. Infect. Immun. 74:6761–68 [Google Scholar]
  17. Bok JW, Keller NP. 17.  2004. LaeA, a regulator of secondary metabolism in Aspergillus spp. Eukaryot. Cell 3:527–35 [Google Scholar]
  18. Brakhage AA. 18.  1998. Molecular regulation of β-lactam biosynthesis in filamentous fungi. Microbiol. Mol. Biol. Rev. 62:547–85 [Google Scholar]
  19. Brakhage AA. 19.  2013. Regulation of fungal secondary metabolism. Nat. Rev. Microbiol. 11:21–32 [Google Scholar]
  20. Brakhage AA, Schroeckh V. 20.  2011. Fungal secondary metabolites: strategies to activate silent gene clusters. Fungal Genet. Biol. 48:15–22 [Google Scholar]
  21. Brakhage AA, Schuemann J, Bergmann S, Scherlach K, Schroeckh V, Hertweck C. 21.  2008. Activation of fungal silent gene clusters: a new avenue to drug discovery. Prog. Drug Res. Fortschr. Arzneimittelforschung Prog. Rech. Pharm. 66:13–12 [Google Scholar]
  22. Brown DW, Yu JH, Kelkar HS, Fernandes M, Nesbitt TC. 22.  et al. 1996. Twenty-five coregulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. PNAS 93:1418–22 [Google Scholar]
  23. Bruns S, Seidler M, Albrecht D, Salvenmoser S, Remme N. 23.  et al. 2010. Functional genomic profiling of Aspergillus fumigatus biofilm reveals enhanced production of the mycotoxin gliotoxin. Proteomics 10:3097–107 [Google Scholar]
  24. Burmester A, Shelest E, Glöckner G, Heddergott C, Schindler S. 24.  et al. 2011. Comparative and functional genomics provide insights into the pathogenicity of dermatophytic fungi. Genome Biol. 12:R7 [Google Scholar]
  25. Caddick MX, Arst HN Jr. 25.  1998. Deletion of the 389 N-terminal residues of the transcriptional activator AREA does not result in nitrogen metabolite derepression in Aspergillus nidulans. J. Bacteriol. 180:5762–64 [Google Scholar]
  26. Carlton WW, Stack ME, Eppley RM. 26.  1976. Hepatic alterations produced in mice by xanthomegnin and viomellein, metabolites of Penicillium viridicatum. Toxicol. Appl. Pharmacol. 38:455–59 [Google Scholar]
  27. Chang PK, Ehrlich KC. 27.  2013. Genome-wide analysis of the Zn(II)2Cys6 zinc cluster-encoding gene family in Aspergillus flavus. Appl. Microbiol. Biotechnol. 97:4289–300 [Google Scholar]
  28. Chang PK, Yu J, Bhatnagar D, Cleveland TE. 28.  2000. Characterization of the Aspergillus parasiticus major nitrogen regulatory gene, areA. Biochim. Biophys. Acta 1491:263–66 [Google Scholar]
  29. Chen XR, Hu QB, Yu XQ, Ren SX. 29.  2014. Effects of destruxins on free calcium and hydrogen ions in insect hemocytes. Insect Sci. 21:31–38 [Google Scholar]
  30. Chiang YM, Szewczyk E, Davidson AD, Keller N, Oakley BR, Wang CC. 30.  2009. A gene cluster containing two fungal polyketide synthases encodes the biosynthetic pathway for a polyketide, asperfuranone, in Aspergillus nidulans. J. Am. Chem. Soc. 131:2965–70 [Google Scholar]
  31. Chidananda C, Rao LJ, Sattur AP. 31.  2006. Sclerotiorin, from Penicillium frequentans, a potent inhibitor of aldose reductase. Biotechnol. Lett. 28:1633–36 [Google Scholar]
  32. Chung YM, El-Shazly M, Chuang DW, Hwang TL, Asai T. 32.  et al. 2013. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, induces the production of anti-inflammatory cyclodepsipeptides from Beauveria felina. J. Nat. Prod. 76:1260–66 [Google Scholar]
  33. Dalmais B, Schumacher J, Moraga J, Le Pêcheur P, Tudzynski B. 33.  et al. 2011. The Botrytis cinerea phytotoxin botcinic acid requires two polyketide synthases for production and has a redundant role in virulence with botrydial. Mol. Plant Pathol. 12:564–79 [Google Scholar]
  34. Daub ME, Herrero S, Chung KR. 34.  2013. Reactive oxygen species in plant pathogenesis: the role of perylenequinone photosensitizers. Antiox. Redox Signal. 19:970–89 [Google Scholar]
  35. Davies J. 35.  1990. What are antibiotics? Archaic functions for modern activities. Mol. Microbiol. 4:1227–32 [Google Scholar]
  36. De Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G, Posas F. 36.  2004. The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427:370–74 [Google Scholar]
  37. de Weert S, Kuiper I, Lagendijk EL, Lamers GE, Lugtenberg BJ. 37.  2004. Role of chemotaxis toward fusaric acid in colonization of hyphae of Fusarium oxysporum f. sp. radicis-lycopersici by Pseudomonas fluorescens WCS365. Mol. Plant-Microbe Interact. 17:1185–91 [Google Scholar]
  38. Dowzer CE, Kelly JM. 38.  1991. Analysis of the creA gene, a regulator of carbon catabolite repression in Aspergillus nidulans. Mol. Cell. Biol. 11:5701–9 [Google Scholar]
  39. Flaherty JE, Payne GA. 39.  1997. Overexpression of aflR leads to upregulation of pathway gene transcription and increased aflatoxin production in Aspergillus flavus. Appl. Environ. Microbiol. 63:3995–4000 [Google Scholar]
  40. Flaherty JE, Pirttila AM, Bluhm BH, Woloshuk CP. 40.  2003. PAC1, a pH-regulatory gene from Fusarium verticillioides. Appl. Environ. Microbiol. 69:5222–27 [Google Scholar]
  41. Fleming A. 41.  1929. On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ. Br. J. Exp. Pathol. 10:226–36 [Google Scholar]
  42. Fox EM, Howlett BJ. 42.  2008. Secondary metabolism: regulation and role in fungal biology. Curr. Opin. Microbiol. 11:481–87 [Google Scholar]
  43. Frey-Klett P, Burlinson P, Deveau A, Barret M, Tarkka M, Sarniguet A. 43.  2011. Bacterial-fungal interactions: hyphens between agricultural, clinical, environmental, and food microbiologists. Microbiol. Mol. Biol. Rev. 75:583–609 [Google Scholar]
  44. Gacek A, Strauss J. 44.  2012. The chromatin code of fungal secondary metabolite gene clusters. Appl. Microbiol. Biotechnol. 95:1389–404 [Google Scholar]
  45. García-Martinez J, Adám AL, Avalos J. 45.  2012. Adenylyl cyclase plays a regulatory role in development, stress resistance and secondary metabolism in Fusarium fujikuroi. PLOS ONE 7:e28849 [Google Scholar]
  46. García-Rico RO, Fierro F, Mauriz E, Gómez A. 46.  Fernández-Bodega MÁ, Martín JF. 2008. The heterotrimeric Ga protein Pga1 regulates biosynthesis of penicillin, chrysogenin and roquefortine in Penicillium chrysogenum. Microbiology 154:3567–78 [Google Scholar]
  47. Gauthier GM, Keller NP. 47.  2013. Crossover fungal pathogens: the biology and pathogenesis of fungi capable of crossing kingdoms to infect plants and humans. Fungal Genet. Biol. 61:146–57 [Google Scholar]
  48. Gibbons JG, Beauvais A, Beau R, McGary KL, Latge JP, Rokas A. 48.  2012. Global transcriptome changes underlying colony growth in the opportunistic human pathogen Aspergillus fumigatus. Eukaryot. Cell 11:68–78 [Google Scholar]
  49. Giuliano Garisto Donzelli B, Gibson DM, Krasnoff SB. 49.  2015. Intracellular siderophore but not extracellular siderophore is required for full virulence in Metarhizium robertsii. Fungal Genet. Biol. 82:56–68 [Google Scholar]
  50. Giuliano Garisto Donzelli B, Krasnoff SB, Moon YS, Churchill AC, Gibson DM. 50.  2012. Genetic basis of destruxin production in the entomopathogen Metarhizium robertsii. Curr. Genet. 58:105–16 [Google Scholar]
  51. Grandclément C, Tannières M, Moréra S, Dessaux Y, Faure D. 51.  2016. Quorum quenching: role in nature and applied developments. FEMS Microbiol. Rev. 40:86–116 [Google Scholar]
  52. Grosse C, Heinekamp T, Kniemeyer O, Gehrke A, Brakhage AA. 52.  2008. Protein kinase A regulates growth, sporulation, and pigment formation in Aspergillus fumigatus. Appl. Environ. Microbiol. 74:4923–33 [Google Scholar]
  53. Gsaller F, Hortschansky P, Beattie SR, Klammer V, Tuppatsch K. 53.  et al. 2014. The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess. EMBO J. 33:2261–76 [Google Scholar]
  54. Gupta AK, Ahmad I, Borst I, Summerbell RC. 54.  2000. Detection of xanthomegnin in epidermal materials infected with Trichophyton rubrum. J. Investig. Dermatol. 115:901–5 [Google Scholar]
  55. Gutjahr C, Parniske M. 55.  2013. Cell and developmental biology of arbuscular mycorrhiza symbiosis. Annu. Rev. Cell Dev. Biol. 29:593–617 [Google Scholar]
  56. Haas H, Eisendle M, Turgeon BG. 56.  2008. Siderophores in fungal physiology and virulence. Annu. Rev. Phytopathol. 46:149–87 [Google Scholar]
  57. Heinekamp T, Thywissen A, Macheleidt J, Keller S, Valiante V, Brakhage AA. 57.  2013. Aspergillus fumigatus melanins: interference with the host endocytosis pathway and impact on virulence. Front. Microbiol. 3:440 [Google Scholar]
  58. Herrmann M, Spröte P, Brakhage AA. 58.  2006. Protein kinase C (PkcA) of Aspergillus nidulans is involved in penicillin production. Appl. Environ. Microbiol. 72:2957–70 [Google Scholar]
  59. Homer CM, Summers DK, Goranov Al, Clark SC, Wiesner DL. 59.  et al. 2016. Intracellular action of a secreted peptide requried for fungal virulence. Cell Host Microbe. 19:849–64 [Google Scholar]
  60. Hong SY, Roze LV, Linz JE. 60.  2013. Oxidative stress–related transcription factors in the regulation of secondary metabolism. Toxins 5:683–702 [Google Scholar]
  61. Hortschansky P, Eisendle M, Al-Abdallah Q, Schmidt AD, Bergmann S. 61.  et al. 2007. Interaction of HapX with the CCAAT-binding complex: a novel mechanism of gene regulation by iron. EMBO J. 26:3157–68 [Google Scholar]
  62. Howard RJ, Valent B. 62.  1996. Breaking and entering: host penetration by the fungal rice blast pathogen Magnaporthe grisea. Annu. Rev. Microbiol. 50:491–512 [Google Scholar]
  63. Hunt VL, Charnley AK. 63.  2011. The inhibitory effect of the fungal toxin, destruxin A, on behavioural fever in the desert locust. J. Insect Physiol. 57:1341–46 [Google Scholar]
  64. Irmer H, Tarazona S, Sasse C, Olbermann P, Loeffler J. 64.  et al. 2015. RNAseq analysis of Aspergillus fumigatus in blood reveals a just wait and see resting stage behavior. BMC Genom. 16:640 [Google Scholar]
  65. Jain R, Valiante V, Remme N, Docimo T, Heinekamp T. 65.  et al. 2011. The MAP kinase MpkA controls cell wall integrity, oxidative stress response, gliotoxin production and iron adaptation in Aspergillus fumigatus. Mol. Microbiol. 82:39–53 [Google Scholar]
  66. Janus D, Hortschansky P, Kück U. 66.  2008. Identification of a minimal cre1 promoter sequence promoting glucose-dependent gene expression in the β-lactam producer Acremonium chrysogenum. Curr. Genet. 53:35–48 [Google Scholar]
  67. Jekosch K, Kück U. 67.  2000. Loss of glucose repression in an Acremonium chrysogenum β-lactam producer strain and its restoration by multiple copies of the cre1 gene. Appl. Microbiol. Biotechnol. 54:556–63 [Google Scholar]
  68. Jirakkakul J, Cheevadhanarak S, Punya J, Chutrakul C, Senachak J. 68.  et al. 2015. Tenellin acts as an iron chelator to prevent iron-generated reactive oxygen species toxicity in the entomopathogenic fungus Beauveria bassiana. FEMS Microbiol. Lett. 362:1–8 [Google Scholar]
  69. Karimi-Aghcheh R, Bok JW, Phatale PA, Smith KM, Baker SE. 69.  et al. 2013. Functional analyses of Trichoderma reesei LAE1 reveal conserved and contrasting roles of this regulator. G3 3:369–78 [Google Scholar]
  70. Kazan K, Gardiner DM, Manners JM. 70.  2012. On the trail of a cereal killer: recent advances in Fusarium graminearum pathogenomics and host resistance. Mol. Plant Pathol. 13:399–413 [Google Scholar]
  71. Keller NP, Nesbitt C, Sarr B, Phillips TD, Burow GB. 71.  1997. pH Regulation of sterigmatocystin and aflatoxin biosynthesis in Aspergillus spp. Phytopathology 87:643–48 [Google Scholar]
  72. Kennedy J, Auclair K, Kendrew SG, Park C, Vederas JC, Hutchinson CR. 72.  1999. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284:1368–72 [Google Scholar]
  73. Kershaw MJ, Moorhouse ER, Bateman R, Reynolds SE, Charnley AK. 73.  1999. The role of destruxins in the pathogenicity of Metarhizium anisopliae for three species of insect. J. Invertebr. Pathol. 74:213–23 [Google Scholar]
  74. Kim H, Woloshuk CP. 74.  2008. Role of AREA, a regulator of nitrogen metabolism, during colonization of maize kernels and fumonisin biosynthesis in Fusarium verticillioides. Fungal Genet. Biol. 45:947–53 [Google Scholar]
  75. Knox BP, Keller NP. 75.  2015. Key players in the regulation of fungal secondary metabolism. Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites 2 S Zeilinger, J-F Martín, C García-Estrada 13–22 New York: Springer-Verlag [Google Scholar]
  76. König CC, Scherlach K, Schroeckh V, Horn F, Nietzsche S. 76.  et al. 2013. Bacterium induces cryptic meroterpenoid pathway in the pathogenic fungus. Aspergillus fumigatus ChemBioChem 14:938–42 [Google Scholar]
  77. Kopke K, Hoff B, Bloemendal S, Katschorowski A, Kamerewerd J, Kück U. 77.  2013. Members of the Penicillium chrysogenum velvet complex play functionally opposing roles in the regulation of penicillin biosynthesis and conidiation. Eukaryot. Cell 12:299–310 [Google Scholar]
  78. Kwon-Chung KJ, Rhodes JC. 78.  1986. Encapsulation and melanin formation as indicators of virulence in Cryptococcus neoformans. Infect. Immun. 51:218–23 [Google Scholar]
  79. Laor D, Cohen A, Kupiec M, Weisman R. 79.  2015. TORC1 regulates developmental responses to nitrogen stress via regulation of the GATA transcription factor Gaf1. mBio 6:e00959 [Google Scholar]
  80. Lee BN, Kroken S, Chou DY, Robbertse B, Yoder OC, Turgeon BG. 80.  2005. Functional analysis of all nonribosomal peptide synthetases in Cochliobolus heterostrophus reveals a factor, NPS6, involved in virulence and resistance to oxidative stress. Eukaryot. Cell 4:545–55 [Google Scholar]
  81. Lee I, Oh JH, Shwab EK, Dagenais TR, Andes D, Keller NP. 81.  2009. HdaA, a class 2 histone deacetylase of Aspergillus fumigatus, affects germination and secondary metabolite production. Fungal Genet. Biol. 46:782–90 [Google Scholar]
  82. Li G, Reinberg D. 82.  2011. Chromatin higher-order structures and gene regulation. Curr. Opin. Genet. Dev. 21:175–86 [Google Scholar]
  83. Liebmann B, Gattung S, Jahn B, Brakhage AA. 83.  2003. cAMP signaling in Aspergillus fumigatus is involved in the regulation of the virulence gene pksP and in defense against killing by macrophages. Mol. Genet. Genom. 269:420–35 [Google Scholar]
  84. Lim FY, Sanchez JF, Wang CC, Keller NP. 84.  2012. Toward awakening cryptic secondary metabolite gene clusters in filamentous fungi. Methods Enzymol. 517:303–24 [Google Scholar]
  85. Liu T, Xu X, Leng W, Xue Y, Dong J, Jin Q. 85.  2014. Analysis of gene expression changes in Trichophyton rubrum after skin interaction. J. Med. Microbiol. 63:642–48 [Google Scholar]
  86. Lobo LS, Luz C, Fernandes EK, Juárez MP, Pedrini N. 86.  2015. Assessing gene expression during pathogenesis: use of qRT-PCR to follow toxin production in the entomopathogenic fungus Beauveria bassiana during infection and immune response of the insect host Triatoma infestans. J. Invertebr. Pathol. 128:14–21 [Google Scholar]
  87. Macheleidt J, Scherlach K, Neuwirth T, Schmidt-Heck W, Strassburger M. 87.  et al. 2015. Transcriptome analysis of cyclic AMP-dependent protein kinase A–regulated genes reveals the production of the novel natural compound fumipyrrole by Aspergillus fumigatus. Mol. Microbiol. 96:148–62 [Google Scholar]
  88. McDonagh A, Fedorova ND, Crabtree J, Yu Y, Kim S. 88.  et al. 2008. Sub-telomere directed gene expression during initiation of invasive aspergillosis. PLOS Pathog. 4:e1000154 [Google Scholar]
  89. Michielse CB, Pfannmüller A, Macios M, Rengers P, Dzikowska A, Tudzynski B. 89.  2014. The interplay between the GATA transcription factors AreA, the global nitrogen regulator and AreB in Fusarium fujikuroi. Mol. Microbiol. 91:472–93 [Google Scholar]
  90. Mihlan M, Homann V, Liu TW, Tudzynski B. 90.  2003. AREA directly mediates nitrogen regulation of gibberellin biosynthesis in Gibberella fujikuroi, but its activity is not affected by NMR. Mol Microbiol 47:4975–91 [Google Scholar]
  91. Miyake K, Kuzuyama T, Horinouchi S, Beppu T. 91.  1990. The A-factor-binding protein of Streptomyces griseus negatively controls streptomycin production and sporulation. J. Bacteriol. 172:3003–8 [Google Scholar]
  92. Montibus M, Ducos C, Bonnin-Verdal MN, Bormann J, Ponts N. 92.  et al. 2013. The bZIP transcription factor Fgap1 mediates oxidative stress response and trichothecene biosynthesis but not virulence in Fusarium graminearum. PLOS ONE 8:e83377 [Google Scholar]
  93. Morton CO, Varga JJ, Hornbach A, Mezger M, Sennefelder H. 93.  et al. 2011. The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. PLOS ONE 6:e16016 [Google Scholar]
  94. Mueller JE, Canze M, Bryk M. 94.  2006. The requirements for COMPASS and Paf1 in transcriptional silencing and methylation of histone H3 in Saccharomyces cerevisiae. Genetics 173:557–67 [Google Scholar]
  95. Müller S, Baldin C, Groth M, Guthke R, Kniemeyer O. 95.  et al. 2012. Comparison of transcriptome technologies in the pathogenic fungus Aspergillus fumigatus reveals novel insights into the genome and MpkA dependent gene expression. BMC Genom. 13:519 [Google Scholar]
  96. Netzker T, Fischer J, Weber J, Mattern DJ, König CC. 96.  et al. 2015. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front. Microbiol. 6:299 [Google Scholar]
  97. Niehaus EM, von Bargen KW, Espino JJ, Pfannmüller A, Humpf HU, Tudzynski B. 97.  2014. Characterization of the fusaric acid gene cluster in Fusarium fujikuroi. Appl. Microbiol. Biotechnol. 98:1749–62 [Google Scholar]
  98. Notz R, Maurhofer M, Dubach H, Haas D, Defago G. 98.  2002. Fusaric acid–producing strains of Fusarium oxysporum alter 2,4-diacetylphloroglucinol biosynthetic gene expression in Pseudomonas fluorescens CHA0 in vitro and in the rhizosphere of wheat. Appl. Environ. Microbiol. 68:2229–35 [Google Scholar]
  99. Nützmann HW, Fischer J, Scherlach K, Hertweck C, Brakhage AA. 99.  2013. Distinct amino acids of histone H3 control secondary metabolism in Aspergillus nidulans. Appl. Environ. Microbiol. 79:6102–9 [Google Scholar]
  100. Nützmann HW, Reyes-Dominguez Y, Scherlach K, Schroeckh V, Horn F. 100.  et al. 2011. Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation. PNAS 108:14282–87 [Google Scholar]
  101. O'Callaghan J, Stapleton PC, Dobson AD. 101.  2006. Ochratoxin A biosynthetic genes in Aspergillus ochraceus are differentially regulated by pH and nutritional stimuli. Fungal Genet. Biol. 43:213–21 [Google Scholar]
  102. Ochiai N, Tokai T, Nishiuchi T, Takahashi-Ando N, Fujimura M, Kimura M. 102.  2007. Involvement of the osmosensor histidine kinase and osmotic stress-activated protein kinases in the regulation of secondary metabolism in Fusarium graminearum. Biochem. Biophys. Res. Commun. 363:639–44 [Google Scholar]
  103. Ogundero VW. 103.  1987. Temperature and aflatoxin production by Aspergillus flavus and A. parasiticus strains from Nigerian groundnuts. J. Basic Microbiol. 27:511–14 [Google Scholar]
  104. Oide S, Moeder W, Krasnoff S, Gibson D, Haas H. 104.  et al. 2006. NPS6 encoding a nonribosomal peptide synthetase involved in siderophore-mediated iron metabolism, is a conserved virulence determinant of plant pathogenic ascomycetes. Plant Cell 18:2836–53 [Google Scholar]
  105. Oosthuizen JL, Gomez P, Ruan J, Hackett TL, Moore MM. 105.  et al. 2011. Dual organism transcriptomics of airway epithelial cells interacting with conidia of Aspergillus fumigatus. PLOS ONE 6:e20527 [Google Scholar]
  106. Palmer JM, Bok JW, Lee S, Dagenais TR, Andes DR. 106.  et al. 2013. Loss of CclA, required for histone 3 lysine 4 methylation, decreases growth but increases secondary metabolite production in Aspergillus fumigatus. PeerJ 1:e4 [Google Scholar]
  107. Palmer JM, Keller NP. 107.  2010. Secondary metabolism in fungi: Does chromosomal location matter?. Curr. Opin. Microbiol. 13:431–46 [Google Scholar]
  108. Palonen EK, Neffling M-R, Raina S, Brandt A, Keshavarz T. 108.  et al. 2014. Butyrolactone I quantification from lovastatin producing Aspergillus terreus using tandem mass spectrometry: evidence of signalling functions. Microorganisms 2:111–27 [Google Scholar]
  109. Park G, Pan S, Borkovich KA. 109.  2008. Mitogen-activated protein kinase cascade required for regulation of development and secondary metabolism in Neurospora crassa. Eukaryot. Cell 7:2113–22 [Google Scholar]
  110. Penalva MA, Tilburn J, Bignell E, Arst HN Jr. 110.  2008. Ambient pH gene regulation in fungi: making connections. Trends Microbiol. 16:291–300 [Google Scholar]
  111. Perrin RM, Fedorova ND, Bok JW, Cramer RA, Wortman JR. 111.  et al. 2007. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PLOS Pathog. 3:e50 [Google Scholar]
  112. Priegnitz BE, Brandt U, Pahirulzaman KA, Dickschat JS, Fleissner A. 112.  2015. The AngFus3 mitogen-activated protein kinase controls hyphal differentiation and secondary metabolism in Aspergillus niger. Eukaryot. Cell 14:602–15 [Google Scholar]
  113. Raina S, Odell M, Keshavarz T. 113.  2010. Quorum sensing as a method for improving sclerotiorin production in Penicillium sclerotiorum. J. Biotechnol. 148:91–98 [Google Scholar]
  114. Rasmussen TB, Skindersoe ME, Bjarnsholt T, Phipps RK, Christensen KB. 114.  et al. 2005. Identity and effects of quorum-sensing inhibitors produced by Penicillium species. Microbiology 151:1325–40 [Google Scholar]
  115. Reverberi M, Gazzetti K, Punelli F, Scarpari M, Zjalic S. 115.  et al. 2012. Aoyap1 regulates OTA synthesis by controlling cell redox balance in Aspergillus ochraceus. Appl. Microbiol. Biotechnol. 95:1293–304 [Google Scholar]
  116. Reverberi M, Zjalic S, Ricelli A, Punelli F, Camera E. 116.  et al. 2008. Modulation of antioxidant defense in Aspergillus parasiticus is involved in aflatoxin biosynthesis: a role for the ApyapA gene. Eukaryot. Cell 7:988–1000 [Google Scholar]
  117. Reyes-Dominguez Y, Boedi S, Sulyok M, Wiesenberger G, Stoppacher N. 117.  et al. 2012. Heterochromatin influences the secondary metabolite profile in the plant pathogen Fusarium graminearum. Fungal Genet. Biol. 49:39–47 [Google Scholar]
  118. Reyes-Dominguez Y, Bok JW, Berger H, Shwab EK, Basheer A. 118.  et al. 2010. Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans. Mol. Microbiol. 76:1376–86 [Google Scholar]
  119. Rispail N, Soanes DM, Ant C, Czajkowski R, Grünler A. 119.  et al. 2009. Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi. Fungal Genet. Biol. 46:287–98 [Google Scholar]
  120. Rodríguez-Ortiz R, Mehta BJ, Avalos J, Limón MC. 120.  2010. Stimulation of bikaverin production by sucrose and by salt starvation in Fusarium fujikuroi. Appl. Microbiol. Biotechnol. 85:1991–2000 [Google Scholar]
  121. Roze LV, Arthur AE, Hong SY, Chanda A, Linz JE. 121.  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. 66:713–26 [Google Scholar]
  122. Roze LV, Beaudry RM, Keller NP, Linz JE. 122.  2004. Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in Aspergillus parasiticus. Mycopathologia 158:219–32 [Google Scholar]
  123. Roze LV, Koptina AV, Laivenieks M, Beaudry RM, Jones DA. 123.  et al. 2011. Willow volatiles influence growth, development, and secondary metabolism in Aspergillus parasiticus. Appl. Microbiol. Biotechnol. 92:359–70 [Google Scholar]
  124. Roze LV, Miller MJ, Rarick M, Mahanti N, Linz JE. 124.  2004. A novel cAMP-response element, CRE1, modulates expression of nor-1 in Aspergillus parasiticus. J. Biol. Chem. 279:27428–39 [Google Scholar]
  125. Ruiz-Sanchez E, O'Donnell MJ. 125.  2012. Effects of the microbial metabolite destruxin A on ion transport by the gut and renal epithelia of Drosophila melanogaster. Arch. Insect Biochem. Physiol. 80:109–22 [Google Scholar]
  126. Rutledge PJ, Challis GL. 126.  2015. Discovery of microbial natural products by activation of silent biosynthetic gene clusters. Nat. Rev. Microbiol. 13:509–23 [Google Scholar]
  127. Sanchez JF, Somoza AD, Keller NP, Wang CC. 127.  2012. Advances in Aspergillus secondary metabolite research in the post-genomic era. Nat. Prod. Rep. 29:351–71 [Google Scholar]
  128. Scherlach K, Nützmann HW, Schroeckh V, Dahse HM, Brakhage AA, Hertweck C. 128.  2011. Cytotoxic pheofungins from an engineered fungus impaired in posttranslational protein modification. Angew. Chem. 50:9843–47 [Google Scholar]
  129. Schmitt EK, Kück U. 129.  2000. The fungal CPCR1 protein, which binds specifically to β-lactam biosynthesis genes, is related to human regulatory factor X transcription factors. J. Biol. Chem. 275:9348–57 [Google Scholar]
  130. Schrettl M, Bignell E, Kragl C, Sabiha Y, Loss O. 130.  et al. 2007. Distinct roles for intra- and extracellular siderophores during Aspergillus fumigatus infection. PLOS Pathog. 3:1195–207 [Google Scholar]
  131. Schroeckh V, Scherlach K, Nützmann HW, Shelest E, Schmidt-Heck W. 131.  et al. 2009. Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. PNAS 106:14558–63 [Google Scholar]
  132. Shimizu K, Hicks JK, Huang TP, Keller NP. 132.  2003. Pka, Ras and RGS protein interactions regulate activity of AflR, a Zn(II)2Cys6 transcription factor in Aspergillus nidulans. Genetics 165:1095–104 [Google Scholar]
  133. Shimizu M, Masuo S, Fujita T, Doi Y, Kamimura Y, Takaya N. 133.  2012. Hydrolase controls cellular NAD, sirtuin, and secondary metabolites. Mol. Cell. Biol. 32:3743–55 [Google Scholar]
  134. Shwab EK, Bok JW, Tribus M, Galehr J, Graessle S, Keller NP. 134.  2007. Histone deacetylase activity regulates chemical diversity in Aspergillus. Eukaryot. Cell 6:1656–64 [Google Scholar]
  135. Song Z, Bakeer W, Marshall JW, Yakasai AA, Khalid RM. 135.  et al. 2015. Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae. Chem. Sci. 6:4837–45 [Google Scholar]
  136. Soukup AA, Chiang YM, Bok JW, Reyes-Dominguez Y, Oakley BR. 136.  et al. 2012. Overexpression of the Aspergillus nidulans histone 4 acetyltransferase EsaA increases activation of secondary metabolite production. Mol. Microbiol. 86:314–30 [Google Scholar]
  137. Spiteller P. 137.  2015. Chemical ecology of fungi. Nat. Prod. Rep. 32:971–93 [Google Scholar]
  138. Stergiopoulos I, Collemare J, Mehrabi R, De Wit PJ. 138.  2013. Phytotoxic secondary metabolites and peptides produced by plant pathogenic Dothideomycete fungi. FEMS Microbiol. Rev. 37:67–93 [Google Scholar]
  139. Stinnett SM, Espeso EA, Cobeno L, Araujo-Bazan L, Calvo AM. 139.  2007. Aspergillus nidulans VeA subcellular localization is dependent on the importin alpha carrier and on light. Mol. Microbiol. 63:242–55 [Google Scholar]
  140. Stocker-Worgotter E. 140.  2008. Metabolic diversity of lichen-forming ascomycetous fungi: culturing, polyketide and shikimate metabolite production, and PKS genes. Nat. Prod. Rep. 25:188–200 [Google Scholar]
  141. Stoll D, Schmidt-Heydt M, Geisen R. 141.  2013. Differences in the regulation of ochratoxin A by the HOG pathway in Penicillium and Aspergillus in response to high osmolar environments. Toxins 5:1282–98 [Google Scholar]
  142. Studt L, Schmidt FJ, Jahn L, Sieber CM, Connolly LR. 142.  et al. 2013. Two histone deacetylases, FfHda1 and FfHda2, are important for Fusarium fujikuroi secondary metabolism and virulence. Appl. Environ. Microbiol. 79:7719–34 [Google Scholar]
  143. Sueiro-Olivares M, Fernandez-Molina JV, Abad-Diaz-de-Cerio A, Gorospe E, Pascual E. 143.  et al. 2015. Aspergillus fumigatus transcriptome response to a higher temperature during the earliest steps of germination monitored using a new customized expression microarray. Microbiology 161:490–502 [Google Scholar]
  144. Sugui JA, Kim HS, Zarember KA, Chang YC, Gallin JI. 144.  et al. 2008. Genes differentially expressed in conidia and hyphae of Aspergillus fumigatus upon exposure to human neutrophils. PLOS ONE 3:e2655 [Google Scholar]
  145. Tag A, Hicks J, Garifullina G, Ake C Jr, Phillips TD. 145.  et al. 2000. G-protein signalling mediates differential production of toxic secondary metabolites. Mol. Microbiol. 38:658–65 [Google Scholar]
  146. Thön M, Al Abdallah Q, Hortschansky P, Scharf DH, Eisendle M. 146.  et al. 2010. The CCAAT-binding complex coordinates the oxidative stress response in eukaryotes. Nucleic Acids Res. 38:1098–113 [Google Scholar]
  147. Tilburn J, Sarkar S, Widdick DA, Espeso EA, Orejas M. 147.  et al. 1995. The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J. 14:779–90 [Google Scholar]
  148. Tsuge T, Harimoto Y, Akimitsu K, Ohtani K, Kodama M. 148.  et al. 2013. Host-selective toxins produced by the plant pathogenic fungus Alternaria alternata. FEMS Microbiol. Rev. 37:44–66 [Google Scholar]
  149. Tsuji G, Kenmochi Y, Takano Y, Sweigard J, Farrall L. 149.  et al. 2000. Novel fungal transcriptional activators, Cmr1p of Colletotrichum lagenarium and Pig1p of Magnaporthe grisea, contain Cys2His2 zinc finger and Zn(II)2Cys6 binuclear cluster DNA-binding motifs and regulate transcription of melanin biosynthesis genes in a developmentally specific manner. Mol. Microbiol. 38:940–54 [Google Scholar]
  150. Tudzynski B. 150.  2014. Nitrogen regulation of fungal secondary metabolism in fungi. Front. Microbiol. 5:656 [Google Scholar]
  151. Tudzynski B, Homann V, Feng B, Marzluf GA. 151.  1999. Isolation, characterization and disruption of the areA nitrogen regulatory gene of Gibberella fujikuroi. Mol. Gen. Genet. 261:106–14 [Google Scholar]
  152. Tyc O, van den Berg M, Gerards S, van Veen JA, Raaijmakers JM. 152.  et al. 2014. Impact of interspecific interactions on antimicrobial activity among soil bacteria. Front. Microbiol. 5:567 [Google Scholar]
  153. Valero-Jiménez CA, Wiegers H, Zwaan BJ, Koenraadt CJ, van Kan JA. 153.  2016. Genes involved in virulence of the entomopathogenic fungus Beauveria bassiana. J. Invertebr. Pathol. 133:41–49 [Google Scholar]
  154. Valiante V, Jain R, Heinekamp T, Brakhage AA. 154.  2009. The MpkA MAP kinase module regulates cell wall integrity signaling and pyomelanin formation in Aspergillus fumigatus. Fungal Genet. Biol. 46:909–18 [Google Scholar]
  155. Valiante V, Macheleidt J, Föge M, Brakhage AA. 155.  2015. The Aspergillus fumigatus cell wall integrity signaling pathway: drug target, compensatory pathways, and virulence. Front. Microbiol. 6:325 [Google Scholar]
  156. Venkatesh S, Workman JL. 156.  2015. Histone exchange, chromatin structure and the regulation of transcription. Nat. Rev. Mol. Cell. Biol. 16:178–89 [Google Scholar]
  157. Vödisch M, Scherlach K, Winkler R, Hertweck C, Braun HP. 157.  et al. 2011. Analysis of the Aspergillus fumigatus proteome reveals metabolic changes and the activation of the pseurotin A biosynthesis gene cluster in response to hypoxia. J. Proteome Res. 10:2508–24 [Google Scholar]
  158. Wang Q, Xu L. 158.  2012. Beauvericin, a bioactive compound produced by fungi: a short review. Molecules 17:2367–77 [Google Scholar]
  159. Wartenberg D, Vödisch M, Kniemeyer O, Albrecht-Eckardt D, Scherlach K. 159.  et al. 2012. Proteome analysis of the farnesol-induced stress response in Aspergillus nidulans: the role of a putative dehydrin. J. Proteom. 75:4038–49 [Google Scholar]
  160. Waters CM, Bassler BL. 160.  2005. Quorum sensing: cell-to-cell communication in bacteria. Annu. Rev. Cell Dev. Biol. 21:319–46 [Google Scholar]
  161. Wiemann P, Guo CJ, Palmer JM, Sekonyela R, Wang CC, Keller NP. 161.  2013. Prototype of an intertwined secondary-metabolite supercluster. PNAS 110:17065–70 [Google Scholar]
  162. Wiemann P, Willmann A, Straeten M, Kleigrewe K, Beyer M. 162.  et al. 2009. Biosynthesis of the red pigment bikaverin in Fusarium fujikuroi: genes, their function and regulation. Mol. Microbiol. 72:931–46 [Google Scholar]
  163. Williams RB, Henrikson JC, Hoover AR, Lee AE, Cichewicz RH. 163.  2008. Epigenetic remodeling of the fungal secondary metabolome. Org. Biomol. Chem. 6:1895–97 [Google Scholar]
  164. Yin W, Keller NP. 164.  2011. Transcriptional regulatory elements in fungal secondary metabolism. J. Microbiol. 49:329–39 [Google Scholar]
  165. Yin WB, Amaike S, Wohlbach DJ, Gasch AP, Chiang YM. 165.  et al. 2012. An Aspergillus nidulans bZIP response pathway hardwired for defensive secondary metabolism operates through aflR. Mol. Microbiol. 83:1024–34 [Google Scholar]
  166. Zou Z, Du D, Zhang Y, Zhang J, Niu G, Tan H. 166.  2014. A γ-butyrolactone-sensing activator/repressor, JadR3, controls a regulatory mini-network for jadomycin biosynthesis. Mol. Microbiol. 94:490–505 [Google Scholar]
  167. Zutz C, Gacek A, Sulyok M, Wagner M, Strauss J, Rychli K. 167.  2013. Small chemical chromatin effectors alter secondary metabolite production in Aspergillus clavatus. Toxins 5:1723–41 [Google Scholar]
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Regulation and Role of Fungal Secondary Metabolites
Annual Review of Genetics 50, 371 (2016); https://doi.org/10.1146/annurev-genet-120215-035203
/content/journals/10.1146/annurev-genet-120215-035203
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