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Epigenetic Regulation of Secondary Metabolite Biosynthetic Genes in Fungi

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Biocommunication of Fungi

Abstract

Many fungi are prolific producers of secondary metabolites. These compounds are thought to fill a variety of ecologically relevant functions including participating in chemical sensing systems and communicating with other organisms in their surroundings. In order for natural products to operate effectively, the host organisms must maintain control over their expression. Epigenetic processes have emerged as important contributors to the regulation of secondary metabolite expression in fungi. Several examples highlighting the range of secondary metabolites whose production is controlled wholly or in part by epigenetic processes are presented. Recently reported cases demonstrating how insights into epigenetic control mechanisms can improve the production and diversification of secondary metabolite production are also examined.

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References

  • Asai T, Chung Y-M, Sakurai H, Ozeki T, Chang F-R, Yamashita K, Oshima Y (2011a) Tenuipyrone, a novel skeletal polyketide from the entomopathogenic fungus, Isaria tenuipes, cultivated in the presence of epigenetic modifiers. Org Lett 14(2):513–515. doi:10.1021/ol203097b

    Article  PubMed  Google Scholar 

  • Asai T, Yamamoto T, Oshima Y (2011b) Histone deacetylase inhibitor induced the production of three novel prenylated tryptophan analogs in the entomopathogenic fungus, Torrubiella luteorostrata. Tetrahedron Lett 52:7042–7045

    Article  CAS  Google Scholar 

  • Asai T, Yamamoto T, Chung Y-M, Chang F-R, Wu Y-C, Yamashita K, Oshima Y (2012) Aromatic polyketide glycosides from an entomopathogenic fungus, Cordyceps indigotica. Tetrahedron Lett 53:277–280

    Article  CAS  Google Scholar 

  • Ayers S, Zink DL, Mohn K, Powell JS, Brown CM, Bills G, Grund A, Thompson D, Singh SB (2010) Anthelmintic constituents of Clonostachys candelabrum. J Antibiot 63:119–122

    Article  PubMed  CAS  Google Scholar 

  • Bok JW, Chiang Y-M, Szewczyk E, Reyes-Dominguez Y, Davidson AD, Sanchez JF, Lo H-C, Watanabe K, Strauss J, Oakley BR, Wang CCC, Keller NP (2009) Chromatin-level regulation of biosynthetic gene clusters. Nat Chem Biol 5:462–464

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Brosch G, Loidl P, Graessle S (2008) Histone modifications and chromatin dynamics: a focus on filamentous fungi. FEMS Microbiol Rev 32:409–439

    Article  PubMed  CAS  Google Scholar 

  • Chiang YM, Lee KH, Sanchez JF, Keller NP, Wang CC (2009) Unlocking fungal cryptic natural products. Nat Prod Commun 4:1505–1510

    PubMed  CAS  Google Scholar 

  • Cichewicz RH (2010) Epigenome manipulation as a pathway to new natural product scaffolds and their congeners. Nat Prod Rep 27:11–22

    Article  PubMed  CAS  Google Scholar 

  • Cichewicz RH, Henrikson JC, Wang X, Branscum KM (2010) Strategies for accessing microbial secondary metabolites from silent biosynthetic pathways. In: Baltz RH, Demain AL, Davies JE (eds) Manual of industrial microbiology and biotechnology, 3rd edn. ASM Press, Washington, DC, pp 78–95

    Google Scholar 

  • Davies J, Ryan KS (2011) Introducing the parvome: bioactive compounds in the microbial world. ACS Chem Biol 7:252–259. doi:10.1021/cb200337h

  • Emre NC, Berger SL (2006) Histone post-translational modifications regulate transcription and silent chromatin in Saccharomyces cerevisiae. Ernst Schering Res Found Workshop 57:127–153

    Google Scholar 

  • Fisch K, Gillaspy A, Gipson M, Henrikson J, Hoover A, Jackson L, Najar F, Wägele H, Cichewicz R (2009) Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger. J Ind Microbiol Biotechnol 36:1199–1213

    Article  PubMed  CAS  Google Scholar 

  • Hertweck C (2009) Hidden biosynthetic treasures brought to light. Nat Chem Biol 5:450–452

    Article  PubMed  CAS  Google Scholar 

  • Kumazawa S, Kanda M, Utagawa M, Chiba N, Ohtani H, Mikawa T (2003) MK7924, a novel metabolite with nematocidal activity from Coronophora gregaria. J Antibiot 56:652–654

    Article  PubMed  CAS  Google Scholar 

  • Lee I, Oh J-H, Keats Shwab E, Dagenais TRT, Andes D, Keller NP (2009) HdaA, a class 2 histone deacetylase of Aspergillus fumigatus, affects germination and secondary metabolite production. Fungal Genet Biol 46:782–790

    Article  PubMed  CAS  Google Scholar 

  • Martienssen RA, Kloc A, Slotkin RK, Tanurdžić M (2008) Epigenetic inheritance and reprogramming in plants and fission yeast. Cold Spring Harb Symp Quant Biol 73:265–271

    Article  PubMed  CAS  Google Scholar 

  • McDonagh A, Fedorova ND, Crabtree J, Yu Y, Kim S, Chen D, Loss O, Cairns T, Goldman G, Armstrong-James D, Haynes K, Haas H, Schrettl M, May G, Nierman WC, Bignell E (2008) Sub-telomere directed gene expression during initiation of invasive aspergillosis. PLoS Pathog 4:e1000154

    Article  PubMed  Google Scholar 

  • Nützmann H-W, Reyes-Dominguez Y, Scherlach K, Schroeckh V, Horn F, Gacek A, Schümann J, Hertweck C, Strauss J, Brakhage AA (2011) Bacteria-induced natural product formation in the fungus Aspergillus nidulans requires Saga/Ada-mediated histone acetylation. Proc Natl Acad Sci USA 108:14282–14287

    Article  PubMed  Google Scholar 

  • Palmer JM, Keller NP (2010) Secondary metabolism in fungi: does chromosomal location matter? Curr Opin Microbiol 13:431–436

    Article  PubMed  CAS  Google Scholar 

  • Perrin RM, Fedorova ND, Bok JW, Cramer RA Jr, Wortman JR, Kim HS, Nierman WC, Keller NP (2007) Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PLoS Pathog 3:e50

    Article  PubMed  Google Scholar 

  • Pettit RK (2011) Small-molecule elicitation of microbial secondary metabolites. Microb Biotechnol 4:471–478

    Article  PubMed  CAS  Google Scholar 

  • Reyes-Dominguez Y, Bok JW, Berger H, Shwab EK, Basheer A, Gallmetzer A, Scazzocchio C, Keller N, Strauss J (2010) Heterochromatic marks are associated with the repression of secondary metabolism clusters in Aspergillus nidulans. Mol Microbiol 76:1376–1386

    Article  PubMed  CAS  Google Scholar 

  • Reyes-Dominguez Y, Boedi S, Sulyok M, Wiesenberger G, Stoppacher N, Krska R, Strauss J (2011) Heterochromatin influences the secondary metabolite profile in the plant pathogen Fusarium graminearum. Fungal Genet Biol 49:39–47. doi:10.1016/j.fgb.2011.11.002

    Article  PubMed  Google Scholar 

  • Scherlach K, Hertweck C (2009) Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 7:1753–1760

    Article  PubMed  CAS  Google Scholar 

  • Schroeckh V, Scherlach K, Nützmann H-W, Shelest E, Schmidt-Heck W, Schuemann J, Martin K, Hertweck C, Brakhage AA (2009) Intimate bacterial–fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc Natl Acad Sci USA 106:14558–14563

    Article  PubMed  CAS  Google Scholar 

  • Stimpson KM, Sullivan BA (2010) Epigenomics of centromere assembly and function. Curr Opin Cell Biol 22:772–780

    Article  PubMed  CAS  Google Scholar 

  • Strauss J, Reyes-Dominguez Y (2011) Regulation of secondary metabolism by chromatin structure and epigenetic codes. Fungal Genet Biol 48:62–69

    Article  PubMed  CAS  Google Scholar 

  • Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476

    Article  PubMed  CAS  Google Scholar 

  • Ul-Hassan SR, Strobel GA, Booth E, Knighton B, Floerchinger C, Sears J (2012) Modulation of volatile organic compound formation in the mycodiesel-producing endophyte – Hypoxylon sp. CI-4. Microbiology 158:465–473. doi:10.1099/mic.0.054643-0

    Article  PubMed  Google Scholar 

  • Vervoort HC, DraÅ¡ković M, Crews P (2010) Histone deacetylase inhibitors as a tool to up-regulate new fungal biosynthetic products: isolation of EGM-556, a cyclodepsipeptide, from Microascus sp. Org Lett 13:410–413

    Article  PubMed  Google Scholar 

  • Wang X, Sena Filho JG, Hoover AR, King JB, Ellis TK, Powell DR, Cichewicz RH (2010) Chemical epigenetics alters the secondary metabolite composition of guttate excreted by an Atlantic-Forest-soil-derived Penicillium citreonigrum. J Nat Prod 73:942–948

    Article  PubMed  CAS  Google Scholar 

  • Williams RB, Henrikson JC, Hoover AR, Lee AE, Cichewicz RH (2008) Epigenetic remodeling of the fungal secondary metabolome. Org Biomol Chem 6:1895–1897

    Article  PubMed  CAS  Google Scholar 

  • Yakasai AA, Davison J, Wasil Z, Halo LM, Butts CP, Lazarus CM, Bailey AM, Simpson TJ, Cox RJ (2011) Nongenetic reprogramming of a fungal highly reducing polyketide synthase. J Am Chem Soc 133:10990–10998

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Robert Cichewicz .

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Cichewicz, R. (2012). Epigenetic Regulation of Secondary Metabolite Biosynthetic Genes in Fungi. In: Witzany, G. (eds) Biocommunication of Fungi. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4264-2_4

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