Advertisement

Metabolomics and Secondary Metabolite Profiling of Filamentous Fungi

  • Bernhard KlugerEmail author
  • Sylvia Lehner
  • Rainer Schuhmacher
Chapter
Part of the Fungal Biology book series (FUNGBIO)

Abstract

Driven by significant technical developments in analytical instrumentation and the tremendous advances in biological sciences, a change in paradigm from reductionist to holistic approaches for the study of filamentous fungi can be observed currently. This development is also reflected by the emergence of metabolomics as the latest of the so-called -omics disciplines. Metabolomics , the scientific discipline dealing with the determination of the low-molecular-weight complement of biological systems is increasingly being used to investigate the biochemical composition of fungi and their biological interactions. This chapter introduces the general concept of metabolomics and summarizes the analytical approaches used for the study of fungal exo- and endo-metabolomes. Current applications in fungal metabolomics and metabolite profiling such as chemotaxonomical classification, the search and production of novel beneficial secondary metabolites as well the dissection of host–fungus interactions are presented. Finally, novel emerging approaches for the improved fungal metabolomics, such as the use of stable isotope labeled biological samples and tracer metabolites and novel techniques, that enable spatial and temporal dissection of metabolite production, are briefly summarized.

Keywords

Liquid chromatography-mass spectrometry (LC-MS) Gas chromatography-mass spectrometry (GC-MS) Untargeted metabolite profiling Targeted metabolite profiling Exometabolome Endometabolome Chemotaxonomy Secondary metabolites Host–fungus interactions 

Notes

Acknowledgements

The authors would like to thank the Austrian Science Fund (project SFB Fusarium 3706-B11) for financial support. Thanks are also offered to Benedikt Warth for his valuable comments on the draft of this manuscript as well as Maria Doppler and Christoph Bueschl for their kind assistance in preparing the figures. The presented work contributes in part to the PhD thesis of Bernhard Kluger.

References

  1. 1.
    Carlile JM, Watkinson SC, Gooday GW (2001) The fungi. 2nd edn. Elsevier, London. ISBN-13: 978-0-12-738446-7Google Scholar
  2. 2.
    Kliebenstein DJ (2004) Secondary metabolites and plant/environment interactions: a view through Arabidopsis thaliana tinged glasses. Plant Cell Environ 27(6):675–684CrossRefGoogle Scholar
  3. 3.
    Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism—from biochemistry to genomics. Nat Rev Micro 3(12):937–947CrossRefGoogle Scholar
  4. 4.
    Calvo AM, Wilson RA, Bok JW, Keller NP (2002) Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev 66(3):447–459PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Karlovsky P (2012) Secondary Metabolites in Soil Ecology. In: Karlovsky P (ed) Soil Biology, vol. 14. Springer, Berlin Heidelberg, pp 1–19Google Scholar
  6. 6.
    Martín JF, Gutiérrez S, Aparicio JF (2000) Secondary metabolites. In: Lederberg J (ed) En: encyclopedia of microbiology, vol. 4, 2nd ed. Academic Press, San Diego, pp. 213–236Google Scholar
  7. 7.
    Fiehn O (2002) Metabolomics—the link between genotypes and phenotypes. Plant Mol Biol 48(1):155–171PubMedCrossRefGoogle Scholar
  8. 8.
    Goodacre R (2005) Metabolomics—the way forward. Metabolomics 1(1):1–2CrossRefGoogle Scholar
  9. 9.
    Schuhmacher R, Krska R, Weckwerth W, Goodacre R (2013) Metabolomics and metabolite profiling. Anal Bioanal Chem 405(15):5003–5004PubMedCrossRefGoogle Scholar
  10. 10.
    Patti GJ, Yanes O, Siuzdak G (2012) Innovation: metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol 13(4):263–269PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Bueschl C, Kluger B, Lemmens M, Adam G, Wiesenberger G, Maschietto V, Marocco A, Strauss J, Bödi S, Thallinger GG, Krska R, Schuhmacher R (2014) A novel stable isotope labelling assisted workflow for improved untargeted LC-HRMS based metabolomics research. Metabolomics 10(4):754–769PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Boccard J, Veuthey J-L, Rudaz S (2010) Knowledge discovery in metabolomics: an overview of MS data handling. J Sep Sci 33(3):290–304PubMedCrossRefGoogle Scholar
  13. 13.
    Katajamaa M, Orešič M (2007) Data processing for mass spectrometry-based metabolomics. J Chromatogr A 1158(1–2):318–328PubMedCrossRefGoogle Scholar
  14. 14.
    Sugimoto M, Kawakami M, Robert M, Soga T, Tomita M (2012) Bioinformatics tools for mass spectroscopy-based metabolomic data processing and analysis. Curr Bioinform 7(1):96–108PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Fiehn O (2001) Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comp Funct Genomics 2(3):155–168PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Goodacre R, Vaidyanathan S, Dunn WB, Harrigan GG, Kell DB (2005) Metabolomics by numbers: acquiring and understanding global metabolite data. Trends Biotechnol 22(5):245–252CrossRefGoogle Scholar
  17. 17.
    Dettmer K, Aronov PA, Hammock BD (2007) Mass spectrometry-based metabolomics. Mass Spectrom Rev 26(1):51–78PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Kell DB, Brown M, Davey HM, Dunn WB, Spasic I, Oliver SG (2005) Metabolic footprinting and systems biology: the medium is the message. Nat Rev Micro 3(7):557–565CrossRefGoogle Scholar
  19. 19.
    Thrane U, Anderson B, Frisvad J, Smedsgaard J (2007) The exo-metabolome in filamentous fungi. In: Nielsen J, Jewett M (eds) Metabolomics. Springer, Berlin, pp 235–52CrossRefGoogle Scholar
  20. 20.
    Werf MJvd, Overkamp KM, Muilwijk B, Coulier L, Hankemeier T (2007) Microbial metabolomics: toward a platform with full metabolome coverage. Anal Biochem 370(1):17–25PubMedCrossRefGoogle Scholar
  21. 21.
    Mashego M, Rumbold K, De Mey M, Vandamme E, Soetaert W, Heijnen J (2007) Microbial metabolomics: past, present and future methodologies. Biotechnol Lett 29(1):1–16PubMedCrossRefGoogle Scholar
  22. 22.
    Xu Y-J, Wang C, Ho WE, Ong CN (2014) Recent developments and applications of metabolomics in microbiological investigations. TrAC Trends Anal Chem 56(0):37–48CrossRefGoogle Scholar
  23. 23.
    Klitgaard A, Iversen A, Andersen M, Larsen T, Frisvad J, Nielsen K (2014) Aggressive dereplication using UHPLC–DAD–QTOF: screening extracts for up to 3000 fungal secondary metabolites. Anal Bioanal Chem 406(7):1933–1943PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Wehrens R, Carvalho E, Masuero D, de Juan A, Martens S (2013) High-throughput carotenoid profiling using multivariate curve resolution. Anal Bioanal Chem 405(15):5075–5086PubMedCrossRefGoogle Scholar
  25. 25.
    Villas-Bôas SG, Mas S, Åkesson M, Smedsgaard J, Nielsen J (2005) Mass spectrometry in metabolome analysis. Mass Spectrom Rev 24(5):613–646PubMedCrossRefGoogle Scholar
  26. 26.
    Villas-Bôas SG, Rasmussen S, Lane GA (2005) Metabolomics or metabolite profiles? Trends Biotechnol 23(8):385–386PubMedCrossRefGoogle Scholar
  27. 27.
    Pan Z, Raftery D (2007) Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Anal Bioanal Chem 387(2):525–527PubMedCrossRefGoogle Scholar
  28. 28.
    Degtyarenko K, Hastings J, de Matos P, Ennis M (2009) ChEBI: an open bioinformatics and cheminformatics resource. Current protocols in bioinformatics: John Wiley & Sons, Inc. Supplement 26, unit 14.9Google Scholar
  29. 29.
    Bolton E, Wang Y, Thiessen PA, Bryant SH (2008) PubChem: integrated platform of small molecules and biological activities. Chapter 12 IN Annual Reports in Computational Chemistry, vol 4. Elsevier, Oxford, pp 217–240Google Scholar
  30. 30.
    Laatsch H (2012) AntiBase 2012: The Natural Compound Identifier. Wiley-VCH Verlag GmbH & Co. KGaA, ISBN: 978-3527334063Google Scholar
  31. 31.
    Sumner L, Amberg A, Barrett D, Beale M, Beger R, Daykin C et al (2007) Proposed minimum reporting standards for chemical analysis. Metabolomics 3(3):211–221PubMedCentralPubMedCrossRefGoogle Scholar
  32. 32.
    Dunn WB, Erban A, Weber RJM, Creek DJ, Brown M, Breitling R et al (2013) Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics. Metabolomics 9(1):44–66CrossRefGoogle Scholar
  33. 33.
    Stein SE (1999) An integrated method for spectrum extraction and compound identification from gas chromatography/mass spectrometry data. J Am Soc Mass Spectrom 10(8):770–781CrossRefGoogle Scholar
  34. 34.
    Hiller K, Hangebrauk J, Jäger C, Spura J, Schreiber K, Schomburg D (2009) MetaboliteDetector: comprehensive analysis tool for targeted and nontargeted GC/MS based metabolome analysis. Anal Chem 81(9):3429–3439PubMedCrossRefGoogle Scholar
  35. 35.
    Wiley Registry 10th Edition/ NIST 2012 Mass Spectral Library. 2013. Wiley New York, ISBN: 978-1-118-61611-6Google Scholar
  36. 36.
    Jeleń HH (2003) Use of solid phase microextraction (SPME) for profiling fungal volatile metabolites. Lett Appl Microbiol 36(5):263–267PubMedCrossRefGoogle Scholar
  37. 37.
    Stoppacher N, Kluger B, Zeilinger S, Krska R, Schuhmacher R (2010) Identification and profiling of volatile metabolites of the biocontrol fungus Trichoderma atroviride by HS-SPME-GC-MS. J Microbiol Methods 81(2):187–193PubMedCrossRefGoogle Scholar
  38. 38.
    Kluger B, Zeilinger S, Wiesenberger G, Schoefbeck D, Schuhmacher R (2013) Detection and identification of fungal volatile organic carbons. In: Gupta VK, Tuohy MG, Ayyachamy M, Turner KM, O’Donovan A (eds). Laboratory protocols in fungal biology. Springer, New York, pp 455–465Google Scholar
  39. 39.
    Frisvad JC, Larsen TO, de Vries R, Meijer M, Houbraken J, Cabañes FJ et al (2007) Secondary metabolite profiling, growth profiles and other tools for species recognition and important Aspergillus mycotoxins. Stud Mycol 59(0):31–37PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    Reithner B, Schuhmacher R, Stoppacher N, Pucher M, Brunner K, Zeilinger S (2007) Signaling via the Trichoderma atroviride mitogen-activated protein kinase Tmk1 differentially affects mycoparasitism and plant protection. Fungal Genet Biol 44(11):1123–1133PubMedCrossRefGoogle Scholar
  41. 41.
    Gummer JA, Krill C, Du Fall L, Waters OC, Trengove R, Oliver R et al (2012) Metabolomics protocols for filamentous fungi. In: Bolton MD, Thomma BPHJ (eds). Plant fungal pathogens—Methods in molecular biology, vol. 835. Humana Press, New York, pp 237–254Google Scholar
  42. 42.
    World Health Organisation Regional Office for Europe Copenhagen (1989) Indoor air quality: organic pollutants. Report on a WHO meeting Berlin (West) 23–27 August 1987Google Scholar
  43. 43.
    Halket JM, Waterman D, Przyborowska AM, Patel RKP, Fraser PD, Bramley PM (2005) Chemical derivatization and mass spectral libraries in metabolic profiling by GC/MS and LC/MS/MS. J Exp Bot 56(410):219–243PubMedCrossRefGoogle Scholar
  44. 44.
    Tholl D, Boland W, Hansel A, Loreto F, Roese USR, Schnitzler J-P (2006) Practical approaches to plant volatile analysis. Plant J 45:540–560PubMedCrossRefGoogle Scholar
  45. 45.
    Rubiolo P, Sgorbini B, Liberto E, Cordero C, Bicchi C (2010) Analysis of the plant volatile fraction. In: Herrmann A (ed) The chemistry and biology of volatiles. Wiley, Chichester, pp 49–93CrossRefGoogle Scholar
  46. 46.
    Rowan DD (2001) Volatile metabolites. Metabolites 1(1):41–63CrossRefGoogle Scholar
  47. 47.
    Zeilinger S, Schuhmacher R (2013) Volatile organic metabolites of Trichoderma spp.: biosynthesis, biology and analytics. In: Mukherjee PK, Horwitz BA, Shankar Singh U, Mukherjee M, Schmoll M (eds). Trichoderma—biology and Applications. CAB International, Wallingford, pp 110–127Google Scholar
  48. 48.
    Roessner U, Dias DA (2013) Plant tissue extraction for metabolomics. Methods Mol Biol 1055:21–28PubMedGoogle Scholar
  49. 49.
    Smart KF, Aggio RBM, Van Houtte JR, Villas-Boas SG (2010) Analytical platform for metabolome analysis of microbial cells using methyl chloroformate derivatization followed by gas chromatography-mass spectrometry. Nat Protocols 5(10):1709–1729CrossRefGoogle Scholar
  50. 50.
    Koek MM, Muilwijk B, van der Werf MJ, Hankemeier T (2006) Microbial metabolomics with gas chromatography/mass spectrometry. Anal Chem 78(4):1272–1281PubMedCrossRefGoogle Scholar
  51. 51.
    Madla S, Miura D, Wariishi H (2012) Optimization of extraction method for GC-MS based metabolomics for filamentous fungi. J Microbial Biochem Technol 4:005–009CrossRefGoogle Scholar
  52. 52.
    Wu Z, Huang Z, Lehmann R, Zhao C, Xu G (2009) The application of chromatography-mass spectrometry: methods to metabonomics. Chroma 69(1):23–32CrossRefGoogle Scholar
  53. 53.
    Klavins K, Drexler H, Hann S, Koellensperger G (2014) Quantitative metabolite profiling utilizing parallel column analysis for simultaneous reversed-phase and hydrophilic interaction liquid chromatography separations combined with tandem mass spectrometry. Anal Chem 86(9):4145–4150PubMedCrossRefGoogle Scholar
  54. 54.
    Abia WA, Simo GN, Warth B, Sulyok M, Krska R, Tchana A, Moundipa PF (2013) Determination of multiple mycotoxins levels in poultry feeds from Cameroon. Jpn J Vet Res 61:S33–39PubMedGoogle Scholar
  55. 55.
    Lehner SM, Neumann NKN, Sulyok M, Lemmens M, Krska R, Schuhmacher R (2011) Evaluation of LC-high-resolution FT-Orbitrap MS for the quantification of selected mycotoxins and the simultaneous screening of fungal metabolites in food. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28(10):1457–1468PubMedCrossRefGoogle Scholar
  56. 56.
    Ates E, Godula M, Stroka J, Senyuva H (2014) Screening of plant and fungal metabolites in wheat, maize and animal feed using automated on-line clean-up coupled to high resolution mass spectrometry. Food Chem 142(0):276–284PubMedCrossRefGoogle Scholar
  57. 57.
    Chokkathukalam A, Jankevics A, Creek DJ, Achcar F, Barrett MP, Breitling R (2013) mzMatch–ISO: an R tool for the annotation and relative quantification of isotope-labelled mass spectrometry data. Bioinformatics 29(2):281–283PubMedCentralPubMedCrossRefGoogle Scholar
  58. 58.
    Huang X, Chen Y Jr, Cho K, Nikolskiy I, Crawford PA, Patti GJ (2014) X13CMS: global tracking of isotopic labels in untargeted metabolomics. Anal Chem 86(3):1632–1639PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Oliver SG, Winson MK, Kell DB, Baganz F Systematic functional analysis of the yeast genome. Trends Biotechnol 16(9):373–378Google Scholar
  60. 60.
    Frisvad JC, Filtenborg O (1983) Classification of terverticillate penicillia based on profiles of mycotoxins and other secondary metabolites. Appl Environ Microbiol 46(6):1301–1310PubMedCentralPubMedGoogle Scholar
  61. 61.
    Frisvad JC, Andersen B, Thrane U (2008) The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi. Mycol Res 112(2):231–240PubMedCrossRefGoogle Scholar
  62. 62.
    Scott PM, Lawrence JW, van Walbeek W (1970) Detection of mycotoxins by thin-layer chromatography: application to screening of fungal extracts. Appl microbiol 20(5):839–842PubMedCentralPubMedGoogle Scholar
  63. 63.
    Kang D, Kim J, Choi JN, Liu KH, Lee CH (2011) Chemotaxonomy of Trichoderma spp. using mass spectrometry-based metabolite profiling. J Microbiol Biotechnol 21(1):5–13PubMedCrossRefGoogle Scholar
  64. 64.
    Aliferis K, Cubeta M, Jabaji S (2013) Chemotaxonomy of fungi in the Rhizoctonia solani species complex performing GC/MS metabolite profiling. Metabolomics 9(1):159–169CrossRefGoogle Scholar
  65. 65.
    Nielsen KF, Smedsgaard J (2003) Fungal metabolite screening: database of 474 mycotoxins and fungal metabolites for dereplication by standardised liquid chromatography–UV–mass spectrometry methodology. J Chromatogr A 1002(1–2):111–136PubMedCrossRefGoogle Scholar
  66. 66.
    Stadler M, Ju Y-M, Rogers JD (2004) Chemotaxonomy of Entonaema, Rhopalostroma and other Xylariaceae. Mycol Res 108(03):239–256PubMedCrossRefGoogle Scholar
  67. 67.
    Abreu LM, Costa SS, Pfenning LH, Takahashi JA, Larsen TO, Andersen B (2012) Chemical and molecular characterization of Phomopsis and Cytospora-like endophytes from different host plants in Brazil. Fungal Biol 116(2):249–260PubMedCrossRefGoogle Scholar
  68. 68.
    Deane C, Mitchell D (2014) Lessons learned from the transformation of natural product discovery to a genome-driven endeavor. J Ind Microbiol Biotechnol 41(2):315–331PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Bode HB, Bethe B, Höfs R, Zeeck A (2002) Big effects from small changes: possible ways to explore nature’s chemical diversity. Chembiochem 3(7):619–627PubMedCrossRefGoogle Scholar
  70. 70.
    Gross H (2007) Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. Appl Microbiol Biotechnol 75(2):267–277PubMedCrossRefGoogle Scholar
  71. 71.
    Lim FY, Sanchez JF, Wang CCC, Keller NP (2012) Toward awakening cryptic secondary metabolite gene clusters in filamentous fungi. In: David AH (ed). Methods in enzymology, vol 517. Elsevier, Amsterdam, pp 303–324Google Scholar
  72. 72.
    Williams RB, Henrikson JC, Hoover AR, Lee AE, Cichewicz RH (2008) Epigenetic remodeling of the fungal secondary metabolome. Org Biomol Chem 6(11):1895–1897PubMedCrossRefGoogle Scholar
  73. 73.
    Brakhage AA, Schroeckh V (2011) Fungal secondary metabolites—strategies to activate silent gene clusters. Fungal Genet Biol 48(1):15–22PubMedCrossRefGoogle Scholar
  74. 74.
    Elias BC, Said S, de Albuquerque S, Pupo MT (2006) The influence of culture conditions on the biosynthesis of secondary metabolites by Penicillium verrucosum Dierck. Microbiol Res 161(3):273–280PubMedCrossRefGoogle Scholar
  75. 75.
    Sørensen JL, Sondergaard TE (2014) The effects of different yeast extracts on secondary metabolite production in Fusarium. Int J Food Microbiol 170(0):55–60PubMedCrossRefGoogle Scholar
  76. 76.
    Scherlach K, Hertweck C (2009) Triggering cryptic natural product biosynthesis in microorganisms. Org Biomol Chem 7(9):1753–1760PubMedCrossRefGoogle Scholar
  77. 77.
    Wiemann P, Sieber CMK, von Bargen KW, Studt L, Niehaus E-M, Espino JJ et al (2013) Deciphering the cryptic genome: genome-wide analyses of the rice pathogen Fusarium fujikuroi reveal complex regulation of secondary metabolism and novel metabolites. PLoS Pathog 9(6):e1003475PubMedCentralPubMedCrossRefGoogle Scholar
  78. 78.
    Connolly LR, Smith KM, Freitag M (2013) The Fusarium graminearum Histone H3 K27 Methyltransferase KMT6 regulates development and expression of secondary metabolite gene clusters. PLoS Genet 9(10):e1003916PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Lang G, Mayhudin NA, Mitova MI, Sun L, van der Sar S, Blunt JW et al (2008) Evolving trends in the dereplication of natural product extracts: new methodology for rapid, small-scale investigation of natural product extracts. J Nat Prod 71(9):1595–1599PubMedCrossRefGoogle Scholar
  80. 80.
    Forner D, Berrué F, Correa H, Duncan K, Kerr RG (2013) Chemical dereplication of marine actinomycetes by liquid chromatography–high resolution mass spectrometry profiling and statistical analysis. Anal Chim Acta 805(0):70–79PubMedCrossRefGoogle Scholar
  81. 81.
    Kildgaard S, Mansson M, Dosen I, Klitgaard A, Frisvad JC, Larsen TO et al (2014) Accurate dereplication of bioactive secondary metabolites from marine-derived fungi by UHPLC-DAD-QTOFMS and a MS/HRMS library. Mar Drugs 12(6):3681–3705PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    Breitling R, Ceniceros A, Jankevics A, Takano E (2013) Metabolomics for secondary metabolite research. Metabolites 3(4):1076–1083PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Allwood JW, Heald J, Lloyd A, Goodacre R, Mur LJ (2012) Separating the Inseparable: The metabolomic analysis of plant–pathogen interactions. In: Hardy NW, Hall RD (eds). Plant metabolomics—methods in molecular biology, vol. 860. Humana Press, New York, pp 31–49Google Scholar
  84. 84.
    Aliferis KA, Jabaji S (2012) Deciphering plant–pathogen interactions applying metabolomics: principles and applications. Can J Plant Pathol 34(1):29–33CrossRefGoogle Scholar
  85. 85.
    Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY, Kersten RD et al (2012) Mass spectral molecular networking of living microbial colonies. PNAS 1743–1752Google Scholar
  86. 86.
    Jonkers W, Rodriguez Estrada AE, Lee K, Breakspear A, May G, Kistler HC (2012) Metabolome and Transcriptome of the Interaction between Ustilago maydis and Fusarium verticillioides in vitro. Appl Environ Microbiol 78(10):3656–3667PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Balmer D, de Papajewski DV, Planchamp C, Glauser G, Mauch-Mani B (2013) Induced resistance in maize is based on organ-specific defence responses. Plant J 74(2):213–225PubMedCrossRefGoogle Scholar
  88. 88.
    Brotman Y, Lisec J, Méret M, Chet I, Willmitzer L, Viterbo A (2012) Transcript and metabolite analysis of the Trichoderma-induced systemic resistance response to Pseudomonas syringae in Arabidopsis thaliana. Microbiology 158(1):139–146PubMedCrossRefGoogle Scholar
  89. 89.
    Vincent D, Du Fall LA, Livk A, Mathesius U, Lipscombe RJ, Oliver RP et al (2012) A functional genomics approach to dissect the mode of action of the Stagonospora nodorum effector protein SnToxA in wheat. Mol Plant Pathol 13(5):467–482PubMedCrossRefGoogle Scholar
  90. 90.
    Warth B, Parich A, Bueschl C, Schoefbeck D, Neumann NKN, Kluger B et al (2014) GC–MS based targeted metabolic profiling identifies changes in the wheat metabolome following deoxynivalenol treatment. Metabolomics (in press). doi. 10.1007/s11306-014-0731-1Google Scholar
  91. 91.
    Voll LM, Horst RJ, Voitsik AM, Zajic D, Samans B, Pons-Kühnemann J et al (2011) Common motifs in the response of cereal primary metabolism to fungal pathogens are not based on similar transcriptional reprogramming. Front Plant Sci 2:39PubMedCentralPubMedCrossRefGoogle Scholar
  92. 92.
    Allwood JW, Clarke A, Goodacre R, Mur LAJ (2010) Dual metabolomics: a novel approach to understanding plant–pathogen interactions. Phytochemistry 71(5–6):590–597PubMedCrossRefGoogle Scholar
  93. 93.
    Cuomo CA, Güldener U, Xu J-R, Trail F, Turgeon BG, Di Pietro A et al (2007) The Fusarium graminearum genome reveals a link between localized polymorphism and pathogen specialization. Science 317(5843):1400–1402PubMedCrossRefGoogle Scholar
  94. 94.
    Kubicek C, Herrera-Estrella A, Seidl-Seiboth V, Martinez D, Druzhinina I, Thon M et al (2011) Comparative genome sequence analysis underscores mycoparasitism as the ancestral life style of Trichoderma. Genome Biol 12(4):R40PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Crutcher FK, Parich A, Schuhmacher R, Mukherjee PK, Zeilinger S, Kenerley CM (2013) A putative terpene cyclase, vir4, is responsible for the biosynthesis of volatile terpene compounds in the biocontrol fungus Trichoderma virens. Fungal Genet Biol 56(0):67–77PubMedCrossRefGoogle Scholar
  96. 96.
    Roze L, Chanda A, Laivenieks M, Beaudry R, Artymovich K, Koptina A et al (2010) Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism. BMC Biochem 11(1):33PubMedCentralPubMedCrossRefGoogle Scholar
  97. 97.
    Roze L, Chanda A, Linz JE (Jan 2011) Compartmentalization and molecular traffic in secondary metabolism: a new understanding of established cellular processes. Fungal Genet Biol 48(1):35–48PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Bueschl C, Krska R, Kluger B, Schuhmacher R (2013) Isotopic labeling-assisted metabolomics using LC–MS. Anal Bioanal Chem 405(1):27–33PubMedCentralPubMedCrossRefGoogle Scholar
  99. 99.
    Chokkathukalam A, Kim D-H, Barrett MP, Breitling R, Creek DJ (2014) Stable isotope-labeling studies in metabolomics: new insights into structure and dynamics of metabolic networks. Bioanalysis 6(4):511–524PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Cano PM, Jamin EL, Tadrist S, Bourdaud’hui P, Péan M, Debrauwer L et al (2013) New untargeted metabolic profiling combining mass spectrometry and isotopic labeling: application on Aspergillus fumigatus grown on wheat. Anal Chem 85(17):8412–8420PubMedCrossRefGoogle Scholar
  101. 101.
    Kluger B, Bueschl C, Lemmens M, Berthiller F, Häubl G, Jaunecker G et al (2012) Stable isotopic labelling-assisted untargeted metabolic profiling reveals novel conjugates of the mycotoxin deoxynivalenol in wheat. Anal Bioanal Chem 5031–5036Google Scholar
  102. 102.
    Hsu C-C, ElNaggar MS, Peng Y, Fang J, Sanchez LM, Mascuch SJ et al (2013) Real-time metabolomics on living microorganisms using ambient electrospray ionization flow-probe. Anal Chem 85(15):7014–7018PubMedCentralPubMedCrossRefGoogle Scholar
  103. 103.
    Hu J-B, Chen Y-C, Urban PL (2012) On-target labeling of intracellular metabolites combined with chemical mapping of individual hyphae revealing cytoplasmic relocation of isotopologues. Anal Chem 84(11):5110–5116PubMedCrossRefGoogle Scholar
  104. 104.
    Moree W, Yang J, Zhao X, Liu W-T, Aparicio M, Atencio L et al (2013) Imaging mass spectrometry of a coral microbe interaction with fungi. J Chem Ecol 39(7):1045–1054Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Bernhard Kluger
    • 1
    Email author
  • Sylvia Lehner
    • 1
  • Rainer Schuhmacher
    • 1
  1. 1.Department of Agrobiotechnology (IFA-Tulln), Center for Analytical ChemistryUniversity of Natural Resources and Life SciencesTullnAustria

Personalised recommendations