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Chapter 6 : Metabolomics for the Discovery of Novel Compounds

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Abstract:

Exometabolomics is a more restricted discipline, only concerned with detection of all secreted or cell wall-deposited secondary metabolites. This chapter outlines the procedures for optimal discovery of new compounds, based on experience with filamentous fungi. Sequencing of ribosomal genes is often used for identification in bacteriology and mycology, but experience within the fungi has shown that sequencing one or two housekeeping genes gives a much more accurate identification at the species level than ribosomal genes alone. Ultrasonication helps in extracting a large proportion of the secondary metabolites present in the agar plugs. This mixture is especially well suited for apolar and medium polar compounds. Usually the extraction mixture is then evaporated and the remaining dry extract redissolved in methanol. By use of the 3:2:1 mixture many “primary metabolites” are not included in the final extract being analyzed. New metabolites from a new species in that group would then probably be a terpene or a nonribosomal peptide, even though a fifth kind of polyketide could also be the bioactive compound. One of the most important parts of finding new compounds is to be able to quickly deselect already known compounds. The use of fast methods such a direct-inlet MS combined with databases is one possibility, while UPLC-UV-MS may also prove to be the chosen chemical screening technique for new bioactive natural products in the future.

Citation: Frisvad J. 2010. Metabolomics for the Discovery of Novel Compounds, p 73-77. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch6

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High-Performance Liquid Chromatography
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Aspergillus niger
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1. Alberto, F.,, D. Navarro,, R. P. de Vries,, M. Asther, and, E. Record. 2009. Technical advances in fungal biotechnology: development of a miniaturized culture method and an automated high-throughput screening. Lett. Appl. Microbiol. 49:278282.
2. Andersen, B.,, A. Dongo, and, P. M. Pryor. 2008. Secondary metabolite profiling of Alternaria dauci, A. porri, A. solani and A. tomatophila. Mycol. Res. 112:241250.
3. Andersen, B.,, M. E. Hansen, and, J. Smedsgaard. 2005. Automated and unbiased classification of chemical profiles from fungi using high performance liquid chromatography. J. Microbiol. Methods 61:295304.
4. Challis, G. L. 2008. Genome mining for novel natural product discovery. J. Med. Chem. 51:26182628.
5. Challis, G. L. and, D. A. Hopwood. 2003. Synergy and contingency as driving forces of the evolution of secondary metabolite production by Streptomyces species. Proc. Natl. Acad. Sci. USA 100:1455514561.
6. Dalsgaard, P. W.,, K. F. Nielsen, and, T. O. Larsen. 2005. UV-guided isolation of fungal metabolites by HSCCC. J. Liq. Chromatogr. Relat. Technol. 28:20292039.
7. Denery, J. R.,, M. J. Cooney, and, Q. X. Li, 2006. Metabolic profiling to reflect gene expression in Streptomyces tenjimariensis. Ind. Biotechnol. 2:5154.
8. de Vita-Marques, A. M.,, S. P. Lira,, R. G. S. Berrlinck,, M. H. R. Seleghim,, S. R. P. Sponchiado,, S. M. Tauk-Tornisielo,, M. Barata,, C. Pessoa,, M. O. de Moraes,, B. C. Cavalcanti,, G. G. F. Naschimento,, A. O. de Souza,, F. C. S. Galetti,, C. L. Silva,, M. Silva,, E. F. Pimenta,, O. Thiermann,, M. R. Z. Passarini, and, L. D. Sette. 2008. A multi-screening approach for marine-derived fungal metabolites and the isolation of cyclodepsipeptides from Beauveria feline. Quim. Nova 31:10991103.
9. Fiedler, H.-P.,, C. Bruntner,, A. Bull,, A. Ward,, M. Goodfellow,, O. Potterat,, C. Puder, and, G. Mihm. 2005. Marine actinomycetes as a source of novel secondary metabolites. Antonie van Leeuwenhoek 87:3742.
10. Filtenborg, O., and, J. C. Frisvad. 1980. A simple screening method for toxigenic fungi in pure cultures. Lebensm.-Wiss. Technol. 13:128130.
11. Filtenborg, O.,, J. C. Frisvad, and, J. A. Svendsen. 1983. Simple screening method for moulds producing intracel-lular mycotoxins in pure cultures. Appl. Environ. Microbiol. 45:581585.
12. Fisch, K. M.,, A. F. Gillaspy,, M. Gipson,, J. C. Henrikson,, A. R. Hoover,, L. Jackson,, F. Z. Najar,, H. Wägele, and, R. H. Cichewicz. 2009. Chemical induction of silent bio-synthetic pathway transcription in Aspergillus niger. J. Ind. Microbiol. Biotechnol. 36:11991213.
13. Frisvad, J. C.,, B. Andersen, and, U. Thrane. 2008. The use of secondary metabolite profiling in fungal taxonomy. Mycol. Res. 112:231240.
14. Frisvad, J. C., and, O. Filtenborg. 1983. Classification of terverticillate Penicillia based on profiles of mycotoxins and other secondary metabolites. Appl. Environ. Microbiol. 46:13011310.
15. Frisvad, J. C.,, J. M. Franks,, J. A. M. P. Houbraken,, A. F. A. Kuijpers, and, R. A. Samson. 2004. New ochra-toxin producing species of Aspergillus section Circumdati. Stud. Mycol. 50:2343.
16. Frisvad, J. C.,, T. O. Larsen,, R. de Vries,, M. Meijer,, J. Houbraken,, F. J. Cabañes,, K. Ehrlich, and, R. A. Samson. 2007. Secondary metabolite profiling, growth profiles and other tools for species recognition and important Aspergillus mycotoxins. Stud. Mycol. 59:3137.
17. Frisvad, J.-C.,, C. Rank,, K. F. Nielsen, and, T. O. Larsen. 2009. Metabolomics of Aspergillus fumigatus. Med. Mycol. 47:S53S71.
18. Frisvad, J. C.,, J. Smedsgaard,, T. O. Larsen, and, R. A. Samson. 2004. Mycotoxins, drugs and other extrolites produced by species in Penicillium subgenus Penicillium. Stud. Mycol. 49:201241.
19. Frisvad, J. C., and, U. Thrane. 1987. Standardized high-performance liquid chromatography of 182 mycotoxins and other fungal metabolites based on alkylphenone indices and UV-VIS spectra (diode-array detection). J. Chromatogr. 404:195214.
20. Frisvad, J. C., and, U. Thrane. 1993. Liquid column chromatography of mycotoxins, p. 253372. In V. Betina (ed.), Chromatography of Mycotoxins: Techniques and Applications. Journal of Chromatography Library, 54. Elsevier, Amsterdam, The Netherlands.
21. Frisvad, J. C.,, U. Thrane, and, O. Filtenborg. 1998. Role and use of secondary metabolites in fungal taxonomy, p. 289319. In J. C. Frisvad,, P. D. Bridge, and, D. K. Arora (ed.), Chemical Fungal Taxonomy. Marcel Dekker, New York, NY.
22. Geng, R.,, X. Meng,, G. Bai, and, G. Luo. 2008. Profiling of acarviostatin family secondary metabolites secreted by Streptomyces coelicoflavus ZG0656 using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Anal. Chem. 80:75547561.
23. Gross, H. 2009. Genomic mining, a concept for the discovery of new bioactive natural products. Curr. Opin. Drug Discov. Dev. 12:207219.
24. Hansen, M. E., and, J. Smedsgaard. 2006. A new matching algorithm for high resolution mass spectra. J. Am. Soc. Mass Spectrom. 15:11731180.
25. Hansen, M. E.,, J. Smedsgaard, and, T. O. Larsen. 2005. X-hitting: an algorithm for novelty detection and derep-lication by UV-spectra in complex mixtures of natural products. Anal. Chem. 77:68056817.
26. Houbraken, J.,, M. Due,, J. Varga,, M. Meijer,, J. C. Frisvad, and, R. A. Samson. 2007. Polyphasic taxonomy of Aspergillus section Usti. Stud. Mycol. 59:107128.
27. Isaka, M.,, N. L. Hywel-Jones,, M. Sappan,, S. Mongkolsamrit, and, S. Saidaengkham. 2009. Hopane triterpenes as chemotaxonomic markers for the insect pathogens Hypocrella s. lat. and Aschersonia. Mycol. Res. 113:491497.
28. Jensen, P. R.,, P. G. Williams,, D. C. Oh,, L. Zeigler, and, W. Fenical. 2007. Species-specific secondary metabolite production in marine actinomycetes of the genus Salinispora. Appl. Environ. Microbiol. 73:11461152.
29. Larsen, T. O., and, J. C. Frisvad. 1995. Comparison of different methods for collection of volatile chemical markers from fungi. J. Microbiol. Methods 24:135144.
30. Larsen, T. O.,, B. O. Petersen,, D. Sørensen,, J. Ø. Duus,, J. C. Frisvad, and, M. E. Edberg. 2005. Discovery of new natural products by application of X-hitting, a novel algorithm for automated comparison of full UV-spectra, combined with structural determination by NMR spectros-copy. J. Nat. Prod. 68:871874.
31. Larsen, T. O.,, J. Smedsgaard,, K. F. Nielsen,, M. E. Hansen, and, J. C. Frisvad. 2005. Phenotypic taxonomy and metabolite profiling in microbial drug discovery. Nat. Prod. Rep. 22:672695.
32. Meinwald, J. 2009. The chemistry of biotic interactions in perspective: small molecules take center stage. J. Org. Chem. 74:18131825.
33. Molinski, T. F. 2009. Nanomole-scale natural products discovery. Curr. Opin. Drug Discov. Dev. 12:197206.
34. Nielsen, K. F.,, J. M. Mogensen,, M. Johansen,, T. O. Larsen, and, J. C. Frisvad. 2009. Review of secondary metabolites and mycotoxins from the Aspergillus niger group. Anal. Bioanal. Chem. doi: 10.1007/s00216–009-3081–5.
35. Nielsen, K. F., and, J. Smedsgaard. 2003. Fungal metabolite screening: database of 474 mycotoxins and fungal metabolites for dereplication by standard liquid chromatography-UV-mass spectrometry methodology. J. Chromatogr. A 1002:111136.
36. Nielsen, K. F.,, J. Smedsgaard,, T. O. Larsen,, F. Lund,, U. Thrane, and, J. C. Frisvad. 2004. Chemical identification of fungi—metabolite profiling and metabolomics, p. 1935. In D. K. Arora (ed.), Fungal Biotechnology in Agricultural, Food and Environmental Applications. Marcel Dekker, New York, NY.
37. Nielsen, M. S.,, P. V. Nielsen, and, J. C. Frisvad. 1996. Micellar electrokinetic capillary chromatography of fungal metabolites: resolution optimized by experimental design. J. Chromatogr. A 721:337344.
38. Nielsen, N.-P. V.,, J. Smedsgaard, and, J. C. Frisvad. 1999. Full second-order chromatographic/spectrometric data matrices for automated sample identification and component analysis by non data reducing image analysis. Anal. Chem. 71:727735.
39. Pope, G. A.,, D. A. MacKenzie,, M. Defernez, and, I. N. Roberts. 2009. Metabolic footprinting for the study of microbial diversity. Cold Spring Harbor Protoc. doi: 10.1101/pdb.prot5222.
40. Samson, R. A.,, S. Hong,, S. W. Peterson,, J. C. Frisvad, and, J. Varga. 2007. Diagnostic tools to identify black aspergilli. Stud. Mycol. 59:129145.
41. Samson, R. A.,, S. Hong,, S. W. Peterson,, J. C. Frisvad, and, J. Varga. 2007. Polyphasic taxonomy of Aspergillus section Fumigati and its teleomorph Neosartorya. Stud. Mycol. 59:147207.
42. Samson, R. A.,, K. A. Seifert,, A. F. A. Kuijpers,, J. A. M. P. Houbraken, and, J. C. Frisvad. 2004. Phylogenetic analysis of Penicillium subgenus Penicillium using partial β tubulin sequences. Stud. Mycol. 49:175200.
43. Schroeder, F. C., and, M. Gronquist. 2006. Extending the scope of NMR spectroscopy with microcoil probes. Angew. Chem. Int. Ed. 45:71227133.
44. Schroeder, F. C.,, D. M. Gibson,, A. C. L. Churchill,, P. Sojikul,, E. J. Wursthorn,, S. B. Krasnoff, and, J. Clardy. 2007. Differential analysis of 2D NMR spectra: new natural products from a pilot-scale fungal extract library. Angew. Chem. Int. Ed. 46:901904.
45. Schulz, B.,, S. Draeger,, T. E. de la Cruz,, J. Rheinheimer,, K. Siems,, S. Loesgen,, J. Bitzer,, O. Schloerke,, A. Zeeck,, I. Kock,, H. Hussain,, J. Q. Dai, and, K. Krohn. 2008. Screening strategies for obtaining novel, biologically active, fungal secondary metabolites from marine habitats. Bot. Mar. 51:219234.
46. Schwab, E. K.,, J. W. Bok,, M. Tribus,, J. Galehr,, S. Grassle, and, N. P. Keller. 2007. Histone deacetylase activity regulates chemical diversity in Aspergillus. Eu-karyot. Cell 6:16561664.
47. Skouboe, P.,, J. C. Frisvad,, D. Lauritsen,, M. Boysen,, J. W. Taylor, and, L. Rossen. 1999. Nucleotide sequences from the ITS region of Penicillium species. Mycol. Res. 103:873881.
48. Smedsgaard, J. 1997. Micro-scale extraction procedure for standardized screening of fungal metabolite production in cultures. J. Chromatogr. A 760:264270.
49. Smedsgaard, J., and, J. C. Frisvad. 1996. Using direct electrospray mass spectrometry in taxonomy and secondary metabolite profiling of crude fungal extracts. J. Microbiol. Methods 25:517.
50. Smedsgaard, J.,, M. E. Hansen, and, J. C. Frisvad. 2004. Classification of terverticillate Penicillia by electrospray mass spectrometric profiling. Stud. Mycol. 49:243251.
51. Smedsgaard, J., and, J. Nielsen. 2005. Metabolite profiling of fungi and yeast: from phenotype to metabolome by MS and informatics. J. Exp. Bot. 56:273286.
52. Stadler, M.,, H. Wollweber,, A. Mühlbauer,, T. Henkel,, Y. Asahawa,, T. Hashimoto,, Y. M. Ju,, J. D. Rogers,, H. G. Welzstein, and, H. V. Tichy. 2001. Secondary metabolite profiles, genetic fingerprints and taxonomy of Daldinia and allies. Mycotaxon 77:379429.
53. Thomas, R. 2001. A biosynthetic classification of fungal and Streptomyces fused-ring aromatic polyketides. Chem-BioChem 2:612627.
54. Thrane, U. 1993. Fusarium species and their specific profiles of secondary metabolites, p. 199225. In J. Chelkowski (ed.), Fusarium: Mycotoxins, Taxonomy and Pathogenicity. Elsevier, Amsterdam, The Netherlands.
55. Thrane, U.,, B. Andersen,, J. C. Frisvad, and, J. Smedsgaard. 2007. The exo-metabolome of filamentous fungi, p. 235252. In M. Jewitt and, J. Nielsen (ed.), Metabolomics. A Powerful Tool in Systems Biology. Topics in Current Chemistry, 276. Springer, Berlin, Germany.
56. Tormo, J. R., and, J. B. Garcia. 2005. Automated analysis of HPLC profiles of microbial extracts: a new tool for drug discovery and production, p. 3356. In L. Zhang and, A. L. Demain (ed.), Natural Products. Drug Discovery and Therapeutic Medicine. Humana Press, New York, NY.
57. Urbain, A.,, A. Marston,, E. Marsden-Edwards, and, K. Hostettmann. 2008. Ultra-performance liquid chromatography/time-of-flight mass spectrometry as a chemotaxonomic tool for the analysis of Gentianaceae species. Phytochem. Anal. 20:134138.
58. Varga, J.,, M. Due,, J. C. Frisvad, and, R. A. Samson. 2007. Polyphasic taxonomy of Aspergillus section Candidi based on molecular, morphological and physiological data. Stud. Mycol. 59:7588.
59. Varga, J.,, J. C. Frisvad, and, R. A. Samson. 2007. Poly-phasic taxonomy of Aspergillus section Fumigati and its teleomorph Neosartorya. Stud. Mycol. 59:147207.
60. Williams, R. B.,, J. Henrikson,, A. R. Hoover,, A. E. Lee, and, R. H. Cichewicz. 2008. Epigenetic remodeling of fungal secondary metabolism. Org. Biomol. Chem. 6:18951897.
61. Xia, J.,, T. C. Bjorndal,, P. Tang, and, D. S. Wishart. 2008. MetaboMiner—semi-automated identification of metabolites from 2D NMR spectra of complex biofluids. BMC Bioinformatics 9:507.
62. Zhang, L. X.,, K. Z. Yan,, Y. Zhang,, R. Huang,, J. Bian,, C. S. Zheng,, H. X. Sun,, Z. H. Chen,, N. Sun,, R. An,, F. G. Min,, W. B. Zhao,, Y. Zhuo,, J. L. You,, Y. J. Song,, Z. Y. Yu,, Z. H. Liu,, K. Q. Yang,, H. Gao,, H. Q. Dai,, Z. L. Zhang,, J. Wang,, C. Z. Fu,, G. Pei,, J. T. Liu,, S. Zhang,, M. Goodfellow,, Y. Y. Jiang,, J. Kuai,, G. C. Zhou, and, X. P. Chen. 2007. High-throughput synergy screening identifies microbial metabolites as combination agents for the treatment of fungal infections. Proc. Natl. Acad. Sci. USA 104:46064611.

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