Applied Microbiology and Biotechnology

, Volume 82, Issue 3, pp 579–586 | Cite as

Potential natural product discovery from microbes through a diversity-guided computational framework

  • Eakasit Pacharawongsakda
  • Sunai Yokwai
  • Supawadee IngsriswangEmail author


As the occurrence of natural compounds is related to the spatial distribution and evolution of microorganisms for biological and ecological relevance, the data integration of chemistry, geography, and phylogeny within an analytical framework is needed to make better decisions on sourcing the microbes for drug discovery. Such a framework should help researcher to decide on (a) which microorganisms are capable to produce the structurally diverse-bioactive compounds and (b) where those microbes could be found. Here, we present GIST (Geospatial Integrated Species, sites and bioactive compound relationships Tracking tool), a computational framework that could describe and compare how the chemical and genetic diversity varied among microbes in different areas. GIST mainly exploits the measures of bioactive diversity (BD) and phylogenetic diversity (PD), derived from the branch length of bioactive dendrogram and phylogenetic tree, respectively. Based on BD and PD, our framework could provide guidance and tools for measuring, monitoring, and evaluating of patterns and changes in biodiversity of microorganisms to improve the success rate of drug discovery.


Bioactive diversity Phylogenetic diversity Microbial collection Natural products Dendrogram Drug discovery 



We are grateful to the National Center for Genetic Engineering and Biotechnology for funding part of this work. The authors wish to thank Dr. Duangdao Wichadakul, Dr. Darin Kongkasuriyachai, and Dr. Nitsara Karoonuthaisiri for critically reading the manuscript.

Supplementary material

253_2008_1847_MOESM1_ESM.doc (100 kb)
ESM 1 (DOC 99.5 kb)


  1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSIBLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402 doi: 10.1093/nar/25.17.3389 CrossRefGoogle Scholar
  2. Anderson RP, Lew D, Peterson AT (2003) Evaluating predictive models of species' distributions: criteria for selecting optimal models. Ecol Model 162:211–232 doi: 10.1016/S0304-3800(02)00349-6 CrossRefGoogle Scholar
  3. Becker SA, Palsson BØ (2005) Genome-scale reconstruction of the metabolic network in Staphylococcus aureus N315: an initial draft to the two-dimensional annotation. BMC Microbiol 5. doi: 10.1186/1471-2180-5-8
  4. Bergmann S, Schümann J, Scherlach K, Lange C, Brakhage AA, Hertweck C (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3:213–217 doi: 10.1038/nchembio869 CrossRefGoogle Scholar
  5. Bok J, Hoffmeister D, Maggio-Hall L, Murillo R, Glasner J, Keller N (2006) Genome mining for Aspergillus natural products. Chem Biol 13:31–37 doi: 10.1016/j.chembiol.2005.10.008 CrossRefGoogle Scholar
  6. Challis GL (2008) Genome mining for novel natural product discovery. J Med Chem 51:2618–2628 doi: 10.1021/jm700948z CrossRefGoogle Scholar
  7. Challis GL, Ravel J (2000) Coelichelin, a new peptide siderophore encoded by the Streptomyces coelicolor genome: structure prediction from the sequence of its non-ribosomal peptide synthetase. FEMS Microbiol Lett 187:111–114 doi: 10.1111/j.1574-6968.2000.tb09145.x CrossRefGoogle Scholar
  8. Coley PD, Heller MV, Aizprua R, Araúz B, Flores N, Correa M, Gupta M, Solis PN, Ortega-Barría E, Romero LI, Gómez B, Ramos M, Cubilla-Rios L, Capson TL, Kursar TA (2003) Using ecological criteria to design plant collection strategies for drug discovery. Front Ecol Environ 1:421–428 doi: 10.1890/1540-9295(2003)001[0421:UECTDP]2.0.CO;2 CrossRefGoogle Scholar
  9. Cressie NAC (1993) Statistics for Spatial Data, revised Ed. Wiley, New YorkGoogle Scholar
  10. Czárán TL, Hoekstra RF, Pagie L (2002) Chemical warfare between microbes promotes biodiversity. Proc Natl Acad Sci (PNAS) 99:786–790 doi: 10.1073/pnas.012399899 CrossRefGoogle Scholar
  11. Faith DP (1992) Conservation evaluation and phylogenetic diversity. Biol Cons 61:1–10 doi: 10.1016/0006-3207(92)91201-3 CrossRefGoogle Scholar
  12. Felsenstein J (1989) PHYLIP—Phylogeny Inference Package (Version 3.2). Cladistics 5:164–166Google Scholar
  13. Fenical W, Jensen PR (2006) Developing a new resource for drug discovery: marine actinomycete bacteria. Nat Chem Biol 2:666–673 doi: 10.1038/nchembio841 CrossRefGoogle Scholar
  14. Francke C, Siezen RJ, Teusink B (2005) Reconstructing the metabolic network of a bacterium from its genome. Trends Microbiol 13:550–558 doi: 10.1016/j.tim.2005.09.001 CrossRefGoogle Scholar
  15. Herrgård MJ, Swainston N, Dobson P, Dunn WB, Arga KY, Arvas M, Blüthgen N, Borger S, Costenoble R, Heinemann M, Hucka M, Novère NL, Li P, Liebermeister W, Mo ML, Oliveira AP, Petranovic D, Pettifer S, Simeonidis E, Smallbone K, Spasic I, Weichart D, Brent R, Broomhead DS, Westerhoff HV, Kürdar B, Penttilä M, Klipp E, Palsson BØ, Sauer U, Oliver SG, Mendes P, Nielsen J, Kell DB (2008) A consensus yeast metabolic network reconstruction obtained from a community approach to systems biology. Nat Biotechnol 26:1155–1160 doi: 10.1038/nbt1492 CrossRefGoogle Scholar
  16. Inglis GD, Goettel MS, Butt TM, Strasser H (2001) Use of hyphomycetous fungi for managing insect pests. Fungi as biocontrol agents progress, problems and potential. CABI, UKGoogle Scholar
  17. Ingsriswang S, Pacharawongsakda E (2007) sMOL Explorer: an open source, web enabled database and exploration tool for Small MOLecules datasets. Bioinformatics 23:2498–2500 doi: 10.1093/bioinformatics/btm363 CrossRefGoogle Scholar
  18. Isaka M, Punya J, Lertwerawat Y, Tanticharoen M, Thebtaranonth Y (1999) Antimalarial activity of macrocyclic trichothecenes isolated from the fungus Myrothecium verrucaria. J Nat Prod 62:329–331 doi: 10.1021/np980323x CrossRefGoogle Scholar
  19. Isaka M, Srisanoh U, Lartpornmatulee N, Boonruangprapa T (2007) ES-242 derivatives and cycloheptapeptides from Cordyceps sp. strains BCC 16173 and BCC 16176. J Nat Prod 70:1601–1604 doi: 10.1021/np070357h CrossRefGoogle Scholar
  20. Jordan GE, Piel WH (2008) PhyloWidget: web-based visualizations for the tree of life. Bioinformatics 24:1641–1642 doi: 10.1093/bioinformatics/btn235 CrossRefGoogle Scholar
  21. Kim TY, Hewavitharana AK, Shaw PN, Fuerst JA (2006) Discovery of a new source of rifamycin antibiotics in marine sponge Actinobacteria by phylogenetic prediction. Appl Environ Microbiol 72:2118–2125 doi: 10.1128/AEM.72.3.2118-2125.2006 CrossRefGoogle Scholar
  22. Knight V, Sanglier JJ, DiTullio D, Braccili S, Bonner P, Waters J, Hughesand D, Zhang L (2003) Diversifying microbial natural products for drug discovery. Appl Microbiol Biotechnol 62:446–458 doi: 10.1007/s00253-003-1381-9 CrossRefGoogle Scholar
  23. Krause S, Willighagen E, Steinbeck C (2000) JChemPaint—using the collaborative forces of the internet to develop a free editor for 2D chemical structures. Molecules 5:93–98CrossRefGoogle Scholar
  24. Lam KS (2007) New aspects of natural products in drug discovery. Trends Microbiol 15:279–289 doi: 10.1016/j.tim.2007.04.001 CrossRefGoogle Scholar
  25. Nix HA (1986) A biogeographic analysis of Australian elapid snakes. In: R. Longmore (Ed.) Atlas of Elapid Snakes of Australia. Australian Flora and Fauna Series Number 7, Australian Government Publishing Service, Canberra.Google Scholar
  26. Pebesma EJ (2004) Multivariable geostatistics in S: the gstat package. Comput Geosci 30:683–691CrossRefGoogle Scholar
  27. Petchey OL, Gaston KJ (2002) Functional diversity (FD), species richness and community composition. Ecol Lett 5:402–411 doi: 10.1046/j.1461-0248.2002.00339.x CrossRefGoogle Scholar
  28. R Development Core Team (2008) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, AustriaGoogle Scholar
  29. Rønsted N, Savolainen V, Mølgaard P, Jäger AK (2008) Phylogenetic selection of Narcissus species for drug discovery. Biochem Syst Ecol 36:417–422 doi: 10.1016/j.bse.2007.12.010 Google Scholar
  30. Ruanglek V, Chokpaiboon S, Rattanaphan N, Madla S, Auncharoen P, Bunyapaiboonsri T, Isaka M (2007) Menisporopsin B, a new polyester from the seed fungus Menisporopsis theobromae BCC 4162. J Antibiot (Tokyo) 60:748–751Google Scholar
  31. Santana FS, Fonseca RR, Saraiva AM, Corrêa PLP, Bravo C, Giovanni R (2006) openModeller an open framework for ecological niche modeling: analysis and future improvements. World Conference on Computers in Agriculture and Natural ResourcesGoogle Scholar
  32. Sirimungkararat S, Wongkaeo A, Hywel-Jones N, Saksirirat W (2002) New species of entomopathogenic fungi in Thailand. Proceedings of KKU annual agricultural seminar for year 2002, 231–245Google Scholar
  33. Steinbeck C, Han Y, Kuhn S, Horlacher O, Luttmann E, Willighagen E (2006) Recent developments of the chemistry development kit (CDK)—an open-source Java library for chemo- and bioinformatics. Curr Pharm Des 12:2111–20 doi: 10.1021/ci025584y CrossRefGoogle Scholar
  34. Thompson JD, Higgins DG, Gibson TJ (1994) Clustal W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680CrossRefGoogle Scholar
  35. Vongvanich N, Kittakoop P, Isaka M, Trakulnaleamsai S, Vimuttipong S, Tanticharoen M, Thebtaranonth Y (2002) Hirsutellide A, a new antimycobacterial cyclohexadepsipeptide from the entomopathogenic fungus Hirsutella kobayasii. J Nat Prod 65:1346–1348 doi: 10.1021/np020055+ CrossRefGoogle Scholar
  36. Webb CO, Ackerly DD, Kembel SW (2008) Phylocom: software for the analysis of phylogenetic community structure and trait evolution. Bioinformatics 24:2098–2100 doi: 10.1093/bioinformatics/btn358 CrossRefGoogle Scholar
  37. Witten IH, Frank E (2005) Data mining: practical machine learning tools and techniques. Morgan Kaufmann, San FranciscoGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Eakasit Pacharawongsakda
    • 1
  • Sunai Yokwai
    • 1
  • Supawadee Ingsriswang
    • 1
    Email author
  1. 1.Information Systems Laboratory, Bioresource Technology UnitNational Center for Genetic Engineering and BiotechnologyPathumthaniThailand

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