Development of an Analysis Program of Type I Polyketide Synthase Gene Clusters Using Homology Search and Profile Hidden Markov Model

  • Published : 2009.02.28

Abstract

MAPSI(Management and Analysis for Polyketide Synthase Type I) has been developed to offer computational analysis methods to detect type I PKS(polyketide synthase) gene clusters in genome sequences. MAPSI provides a genome analysis component, which detects PKS gene clusters by identifying domains in proteins of a genome. MAPSI also contains databases on polyketides and genome annotation data, as well as analytic components such as new PKS assembly and domain analysis. The polyketide data and analysis component are accessible through Web interfaces and are displayed with diverse information. MAPSI, which was developed to aid researchers studying type I polyketides, provides diverse components to access and analyze polyketide information and should become a very powerful computational tool for polyketide research. The system can be extended through further studies of factors related to the biological activities of polyketides.

Keywords

References

  1. Altschul, S. F., W. Gish, W. Miller, E. W. Myers, and D. J. Lipman. 1990. Basic local alignment search tool. J. Mol. Biol. 215: 403-410
  2. Aparicio, J. F., P. Caffrey, A. F. A. Marsden, J. Staunton, and P. F. Leadlay. 1994. Limited proteolysis and active-site studies of the first multienzyme component of the erythromycin-producing polyketide synthase. J. Biol. Chem. 269: 8524-8528
  3. Broadhurst, R. W., D. Nietlispach, M. P. Wheatcroft, P. F. Leadlay, and K. J. Weissman. 2003. The structure of docking domains in modular polyketide synthases. Chem. Biol. 10: 723-731 https://doi.org/10.1016/S1074-5521(03)00156-X
  4. Cheng, Y. Q., G. L. Tang, and B. Shen. 2003. Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis. Proc. Natl. Acad. Sci. U.S.A. 100: 3149-3154 https://doi.org/10.1073/pnas.0537286100
  5. Eddy, S. R. 1999. Profile hidden Markov models. Bioinformatics 14: 755-763 https://doi.org/10.1093/bioinformatics/14.9.755
  6. Floss, H. G. and T. W. Yu. 1999. Lessons from the rifamycin biosynthetic gene cluster. Curr. Opin. Chem. Biol. 3: 592- 597 https://doi.org/10.1016/S1367-5931(99)00014-9
  7. Gaitatzis, N., B. Silakowski, B. Kunze, G. Nordsiek, H. Blöcker, G. Höfle, and R. Müller. 2002. The biosynthesis of the aromatic myxobacterial electron transport inhibitor stigmatellin is directed by a novel type of modular polyketide synthase. J. Biol. Chem. 277: 13082-13090 https://doi.org/10.1074/jbc.M111738200
  8. Ikeda, H., T. Nonomiya, M. Usami, T. Ohta, and S. Omura. 1999. Organization of the biosynthetic gene cluster for the polyketide antihelmintic macrolide avermectin in Streptomyces avermitilis. Proc. Natl. Acad. Sci. U.S.A. 96: 9509-9514 https://doi.org/10.1073/pnas.96.17.9509
  9. Jain, A. K., M. N. Murty, and P. J. Flynn. 1999. Data clustering: A review. ACM Computing Surveys 31: 264-323 https://doi.org/10.1145/331499.331504
  10. Kim, B. S., D. H. Sherman, and K. A. Reynolds. 2004. An efficient method for creation and functional analysis of libraries of hybrid type I polyketide synthases. Protein Eng. Des. Sel. 17: 277-284 https://doi.org/10.1093/protein/gzh032
  11. Long, P. F., C. J. Wilkinson, C. P. Bisang, J. Cortes, N. Dunster, M. Oliynyk, et al. 2002. Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase. Mol. Microbiol. 43: 1215-1225 https://doi.org/10.1046/j.1365-2958.2002.02815.x
  12. Marchler-Bauer, A., A. R. Panchenko, B. A. Shoemaker, P. A. Thiessen, L. Y. Geer, and S. H. Bryant. 2002. CDD: A database of conserved domain alignments with links to domain threedimensional structure. Nucleic Acids Res. 30: 281-283 https://doi.org/10.1093/nar/30.1.281
  13. McDaniel, R., A. Thamchaipenet, C. Gustafsson, H. Fu, M. Betlach, and G. Ashley. 1999. Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel 'unnatural' natural products. Proc. Natl. Acad. Sci. U.S.A. 96: 1846-1851 https://doi.org/10.1073/pnas.96.5.1846
  14. McDaniel, R., C. M. Kao, S. J. Hwang, and C. Khosla. 1997. Engineered intermodular and intramodular polyketide synthase fusions. Chem. Biol. 4: 667-674 https://doi.org/10.1016/S1074-5521(97)90222-2
  15. Moore, B. S. and C. Hertweck. 2002. Biosynthesis and attachmentof novel bacterial polyketide synthase starter units. Nat. Prod.Rep. 19: 70-99 https://doi.org/10.1039/b003939j
  16. O'Hagan, D. 1993. Biosynthesis of fatty acid and polyketide metabolites. Nat. Prod. Rep. 10: 593-624 https://doi.org/10.1039/np9931000593
  17. Omura, S., H. Ikeda, J. Ishikawa, A. Hanamoto, C. Takahashi, M. Shinose, et al. 2001. Genome sequence of an industrial microorganism Streptomyces avermitilis: Deducing the ability of producing secondary metabolites. Proc. Nat. Acad. Sci. U.S.A. 98: 12215-12220 https://doi.org/10.1073/pnas.211433198
  18. Pfeifer, B. A. and C. Khosla. 2001. Biosynthesis of polyketides in heterologous hosts. Microbiol. Mol. Biol. Rev. 65: 106-118 https://doi.org/10.1128/MMBR.65.1.106-118.2001
  19. Rawlings, B. J. 2001. Type I polyketide biosynthesis in bacteria(Part A - erythromycin biosynthesis). Nat. Prod. Rep. 18: 190-227 https://doi.org/10.1039/b009329g
  20. Rawlings, B. J. 2001. Type I polyketide biosynthesis in bacteria(Part B). Nat. Prod. Rep. 18: 231-281 https://doi.org/10.1039/b100191o
  21. Salzberg, S. L., A. L. Delcher, S. Kasif, and O. White. 1998. Microbial gene identification using interpolated Markov models. Nucleic Acids Res. 26: 544-548 https://doi.org/10.1093/nar/26.2.544
  22. Shen, B. and C. R. Hutchinson. 1996. Deciphering the mechanism for the assembly of aromatic polyketides by a bacterial polyketide synthase. Proc. Natl. Acad. Sci. U.S.A. 93: 6600-6604 https://doi.org/10.1073/pnas.93.13.6600
  23. Tae, H., E. B. Kong, and K. Park. 2007. ASMPKS: An analysis system for modular polyketide synthases. BMC Bioinformatics 8: 327 https://doi.org/10.1186/1471-2105-8-327
  24. Watanabe, K., C. C. Wang, C. N. Boddy, D. E. Cane, and C. Khosla. 2003. Understanding substrate specificity of polyketide synthase modules by generating hybrid multimodular synthases. J. Biol. Chem. 278: 42020-42026 https://doi.org/10.1074/jbc.M305339200
  25. Wiesmann, K. E., J. Cortes, M. J. Brown, A. L. Cutter, J. Staunton, and P. F. Leadlay. 1995. Polyketide synthesis in vitro on a modular polyketide synthase. Chem. Biol. 2: 583-589 https://doi.org/10.1016/1074-5521(95)90122-1
  26. Witkowski, A., V. S. Rangan, Z. I. Randhawa, C. M. Amy, and S. Smith. 1991. Structural organization of the multifunctional animal fatty-acid synthase. Eur. J. Biochem. 198: 571-579 https://doi.org/10.1111/j.1432-1033.1991.tb16052.x
  27. Wu, K., L. Chung, W. P. Revill, L. Katz, and C. D. Reeves. 2000. The FK520 gene cluster of Streptomycetes hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units. Gene 251: 81-90 https://doi.org/10.1016/S0378-1119(00)00171-2
  28. Yadav, G., R. S. Gokhale, and D. Mohanty. 2003. SEARCHPKS: A program for detection and analysis of polyketide synthase domains. Nucleic Acids Res. 31: 3654-3658 https://doi.org/10.1093/nar/gkg607
  29. Zdobnov, E. M. and R. Apweiler. 2001. InterProScan - an integration platform for the signature-recognition methods in InterPro. Bioinformatics 17: 847-848 https://doi.org/10.1093/bioinformatics/17.9.847