DOI QR코드

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Computational Approach for Biosynthetic Engineering of Post-PKS Tailoring Enzymes

  • 발행 : 2008.12.31

초록

Compounds of polyketide origin possess a wealth of pharmacological effects, including antibacterial, antifungal, antiparasitic, anticancer and immunosuppressive activities. Many of these compounds and their semisynthetic derivatives are used today in the clinic. Most of the gene clusters encoding commercially important drugs have also been cloned and sequenced and their biosynthetic mechanisms studied in great detail. The area of biosynthetic engineering of the enzymes involved in polyketide biosynthesis has recently advanced and been transferred into the industrial arena. In this work, we introduce a computational system to provide the user with a wealth of information that can be utilized for biosynthetic engineering of enzymes involved in post-PKS tailoring steps. Post-PKS tailoring steps are necessary to add functional groups essential for the biological activity and are therefore important in polyketide biosynthesis.

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참고문헌

  1. Altschul, S.F., Gish, W., Miller, W., Myers, E.W., and Lipman, D.J. (1990). Basic local alignment search tool. J. Mol. Biol. 213, 403-410
  2. Faust, B., Hoffmeister, D., Weitnauer, G., Westrich, L., Haag, S., Schneider, P., Decker, H., Kunzel, E., Rohr, J., and Bechthold, A. (2000). Two new tailoring enzymes, a glycosyltransferase and an oxygenase, involved in biosynthesis of the angucycline antibiotic urdamycin A in Streptomyces fradiae Tu2717. Microbiology 146, 147-154 https://doi.org/10.1099/00221287-146-1-147
  3. Floss, H.G. (2001). Antibiotic biosynthesis: from natural to unnatural compounds. J. Ind. Microbiol. Biotechnol. 27, 183-194 https://doi.org/10.1038/sj.jim.7000069
  4. Hopwood, D.A., and Sherman, D.H. (1990). Molecular genetics of polyketides and its comparison with Fatty acid biosynthesis. Annu. Rev. Genet. 24, 37-66 https://doi.org/10.1146/annurev.ge.24.120190.000345
  5. Kwan, D.H., Sun, Y., Schulz, F., Hong, H., Popovic, B., Sim-stark, J.C., Haydock, S.F., and Leadlay, P.F. (2008). Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases. Chem. Biol. 15, 1231-1240 https://doi.org/10.1016/j.chembiol.2008.09.012
  6. Khosla, C., and Zawada, R.J. (1996). Generation of polyketide libraries via combinatorial biosynthesis. Trends. Biotechnol. 14, 335-341 https://doi.org/10.1016/0167-7799(96)10046-9
  7. Lee, D., Seo, H., Hahn, J., Kong, E., and Park, K. (2007). RISS: rice (Oryza sativa L. ssp. Japonica) genome information service system. Genomics & Informatics 5, 194-195
  8. Mendez, C., and Salas, J.A. (2001). Altering the glycosylation pattern of bioactive compounds. Trends. Biotechnol. 19, 449-56 https://doi.org/10.1016/S0167-7799(01)01765-6
  9. Rix, U., Fischer, C., Remsing, L., and Rohr, J. (2002). Modification of post-PKS tailoring steps through combinatorial biosynthesis. Nat. Prod. Rep. 19, 542-580 https://doi.org/10.1039/b103920m
  10. Staunton, J., and Weissman, K. (2001) Polyketide biosynthesis: a millennium review. Nat. Prod. Rep. 18, 380-416 https://doi.org/10.1039/a909079g
  11. Trefzer, A., Salas, J.A., and Bechthold, A. (1999). Genes and enzymes involved in deoxysugar biosynthesis in bacteria. Nat. Prod. Rep. 16, 283-299 https://doi.org/10.1039/a804431g
  12. Xue, Y., and Sherman, D. H. (2001) Biosynthesis and combinatorial biosynthesis of pikromycin-related macrolides in Streptomyces venezuelas. Metab. Eng. 3, 15-26 https://doi.org/10.1006/mben.2000.0167
  13. Yadav, G., Gokhale, R.S., and Mohanty, D. (2003). Computational Approach for prediction of Domain Organization and Substrate Specificity of Modular Polyketide Synthases. J. Mol. Biol. 328, 335-363 https://doi.org/10.1016/S0022-2836(03)00232-8