Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지

Characterization of Tailoring Genes Involved in the Modification of Geldanamycin Polyketide in Streptomyces hygroscopicus JCM4427

  • Shin, Jin-Chul (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Na, Zhu (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Dong-Ho (Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University) ;
  • Kim, Won-Cheol (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Kyeong (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Shen, Yue-Mao (State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences) ;
  • Paik, Sang-Gi (Chungnam National University) ;
  • Hong, Young-Soo (Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Lee, Jung-Joon (Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Published : 2008.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Geldanamycin and its analogs are important anticancer agents that inhibit the newly targeted heat-shock protein (Hsp) 90, which is a chaperone protein in eukaryotic cells. To resolve which geldanamycin biosynthetic genes are responsible for particular post-polyketide synthase (PKS) processing steps and in which order the reactions occur, we individually inactivated candidate genes in Streptomyces hygroscopicus subsp. duamyceticus JCM4427 and isolated and elucidated the structures of intermediates from each mutant. The results indicated that gel7 governs at least one of the benzoquinone ring oxidation steps. The gel16 was found to be involved in double-bond formation between C-4 and C-5 of 4,5-dihydrogeldanamycin, which confirmed our previous findings that this double bond is reduced during the post-PKS modification of the polyketide assembly. In addition, pro-geldanamycin, which does not possess a double bond at C-4/5, was purified from the gel7 and gel8 double-gene-inactivated mutant.

Keywords

References

  1. August, P. R., L. Tang, Y. J. Yoon, S. Ning, R. Muller, T. W. Yu, et al. 1998. Biosynthesis of the ansamycin antibiotic rifamycin: Deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699. Chem. Biol. 5: 69-79 https://doi.org/10.1016/S1074-5521(98)90141-7
  2. Becker, A. M., A. J. Herlt, G. L. Hilton, J. J. Kibby, and R. W. Rickards. 1983. 3-Amino-5-hydroxybenzoic acid in antibiotic biosynthesis. VI. Directed biosynthesis studies with ansamycin antibiotics. J. Antibiot. 36: 1323-1328 https://doi.org/10.7164/antibiotics.36.1323
  3. Bibb, M. J., J. White, J. M. Ward, and G. R. Janssen. 1994. The mRNA for the 23S rRNA methylase encoded by the ermE gene of Saccharopolyspora erythraea is translated in the absence of a conventional ribosome-binding site. Mol. Microbiol. 14: 533-545 https://doi.org/10.1111/j.1365-2958.1994.tb02187.x
  4. Bierman, M., R. Logan, K. O'Brien, E. T. Seno, R. N. Rao, and B. E. Schoner. 1992. Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116: 43-49 https://doi.org/10.1016/0378-1119(92)90627-2
  5. Cupp-Vickery, J. R. and T. L. Poulos. 1995. Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat. Struct. Biol. 2: 144-153 https://doi.org/10.1038/nsb0295-144
  6. Denis, F. and R. Brzezinski. 1991. An improved aminoglycoside resistance gene cassette for use in Gram-negative bacteria and Streptomyces. FEMS Microbiol. Lett. 81: 261-264 https://doi.org/10.1111/j.1574-6968.1991.tb04769.x
  7. Enroth, C., H. Neujahr, G. Schneider, and Y. Lindqvist. 1998. The crystal structure of phenol hydroxylase in complex with FAD and phenol provides evidence for a concerted conformational change in the enzyme and its cofactor during catalysis. Structure 6: 605-617 https://doi.org/10.1016/S0969-2126(98)00062-8
  8. Eppink, M. H., H. A. Schreuder, and W. J. Van Berkel. 1997. Identification of a novel conserved sequence motif in flavoprotein hydroxylases with a putative dual function in FAD/NAD(P)H binding. Protein Sci. 6: 2454-2458 https://doi.org/10.1002/pro.5560061119
  9. Freel Meyers, C. L., M. Oberthur, H. Xu, L. Heide, D. Kahne, and C. T. Walsh. 2004. Characterization of NovP and NovN: Completion of novobiocin biosynthesis by sequential tailoring of the noviosyl ring. Angew Chem. Int. Ed. Engl. 43: 67-70 https://doi.org/10.1002/anie.200352626
  10. Guan. X., M. B. Fisher, D. H. Lang, Y.-M. Zheng, D. R. Koop, and A. E. Rettie. 1998. Cytochrome P450-dependent desaturation of lauric acid: Isoform selectivity and mechanism of formation of 11-dodecenoic acid. Chem. Biol. Interact. 110: 103- 121 https://doi.org/10.1016/S0009-2797(97)00145-2
  11. Guengerich, F. P. 2001. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14: 611-650 https://doi.org/10.1021/tx0002583
  12. Haber, A., R. D. Johnson, and K. L. Rinehart Jr. 1977. Biosynthetic origin of the C2 units of geldanamycin and distribution of label from D-[$6-^{13}$C]glucose. J. Am. Chem. Soc. 99: 3541-3544 https://doi.org/10.1021/ja00452a079
  13. Hong, Y.-S., D. Lee, W. Kim, J. K. Jeong, C. G. Kim, J. K. Sohng, J. H. Lee, S. G. Paik, and J. J. Lee. 2004. Inactivation of the carbamoyltransferase gene refines post-polyketide synthase modification steps in the biosynthesis of the antitumor agent geldanamycin. J. Am. Chem. Soc. 126: 11142-11143 https://doi.org/10.1021/ja047769m
  14. Hopwood, D. W., M. J. Bibb, K. F. Chater, T. Kieser, C. J. Bruton, H. M. Kieser, et al. 1985. Genetic Manipulation of Streptomyces. A Laboratory Manual. The John Innes Foundation, Norwich, U.K
  15. Johnson, R. D., A. Haber, and K. L. Rinehart Jr. 1974. Geldanamycin biosynthesis and carbon magnetic resonance. J. Am. Chem. Soc. 96: 3316-3317 https://doi.org/10.1021/ja00817a051
  16. Kim, B. C., J. M. Lee., J. S. Ahn, and B. S. Kim. 2007. Cloning, sequencing, and characterization of the pradimicin biosynthetic genes cluster of Actinomadura hibisca. J. Microbiol. Biotechnol. 17: 830-839
  17. Kim, D. Y., Y. K. Park, J. S. Lee, J. H. Kim, H. Y. Jeong, B. S. Kim, and C. H. Lee. 2006. Analysis of a prodigiocin biosynthetic gene cluster from the marine bacterium Hahella chejuensis KCTC 2396. J. Microbiol. Biotechnol. 16: 1912- 1918
  18. Lee, D., K. Lee, X. F. Cai, N. T. Dat, S. K. Boovanahalli, M. Lee, et al. 2006. Biosynthesis of the heat-shock protein 90 inhibitor geldanamycin: New insight into the formation of the benzoquinone moiety. ChemBioChem 7: 246-248 https://doi.org/10.1002/cbic.200500441
  19. Lee, S. K., J. W. Park, S. R. Park, J. S. Ahn, C. Y. Choi, and Y. J. Yoon. 2006. Hydroxylation of indole by PikC cytochrome P450 from Streptomyces venezuelae and engineering its catalytic activity by site-directed mutagenesis. J. Microbiol. Biotechnol. 16: 974-978
  20. Neckers, L. and K. Neckers. 2005. Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics - an update. Expert Opin. Emerg. Drugs 10: 137-149 https://doi.org/10.1517/14728214.10.1.137
  21. Park, N. S., H. J. Park, K. B. Han, and E. S. Kim. 2006. Heterologous expression of novel cytochrome P450 hydroxylase genes from Sebekia benihana. J. Microbiol. Biotechnol. 16: 295-298
  22. Prodromou, C., S. M. Roe, R. O'Brien, J. E. Ladbury, P. W. Piper, and L. H. Pearl. 1997. Identification and structural characterization of the ATP/ADP-binding site in the Hsp90 molecular chaperone. Cell 90: 65-75 https://doi.org/10.1016/S0092-8674(00)80314-1
  23. Rascher, A., Z. Hu, G. O. Buchanan, R. Reid, and C. R. Hutchinson. 2005. Insights into the biosynthesis of the benzoquinone ansamycins geldanamycin and herbimycin, obtained by gene sequencing and disruption. Appl. Environ. Microbiol. 71: 4862-4871 https://doi.org/10.1128/AEM.71.8.4862-4871.2005
  24. Rascher, A., Z. Hu, N. Viswanathan, A. Schirmer, R. Reid, W. C. Nierman, M. Lewis, and C. R. Hutchinson. 2003. Cloning and characterization of a gene cluster for geldanamycin production in Streptomyces hygroscopicus NRRL 3602. FEMS Microbiol. Lett. 218: 223-230 https://doi.org/10.1016/S0378-1097(02)01148-5
  25. Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular Cloning: A Laboratory Manual, 2nd Ed. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York
  26. Xu, J., E. Wan, C. J. Kim, H. G. Floss, and T. Mahmud. 2005. Identification of tailoring genes involved in the modification of the polyketide backbone of rifamycin B by Amycolatopsis mediterranei S699. Microbiology 151: 2515-2528 https://doi.org/10.1099/mic.0.28138-0
  27. Yu, T. W., L. Bai, D. Clade, D. Hoffmann, S. Toelzer, K. Q. Trinh, et al. 2002. The biosynthetic gene cluster of the maytansinoid antitumor agent ansamitocin from Actinosynnema pretiosum. Proc. Natl. Acad. Sci. USA 99: 7968-7973