Browse > Article

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))
Publication Information
Journal of Microbiology and Biotechnology / v.18, no.6, 2008 , pp. 1101-1108 More about this Journal
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
Geldanamycin; biosynthesis; Streptomyces; polyketide;
Citations & Related Records
Times Cited By KSCI : 4  (Citation Analysis)
Times Cited By Web Of Science : 12  (Related Records In Web of Science)
연도 인용수 순위
1 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   DOI
2 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   DOI   ScienceOn
3 Guengerich, F. P. 2001. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol. 14: 611-650   DOI   ScienceOn
4 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   과학기술학회마을
5 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   DOI   ScienceOn
6 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   DOI   ScienceOn
7 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
8 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   DOI   ScienceOn
9 Neckers, L. and K. Neckers. 2005. Heat-shock protein 90 inhibitors as novel cancer chemotherapeutics - an update. Expert Opin. Emerg. Drugs 10: 137-149   DOI   ScienceOn
10 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   DOI   ScienceOn
11 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   DOI
12 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   과학기술학회마을
13 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
14 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   과학기술학회마을
15 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   과학기술학회마을
16 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   DOI
17 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   DOI   ScienceOn
18 Johnson, R. D., A. Haber, and K. L. Rinehart Jr. 1974. Geldanamycin biosynthesis and carbon magnetic resonance. J. Am. Chem. Soc. 96: 3316-3317   DOI
19 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   DOI   ScienceOn
20 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   DOI   ScienceOn
21 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   DOI   ScienceOn
22 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   DOI   ScienceOn
23 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   DOI   ScienceOn
24 Cupp-Vickery, J. R. and T. L. Poulos. 1995. Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat. Struct. Biol. 2: 144-153   DOI   ScienceOn
25 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   DOI   ScienceOn
26 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   DOI   ScienceOn
27 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