Browse > Article
http://dx.doi.org/10.4014/jmb.1005.05040

Identification of Three Positive Regulators in the Geldanamycin PKS Gene Cluster of Streptomyces hygroscopicus JCM4427  

Kim, Won-Cheol (Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Lee, Jung-Joon (Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Paik, Sang-Gi (Chungnam National University)
Hong, Young-Soo (Korea Research Institute of Bioscience and Biotechnology (KRIBB))
Publication Information
Journal of Microbiology and Biotechnology / v.20, no.11, 2010 , pp. 1484-1490 More about this Journal
Abstract
In the Streptomyces hygroscopicus JCM4427 geldanamycin biosynthetic gene cluster, five putative regulatory genes were identified by protein homology searching. Among those genes, gel14, gel17, and gel19 are located downstream of polyketide synthase genes. Gel14 and Gel17 are members of the LAL family of transcriptional regulators, including an ATP/GTP-binding domain at the N-terminus and a DNA-binding helix-turn-helix domain at the C-terminus. Gel19 is a member of the TetR family of transcriptional regulators, which generally act to repress transcription. To verify the biological significance of the putative regulators in geldanamycin production, they were individually characterized by gene disruption, genetic complementation, and transcriptional analyses. All three genes were confirmed as positive regulators of geldanamycin production. Specifically, Gel17 and Gel19 are required for gel14 as well as gelA gene expression.
Keywords
Regulator; geldanamycin; biosynthesis; Streptomyces;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 1  (Related Records In Web of Science)
연도 인용수 순위
1 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
2 Henikoff, S., J. C. Wallace, and J. P. Brown. 1990. Finding protein similarities with nucleotide sequence databases. Methods Enzymol. 183: 111-132.   DOI
3 Horinouchi, S., M. Kito, M. Nishiyama, K. Furuya, S.-K. Hong, K. Miyake, and T. Beppu. 1990. Primary structure of AfsR, a global regulatory protein for secondary metabolite formation in Streptomyces coelicolor $A_{3}$(2). Gene 95: 49-56.   DOI   ScienceOn
4 Le, T. B., H. P. Fiedler, C. D. den Hengst, S. K. Ahn, A. Maxwell, and M. J. Buttner. 2009. Coupling of the biosynthesis and export of the DNA gyrase inhibitor simocyclinone in Streptomyces antibioticus. Mol. Microbiol. 72: 1462-1474.   DOI   ScienceOn
5 Wilson, D. J., Y. Xue, K. A. Reynolds, and D. H. Sherman. 2001. Characterization and analysis of the PikD regulatory factor in the pikromycin biosynthetic pathway of Streptomyces venezuelae. J. Bacteriol. 183: 3468-3475.   DOI   ScienceOn
6 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.
7 Shin, J. C., Z. Na, D. H. Lee, W. C. Kim, K. Lee, Y. M. Shen, S. G. Paik, Y.-S. Hong, and J. J. Lee. 2008. Characterization of tailoring genes involved in the modification of geldanamycin polyketide in Streptomyces hygroscopicus $JCM_{4427}$. J. Microbiol. Biotechnol. 18: 1101-1108.   과학기술학회마을
8 Uguru, G. C., K. E. Stephens, J. A. Stead, J. E. Towle, S. Baumberg, and K. J. McDowall. 2005. Transcriptional activation of the pathway-specific regulator of the actinorhodin biosynthetic genes in Streptomyces coelicolor. Mol. Microbiol. 58: 131-150.   DOI   ScienceOn
9 Walker, J. E., M. Saraste, M. J. Runswick, and N. J. Gay. 1982. Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold. EMBO J. 1: 945-951.
10 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
11 Park, U.-M., J.-W. Suh, and S.-K. Hong. 2000. Genetic analysis of absR, a new abs locus of Streptomyces coelicolor. J. Microbiol. Biotechnol. 10: 169-175.
12 Sheldon, P. J., S. B. Busarow, and C. R. Hutchinson. 2002. Mapping the DNA-binding domain and target sequences of the Streptomyces peucetius daunorubicin biosynthesis regulatory protein, DnrI. Mol. Microbiol. 44: 449-460.   DOI   ScienceOn
13 Neckers, L. and Y. S. Lee. 2003. Cancer: The rules of attraction. Nature 425: 357-359.   DOI   ScienceOn
14 Orth, P., D. Schnappinger, W. Hillen, W. Saenger, and W. Hinrichs. 2000. Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system. Nat. Struct. Biol. 7: 215-219.   DOI   ScienceOn
15 Ramos, J. L., M. Martinez-Bueno, A. J. Molina-Henares, W. Teran, K. Watanabe, X. Zhang, M. T. Gallegos, R. Brennan, and R. Tobes. 2005. The TetR family of transcriptional repressors. Microbiol. Mol. Biol. Rev. 69: 326-356.   DOI   ScienceOn
16 Knirschova, R., R. Novakova, L. Feckova, J. Timko, J. Turna, J. Bistakova, and J. Kormanec. 2007. Multiple regulatory genes in the salinomycin biosynthetic gene cluster of Streptomyces albus $CCM _{4719}$. Folia Microbiol. (Praha) 52: 359-365.   DOI   ScienceOn
17 Kitani, S., H. Ikeda, T. Sakamoto, S. Noguchi, and T. Nihira. 2009. Characterization of a regulatory gene, aveR, for the biosynthesis of avermectin in Streptomyces avermitilis. Appl. Microbiol. Biotechnol. 82: 1089-1096.   DOI   ScienceOn
18 Kuscer, E., N. Coates, I. Challis, M. Gregory, B. Wilkinson, R. Sheridan, and H. Petkovic. 2007. Roles of rapH and rapG in positive regulation of rapamycin biosynthesis in Streptomyces hygroscopicus. J. Bacteriol. 189: 4756-4763.   DOI   ScienceOn
19 Hur, Y. A., S. S. Choi, D. H. Sherman, and E. S. Kim. 2008. Identification of TmcN as a pathway-specific positive regulator of tautomycetin biosynthesis in Streptomyces sp. $CK_{4412}$. Microbiology 154: 2912-2919.   DOI   ScienceOn
20 Kim, W. 2008. Engineered Biosynthesis and identification of regulaory genes in geldanamycin biosynthesis. Ph. D. Thesis. Chungnam National University, Daejeon.
21 He, W., J. Lei, Y. Liu, and Y. Wang. 2008. The LuxR family members GdmRI and GdmRII are positive regulators of geldanamycin biosynthesis in Streptomyces hygroscopicus 17997. Arch. Microbiol. 189: 501-510.   DOI   ScienceOn
22 He, W., L. Wu, Q. Gao, Y. Du, and Y. Wang. 2006. Identification of AHBA biosynthetic genes related to geldanamycin biosynthesis in Streptomyces hygroscopicus 17997. Curr. Microbiol. 52: 197-203.   DOI   ScienceOn
23 Hinrichs, W., C. Kisker, M. Duvel, A. Muller, K. Tovar, W. Hillen, and W. Saenger. 1994. Structure of the Tet repressortetracycline complex and regulation of antibiotic resistance. Science 264: 418-420.   DOI
24 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
25 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
26 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, UK.
27 Ahn, S. K., K. Tahlan, Z. Yu, and J. Nodwell. 2007. Investigation of transcription repression and small-molecule responsiveness by TetR-like transcription factors using a heterologous Escherichia coli-based assay. J. Bacteriol. 189: 6655-6664.   DOI   ScienceOn
28 Bibb, M. J. 2005. Regulation of secondary metabolism in streptomycetes. Curr. Opin. Microbiol. 8: 208-215.   DOI   ScienceOn
29 De Schrijver, A. and R. De Mot. 1999. A subfamily of MalTrelated ATP-dependent regulators in the LuxR family. Microbiology 145: 1287-1288.   DOI   ScienceOn
30 Guilfoile, P. G. and C. R. Hutchinson. 1992. The Streptomyces glaucescens TcmR protein represses transcription of the divergently oriented tcmR and tcmA genes by binding to an intergenic operator region. J. Bacteriol. 174: 3659-3666.