1887

Abstract

Genome sequencing of A3(2) revealed an uncharacterized type I polyketide synthase gene cluster (). Here we describe the discovery of a novel antibacterial activity (abCPK) and a yellow-pigmented secondary metabolite (yCPK) after deleting a presumed pathway-specific regulatory gene () that encodes a member of the -butyrolactone receptor family of proteins and which lies in the gene cluster. Overproduction of yCPK and abCPK in a deletion mutant, and the absence of the newly described compounds from deletion mutants, suggest that they are products of the previously orphan biosynthetic pathway in which abCPK is converted into the yellow pigment. Transcriptional analysis suggests that may act in a negative feedback mechanism to eventually limit yCPK biosynthesis. The results described here represent a novel approach for the discovery of new, biologically active compounds.

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2010-08-01
2024-03-28
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References

  1. Bentley S. D., Chater K. F., Cerdeno-Tarraga A. M., Challis G. L., Thomson N. R., James K. D., Harris D. E., Quail M. A., Kieser H. other authors 2002; Complete genome sequence of the model actinomycete Streptomyces coelicolor A3(2. Nature 417:141–147
    [Google Scholar]
  2. Bergmann S., Schumann J., Scherlach K., Lange C., Brakhage A. A., Hertweck C. 2007; Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3:213–217
    [Google Scholar]
  3. Bibb M. J. 2005; Regulation of secondary metabolism in streptomycetes. Curr Opin Microbiol 8:208–215
    [Google Scholar]
  4. Bok J. W., Hoffmeister D., Maggio-Hall L. A., Murillo R., Glasner J. D., Keller N. P. 2006; Genomic mining for Aspergillus natural products. Chem Biol 13:31–37
    [Google Scholar]
  5. Bunet R., Mendes M. V., Rouhier N., Pang X., Hotel L., Leblond P., Aigle B. 2008; Regulation of the synthesis of the angucyclinone antibiotic alpomycin in Streptomyces ambofaciens by the autoregulator receptor AlpZ and its specific ligand. J Bacteriol 190:3293–3305
    [Google Scholar]
  6. Bystrykh L. V., Fernandez-Moreno M. A., Herrema J. K., Malpartida F., Hopwood D. A., Dijkhuizen L. 1996; Production of actinorhodin-related “blue pigments” by Streptomyces coelicolor A3(2. J Bacteriol 178:2238–2244
    [Google Scholar]
  7. Challis G. L. 2008; Genome mining for novel natural product discovery. J Med Chem 51:2618–2628
    [Google Scholar]
  8. Challis G. L., Hopwood D. A. 2003; Synergy and contingency as driving forces for the evolution of multiple secondary metabolite production by Streptomyces species. Proc Natl Acad Sci U S A 100 :Suppl. 214555–14561
    [Google Scholar]
  9. Feitelson J. S., Malpartida F., Hopwood D. A. 1985; Genetic and biochemical characterization of the red gene cluster of Streptomyces coelicolor A3(2. J Gen Microbiol 131:2431–2441
    [Google Scholar]
  10. Flett F., Mersinias V., Smith C. P. 1997; High efficiency intergeneric conjugal transfer of plasmid DNA from Escherichia coli to methyl DNA-restricting streptomycetes. FEMS Microbiol Lett 155:223–229
    [Google Scholar]
  11. Gross H. 2007; Strategies to unravel the function of orphan biosynthesis pathways: recent examples and future prospects. Appl Microbiol Biotechnol 75:267–277
    [Google Scholar]
  12. Gust B., Chandra G., Jakimowicz D., Yuqing T., Bruton C. J., Chater K. F. 2004; Lambda red-mediated genetic manipulation of antibiotic-producing Streptomyces. Adv Appl Microbiol 54:107–128
    [Google Scholar]
  13. Hopwood D. A., Wright H. M. 1983; CDA is a new chromosomally-determined antibiotic from Streptomyces coelicolor A3(2. J Gen Microbiol 129:3575–3579
    [Google Scholar]
  14. Hsiao N. H., Soding J., Linke D., Lange C., Hertweck C., Wohlleben W., Takano E. 2007; ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize gamma-butyrolactones. Microbiology 153:1394–1404
    [Google Scholar]
  15. Kieser T., Bibb M. J., Buttner M. J., Chater K. F., Hopwood D. A. 2000 Practical Streptomyces Genetics Norwich, UK: John Innes Foundation;
  16. Kinoshita H., Ipposhi H., Okamoto S., Nakano H., Nihira T., Yamada Y. 1997; Butyrolactone autoregulator receptor protein (BarA) as a transcriptional regulator in Streptomyces virginiae. J Bacteriol 179:6986–6993
    [Google Scholar]
  17. Kuczek K., Pawlik K., Kotowska M., Mordarski M. 1997; Streptomyces coelicolor DNA homologous with acyltransferase domains of type I polyketide synthase gene complex. FEMS Microbiol Lett 157:195–200
    [Google Scholar]
  18. Lakey J. H., Lea E. J., Rudd B. A., Wright H. M., Hopwood D. A. 1983; A new channel-forming antibiotic from Streptomyces coelicolor A3(2) which requires calcium for its activity. J Gen Microbiol 129:3565–3573
    [Google Scholar]
  19. MacNeil D. J., Occi J. L., Gewain K. M., MacNeil T., Gibbons P. H., Ruby C. L., Danis S. J. 1992; Complex organization of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase. Gene 115:119–125
    [Google Scholar]
  20. Matsuno K., Yamada Y., Lee C. K., Nihira T. 2004; Identification by gene deletion analysis of barB as a negative regulator controlling an early process of virginiamycin biosynthesis in Streptomyces virginiae. Arch Microbiol 181:52–59
    [Google Scholar]
  21. Nakamura L. K., Roberts M. S., Cohan F. M. 1999; Relationship of Bacillus subtilis clades associated with strains 168 and W23: a proposal for Bacillus subtilis subsp.subtilis subsp. nov. and Bacillussubtilis subsp. spizizenii subsp. nov. Int J Syst Bacteriol 49:1211–1215
    [Google Scholar]
  22. Nakano H., Takehara E., Nihira T., Yamada Y. 1998; Gene replacement analysis of the Streptomyces virginiae barA gene encoding the butyrolactone autoregulator receptor reveals that BarA acts as a repressor in virginiamycin biosynthesis. J Bacteriol 180:3317–3322
    [Google Scholar]
  23. Nakano H., Lee C. K., Nihira T., Yamada Y. 2000; A null mutant of the Streptomyces virginiae barA gene encoding a butyrolactone autoregulator receptor and its phenotypic and transcriptional analysis. J Biosci Bioeng 90:204–207
    [Google Scholar]
  24. Nieselt K., Battke F., Herbig A., Bruheim P., Wentzel A., Jakobsen O. M., Sletta H., Alam M. T., Merlo M. E. other authors 2010; The dynamic architecture of the metabolic switch in Streptomyces coelicolor. BMC Genomics 11:10
    [Google Scholar]
  25. Omura S., Ikeda H., Ishikawa J., Hanamoto A., Takahashi C., Shinose M., Takahashi Y., Horikawa H., Nakazawa H. other authors 2001; Genome sequence of an industrial microorganism Streptomyces avermitilis: deducing the ability of producing secondary metabolites. Proc Natl Acad Sci U S A 98:12215–12220
    [Google Scholar]
  26. Pawlik K., Kotowska M., Chater K. F., Kuczek K., Takano E. 2007; A cryptic type I polyketide synthase ( cpk) gene cluster in Streptomyces coelicolor A3(2. Arch Microbiol 187:87–99
    [Google Scholar]
  27. Pfoestl A., Hofinger A., Kosma P., Messner P. 2003; Biosynthesis of dTDP-3-acetamido-3,6-dideoxy- α-d-galactose in Aneurinibacillus thermoaerophilus L420–91T. J Biol Chem 278:26410–26417
    [Google Scholar]
  28. Redenbach M., Kieser H. M., Denapaite D., Eichner A., Cullum J., Kinashi H., Hopwood D. A. 1996; A set of ordered cosmids and a detailed genetic and physical map for the 8 Mb Streptomyces coelicolor A3(2) chromosome. Mol Microbiol 21:77–96
    [Google Scholar]
  29. Rigali S., Titgemeyer F., Barends S., Mulder S., Thomae A. W., Hopwood D. A., van Wezel G. P. 2008; Feast or famine: the global regulator DasR links nutrient stress to antibiotic production by Streptomyces. EMBO Rep 9:670–675
    [Google Scholar]
  30. Rudd B. A., Hopwood D. A. 1979; Genetics of actinorhodin biosynthesis by Streptomyces coelicolor A3(2. J Gen Microbiol 114:35–43
    [Google Scholar]
  31. Sambrook J., Russell D. W. 2001 Molecular Cloning: a Laboratory Manual Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
  32. Song L., Barona-Gomez F., Corre C., Xiang L., Udwary D. W., Austin M. B., Noel J. P., Moore B. S., Challis G. L. 2006; Type III polyketide synthase β-ketoacyl-ACP starter unit and ethylmalonyl-CoA extender unit selectivity discovered by Streptomyces coelicolor genome mining. J Am Chem Soc 128:14754–14755
    [Google Scholar]
  33. Takano E. 2006; γ-Butyrolactones: Streptomyces signalling molecules regulating antibiotic production and differentiation. Curr Opin Microbiol 9:287–294
    [Google Scholar]
  34. Takano E., Chakraburtty R., Nihira T., Yamada Y., Bibb M. J. 2001; A complex role for the γ-butyrolactone SCB1 in regulating antibiotic production in Streptomyces coelicolor A3(2. Mol Microbiol 41:1015–1028
    [Google Scholar]
  35. Takano E., Kinoshita H., Mersinias V., Bucca G., Hotchkiss G., Nihira T., Smith C. P., Bibb M., Wohlleben W. other authors 2005a; A bacterial hormone (the SCB1) directly controls the expression of a pathway-specific regulatory gene in the cryptic type I polyketide biosynthetic gene cluster of Streptomyces coelicolor. Mol Microbiol 56:465–479
    [Google Scholar]
  36. Takano H., Obitsu S., Beppu T., Ueda K. 2005b; Light-induced carotenogenesis in Streptomyces coelicolor A3(2): identification of an extracytoplasmic function sigma factor that directs photodependent transcription of the carotenoid biosynthesis gene cluster. J Bacteriol 187:1825–1832
    [Google Scholar]
  37. Tang J. S., Gillevet P. M. 2003; Reclassification of ATCC 9341 from Micrococcus luteus to Kocuria rhizophila. Int J Syst Evol Microbiol 53:995–997
    [Google Scholar]
  38. Udwary D. W., Zeigler L., Asolkar R. N., Singan V., Lapidus A., Fenical W., Jensen P. R., Moore B. S. 2007; Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica. Proc Natl Acad Sci U S A 104:10376–10381
    [Google Scholar]
  39. Widdick D. A., Dilks K., Chandra G., Bottrill A., Naldrett M., Pohlschroder M., Palmer T. 2006; The twin-arginine translocation pathway is a major route of protein export in Streptomyces coelicolor. Proc Natl Acad Sci U S A 103:17927–17932
    [Google Scholar]
  40. Yang K., Han L., Vining L. C. 1995; Regulation of jadomycin B production in Streptomyces venezuelae ISP5230: involvement of a repressor gene, jadR2. J Bacteriol 177:6111–6117
    [Google Scholar]
  41. Zerikly M., Challis G. L. 2009; Strategies for the discovery of new natural products by genome mining. ChemBioChem 10:625–633
    [Google Scholar]
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