Negative Role of wblA in Response to Oxidative Stress in Streptomyces coelicolor

  • Kim, Jin-Su (Department of Biological Engineering, Inha University) ;
  • Lee, Han-Na (Department of Biological Engineering, Inha University) ;
  • Kim, Pil (Department of Biotechnology, The Catholic University of Korea) ;
  • Lee, Heung-Shick (Department of Biotechnology and Bioinformatics, Korea University) ;
  • Kim, Eung-Soo (Department of Biological Engineering, Inha University)
  • Received : 2011.12.16
  • Accepted : 2012.01.25
  • Published : 2012.06.28


In this study, we analyzed the oxidative stress response of wblA ($\underline{w}$hi$\underline{B}$-$\underline{l}$ike gene $\underline{A}$, SCO3579), which was previously shown to be a global antibiotic down-regulator in Streptomyces coelicolor. Ever since a WblA ortholog named WhcA in Corynebacterium glutamicum was found to play a negative role in the oxidative stress response, S. coelicolor wblA has been proposed to have a similar effect. A wblA-deletion mutant exhibited a less sensitive response to oxidative stress induced by diamide present in solid plate culture. Using real-time RT-PCR analysis, we also compared the transcription levels of oxidative stress-related genes, including sodF, sodF2, sodN, trxB, and trxB2, between S. coelicolor wild type and a wblA-deletion mutant in the presence or absence of oxidative stress. Target genes were expressed higher in the wblA-deletion mutant compared with wild type, both in the absence and presence of oxidative stress. Moreover, expression of these target genes in S. coelicolor wild type was stimulated only in the presence of oxidative stress, suggesting that WblA plays a negative role in the oxidative stress response of S. coelicolor, similar to that of C. glutamicum WhcA, through the transcriptional regulation of oxidative stress-related genes.


Supported by : National Research Foundation of Korea (NRF)


  1. Arner, E. S. and A. Holmgren. 2000. Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 267: 6102-6109.
  2. Choi, S. U., C. K. Lee, Y. I. Hwang, H. Kinoshita, and T. Nihira. 2004. Intergeneric conjugal transfer of plasmid DNA from Escherichia coli to Kitasatospora setae, a bafilomycin B1 producer. Arch. Microbiol. 181: 294-298.
  3. Choi, W. W., S. D. Park, S. M. Lee, H. B. Kim, Y. Kim, and H. S. Lee. 2008. The whcA gene plays a negative role in oxidative stress response of Corynebacterium glutamicum. FEMS Microbiol. Lett. 290: 32-38.
  4. Chung, H. J., E. J. Kim, B. Suh, J. H. Choi, and J. H. Roe. 1999. Duplicate genes for Fe-containing superoxide dismutase in Streptomyces coelicolor A3(2). Gene 231: 87-93.
  5. Crack, J. C., C. D. den Hengst, P. Jakimowicz, S. Subramanian, M. K. Jhonson, M. J. Buttner, et al. 2009. Characterization of [4Fe-4S]-containing and cluster-free forms of Streptomyces WhiD. Biochemistry 48: 12252-12264.
  6. Crack, J. C., L. J. Smith, M. R. Stapleton, J. Peck, N. J. Watmough, M. J. Buttner, et al. 2011. Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of WhiB-like protein. J. Am. Chem. Soc. 133: 1112-1121.
  7. Davis, N. K. and K. F. Chater. 1992. The Streptomyces coelicolor whiB gene encodes a small transcription factor-like protein dispensable for growth but essential for sporulation. Mol. Gen. Genet. 232: 351-358.
  8. den Hengst, C. D. and M. J. Buttner. 2008. Redox control in actinobacteria. Biochem. Biophys. Acta 1780: 1201-1216.
  9. Goldsworthy, K. F., B. Gust, S. Mouz, G. Chandra, K. C. Findlay, and K. F. Chater. 2011. The actinobacteria-specific gene wblA controls major development transition in Streptomyces coelicolor A3(2). Microbiology 157: 1312-1328.
  10. Gladyshev, V. N. 2001. Thioredoxin and peptide methionine sulfoxide reductase: Convergence of similar structure and function in distinct structural folds. Protein 46: 149-152.
  11. Jakimowicz, P., M. R. Cheesman, W. R. Bishai, K. F. Chater, A. J. Thomson, and M. J. Buttner. 2005. Evidence that the Streptomyces developmental protein WhiD, a member of the WhiB family, binds a [4Fe-4S] cluster. J. Biol. Chem. 280: 8309-8315.
  12. Kang, S. H., J. Huang, H. N. Lee, Y. A. Hur, S. N. Cohen, and E. S. Kim. 2007. Interspecies DNA microarray analysis identifies WblA as a pleiotropic down-regulator of antibiotic biosynthesis in Streptomyces. J. Bacteriol. 189: 4315-4319.
  13. Kim, E. J., H. J. Chung, B. Suh, Y. C. Hah, and J. H. Roe. 1998. Expression and regulation of the sodF gene encoding iron- and zinc-containing superoxide dismutase in Streptomyces coelicolor Miller. J. Bacteriol. 180: 2014-2020.
  14. Kim, E. J., H. P. Kim, Y. C. Hah, and J. H. Roe. 1996. Differential expression of superoxide dismutases containing Ni and Fe/Zn in Streptomyces coelicolor. Eur. J. Biochem. 241: 178-185.
  15. Kim, T. H., J. S. Park, H. J. Kim, Y. Kim, P. Kim, and H. S. Lee. 2005. The whcE gene of Corynebacterium glutamicum is important for survival following heat and oxidative stress. Biochem. Biophys. Res. Commun. 337: 757-764.
  16. Mustacich, D. and G. Powis. 2000. Thioredoxin reductase. Biochem. J. 346: 1-8.
  17. Paget, M. S., J. G. Kang, J. H. Roe, and M. J. Buttner. 1998. SigmaR, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2). EMBO J. 19: 5776-5782.
  18. Park, J. S., S. Shin, E. S. Kim, P. Kim, Y. Kim, and H. S. Lee. 2011. Identification of SpiA that interacts with Corynebacterium glutamicum WhcA using a two-hybrid system. FEMS Microbiol. Lett. 322: 8-14.
  19. Singh, A., L. Guidry, K. V. Narasimhulu, D. Mai, J. Trombley, K. E. Redding, et al. 2007. Mycobacterium tuberculosis WhiB3 responds to $O_2$ and nitric oxide via its [4Fe-4S] cluster and is essential for nutrient starvation survival. Proc. Natl. Acad. Sci. USA 104: 11562-11567.
  20. Soliveri, J. A., J. Gomez, W. R. Bishai, and K. F. Chater. 2000. Multiple paralogous genes related to the Streptomyces coelicolor developmental regulatory gene whiB are present in Streptomyces and other actinomycetes. Microbiology 146: 333-343.