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Bacillithiol is an antioxidant thiol produced in Bacilli

Nature Chemical Biology volume 5, pages 625–627 (2009)Cite this article

Abstract

Glutathione is a nearly ubiquitous, low-molecular-mass thiol and antioxidant, but it is conspicuously absent from most Gram-positive bacteria. We identify here the structure of bacillithiol, a newly described and abundant thiol produced by Bacillus species, Staphylococcus aureus and Deinococcus radiodurans. Bacillithiol is the α-anomeric glycoside of L-cysteinyl-D-glucosamine with L-malic acid and most probably functions as an antioxidant. Bacillithiol, like the structurally similar mycothiol, may serve as a substitute for glutathione.

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Figure 1: The hydrolysis of 8 defines its composition.
Figure 2: NMR studies confirm the composition of 8, establish linkage in 8 and define the structure of bacillithiol.

References

  1. Held, K.D. & Biaglow, J.E. Radiat. Res. 139, 15–23 (1994).

    Article  CAS  Google Scholar 

  2. Fahey, R.C. & Sundquist, A.R. Adv. Enzymol. 64, 1–53 (1991).

    CAS  PubMed  Google Scholar 

  3. Meister, A. in Glutathione: Chemical, Biochemical, and Medical Aspects part A (eds. Dolphin, D., Poulson, R. & Avramovic, O.) 367–474 (Wiley, New York, 1989).

    Google Scholar 

  4. Fahey, R.C., Brown, W.C., Adams, W.B. & Worsham, M.B. J. Bacteriol. 133, 1126–1129 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Jothivasan, V.K. & Hamilton, C.J. Nat. Prod. Rep. 25, 1091–1117 (2008).

    Article  CAS  Google Scholar 

  6. Newton, G.L., Buchmeier, N. & Fahey, R.C. Microbiol. Mol. Biol. Rev. 72, 471–494 (2008).

    Article  CAS  Google Scholar 

  7. Rawat, M. & Av-Gay, Y. FEMS Microbiol. Rev. 31, 278–292 (2007).

    Article  CAS  Google Scholar 

  8. Newton, G.L. et al. Eur. J. Biochem. 230, 821–825 (1995).

    Article  CAS  Google Scholar 

  9. Patel, M.P. & Blanchard, J.S. Biochemistry 38, 11827–11833 (1999).

    Article  CAS  Google Scholar 

  10. Fahey, R.C. & Newton, G.L. in Functions of Glutathione: Biochemical, Physiological, Toxicological and Clinical Aspects (eds. Larsson, A., Orrenius, S., Holmgren, A. & Mannervik, B.) 251–260 (Raven, New York, 1983).

    Google Scholar 

  11. delCardayré, S.B., Stock, K.P., Newton, G.L., Fahey, R.C. & Davies, J.E. J. Biol. Chem. 273, 5744–5751 (1998).

    Article  Google Scholar 

  12. delCardayré, S.B. & Davies, J.E. J. Biol. Chem. 273, 5752–5757 (1998).

    Article  Google Scholar 

  13. Nicely, N.I. et al. Biochemistry 46, 3234–3245 (2007).

    Article  CAS  Google Scholar 

  14. Lee, J.W., Soonsanga, S. & Helmann, J.D. Proc. Natl. Acad. Sci. USA 104, 8743–8748 (2007).

    Article  CAS  Google Scholar 

  15. Soonsanga, S., Lee, J.W. & Helmann, J.D. Mol. Microbiol. 68, 978–986 (2008).

    Article  CAS  Google Scholar 

  16. Rotzoll, N., Dunkel, A. & Hofmann, T. J. Agric. Food Chem. 53, 4149–4156 (2005).

    Article  CAS  Google Scholar 

  17. Hermansson, K., Kenne, L., Rukunga, G.M. & Samuelsson, G. Phytochemistry 29, 513–515 (1990).

    Article  CAS  Google Scholar 

  18. Lithgow, J.K., Hayhurst, E.J., Cohen, G., Aharonowitz, Y. & Foster, S.J. J. Bacteriol. 186, 1579–1590 (2004).

    Article  CAS  Google Scholar 

  19. Wallen, J.R., Paige, C., Mallett, T.C., Karplus, P.A. & Claiborne, A. Biochemistry 47, 5182–5193 (2008).

    Article  CAS  Google Scholar 

  20. Hoch, J.A. & Coukoulis, H.J. J. Bacteriol. 133, 265–269 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Mostertz, J., Hochgrafe, F., Jurgen, B., Schweder, T. & Hecker, M. Proteomics 8, 2676–2690 (2008).

    Article  CAS  Google Scholar 

  22. Holmgren, A. Annu. Rev. Biochem. 54, 237–271 (1985).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank H. Upton for technical assistance. This work was supported by grants from the US National Science Foundation to R.C.F. (MCB0235705) and J.D.H. (MCB0640616); from the US National Institutes of Health to R.C.F. (AI49174 and AI072133), to M.R. (GM061223-05A) and to A.C. (GM35394); and from The University of East Anglia to V.K.J.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California, USA

    Gerald L Newton, James J La Clair, Tanya Budiarto & Robert C Fahey

  2. Department of Biology, California State University-Fresno, Fresno, California, USA

    Mamta Rawat

  3. School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich, UK

    Vishnu Karthik Jothivasan & Chris J Hamilton

  4. Center for Structural Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA

    Al Claiborne

  5. Department of Microbiology, Cornell University, Ithaca, New York, USA

    John D Helmann

Authors
  1. Gerald L Newton
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  2. Mamta Rawat
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  3. James J La Clair
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  4. Vishnu Karthik Jothivasan
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  8. John D Helmann
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  9. Robert C Fahey
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Contributions

M.R. and G.L.N. prepared bacterial cultures for isolation of 8 and the survey of thiol distribution. G.L.N. and T.B. purified 8; G.L.N. conducted the hydrolysis of 8 and the HPLC and enzymatic analyses. J.J.L. and G.L.N. conducted the NMR analysis of 8, 11 and 12. V.K.J. and C.J.H. synthesized proposed hydrolysis intermediates 11 and 12. G.L.N., M.R., J.J.L., C.J.H., A.C., J.D.H. and R.C.F. developed the project and interpreted the results. All authors contributed to the writing.

Corresponding author

Correspondence to Robert C Fahey.

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Competing interests

G.L.N., M.R., J.J.L. and R.C.F. will attempt to patent bacillithiol, its biosynthetic precursors, and its biosynthetic and metabolic proteins.

Supplementary information

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Supplementary Figures 1–3, Supplementary Tables 1–4 and Supplementary Methods (PDF 2812 kb)

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Newton, G., Rawat, M., La Clair, J. et al. Bacillithiol is an antioxidant thiol produced in Bacilli. Nat Chem Biol 5, 625–627 (2009). https://doi.org/10.1038/nchembio.189

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