Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Discovery of a natural thiamine adenine nucleotide

Nature Chemical Biology volume 3, pages 211–212 (2007)Cite this article

Abstract

Several important cofactors are adenine nucleotides with a vitamin as the catalytic moiety. Here, we report the discovery of the first adenine nucleotide containing vitamin B1: adenosine thiamine triphosphate (AThTP, 1), or thiaminylated ATP. We discovered AThTP in Escherichia coli and found that it accumulates specifically in response to carbon starvation, thereby acting as a signal rather than a cofactor. We detected smaller amounts in yeast and in plant and animal tissues.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Chromatograms showing the presence of ThTP or the additional peak, according to culture conditions.
Figure 2: Effect of substrate addition on the content of AThTP and ThTP in E.coli

Similar content being viewed by others

References

  1. Makarchikov, A.F. et al. Cell. Mol. Life Sci. 60, 1477–1488 (2003).

    Article  CAS  Google Scholar 

  2. Wille, G. et al. Nat. Chem. Biol. 2, 324–328 (2006).

    Article  CAS  Google Scholar 

  3. Lakaye, B., Wirtzfeld, B., Wins, P., Grisar, T. & Bettendorff, L. J. Biol. Chem. 279, 17142–17147 (2004).

    Article  CAS  Google Scholar 

  4. Bettendorff, L., Nghiêm, H.O., Wins, P. & Lakaye, B. Anal. Biochem. 322, 190–197 (2003).

    Article  CAS  Google Scholar 

  5. Cashel, M. & Gallant, J. Nature 221, 838–841 (1969).

    Article  CAS  Google Scholar 

  6. Artsimovitch, I. et al. Cell 117, 299–310 (2004).

    Article  CAS  Google Scholar 

  7. Chatterjee, A., Jurgenson, C.T., Schroeder, F., Ealick, S.E. & Begley, T.P. J. Am. Chem. Soc. 128, 7158–7159 (2006).

    Article  CAS  Google Scholar 

  8. Bettendorff, L., Peeters, M., Jouan, C., Wins, P. & Schoffeniels, E. Anal. Biochem. 198, 52–59 (1991).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grant 2.4558.04 from the Fonds de la Recherche Fondamentale Collective and by grants from the Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture to B.W. and M.G. M.F. and L.B. are respectively Research Associate and Senior Research Associate at the Fonds de la Recherche Scientifique–FNRS. The authors thank D. Baiwir for help with MS and I. Margineanu for helpful comments on the manuscript.

Author information

Author notes

  1. Lucien Bettendorff and Barbara Wirtzfeld: These authors contributed equally to this work.

Authors and Affiliations

  1. Center for Cellular and Molecular Neurobiology, University of Liège, Avenue de l'Hôpital 1, Liège, B-4000, Belgium

    Lucien Bettendorff, Barbara Wirtzfeld, Alexander F Makarchikov, Tiziana Gigliobianco, Marjorie Gangolf & Pierre Wins

  2. Department of Physical Chemistry, University of Liège, Allée de la Chimie 3, Liège, B-4000, Belgium

    Gabriel Mazzucchelli & Edwin De Pauw

  3. Laboratory of Pharmacognosy, Drug Research Center, University of Liège, Avenue de l'Hôpital 1, Liège, B-4000, Belgium

    Michel Frédérich & Luc Angenot

Authors
  1. Lucien Bettendorff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara Wirtzfeld
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alexander F Makarchikov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gabriel Mazzucchelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michel Frédérich
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tiziana Gigliobianco
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marjorie Gangolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Edwin De Pauw
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Luc Angenot
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pierre Wins
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

L.B. is the project leader and performed purification of the bacterial AThTP and chemical synthesis and purification of AThTP. B.W. discovered the AThTP peak on the chromatograms, performed part of the experiments with bacteria and started the purification. A.F.M. helped to identify AThTP and studied its enzymatic synthesis and hydrolysis. G.M. and E.P. performed MS experiments. M.F and L.A. performed NMR experiments. T.G. performed part of the experiments with bacteria. M.G. measured AThTP in animal tissues. P.W. helped to design the experiments and write the paper.

Corresponding author

Correspondence to Lucien Bettendorff.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Purification of AThTP on a Polaris C18 HPLC column. (PDF 85 kb)

Supplementary Fig. 2

Mass spectrometry. (PDF 464 kb)

Supplementary Fig. 3

NMR data. (PDF 280 kb)

Supplementary Fig. 4

Enzymatic hydrolysis of AThTP. (PDF 109 kb)

Supplementary Table 1

Purification of AThTP from E. coli. (PDF 91 kb)

Supplementary Table 2

Effect of media composition on the content of ThTP and AThTP in E. coli. (PDF 68 kb)

Supplementary Table 3

Occurrence of AThTP and ThTP in eukaryotic organisms. (PDF 108 kb)

Supplementary Methods (PDF 94 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bettendorff, L., Wirtzfeld, B., Makarchikov, A. et al. Discovery of a natural thiamine adenine nucleotide. Nat Chem Biol 3, 211–212 (2007). https://doi.org/10.1038/nchembio867

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio867

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing