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Discovery of a natural thiamine adenine nucleotide


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.

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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


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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.

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Authors and Affiliations



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.

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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)

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Bettendorff, L., Wirtzfeld, B., Makarchikov, A. et al. Discovery of a natural thiamine adenine nucleotide. Nat Chem Biol 3, 211–212 (2007).

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