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A new thiamin salvage pathway

Nature Chemical Biology volume 3, pages 492–497 (2007)Cite this article

Abstract

The physiological function for thiaminase II, a thiamin-degrading enzyme, has eluded investigators for more than 50 years. Here, we demonstrate that this enzyme is involved in the regeneration of the thiamin pyrimidine rather than in thiamin degradation, and we identify a new pathway involved in the salvage of base-degraded forms of thiamin. This pathway is widely distributed among bacteria, archaea and eukaryotes. In this pathway, thiamin hydrolysis products such as N-formyl-4-amino-5-aminomethyl-2-methylpyrimidine (formylaminopyrimidine; 15) are transported into the cell using the ThiXYZ transport system, deformylated by the ylmB-encoded amidohydrolase and hydrolyzed to 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP; 6)—an intermediate on the de novo thiamin biosynthetic pathway. To our knowledge this is the first example of a thiamin salvage pathway involving thiamin analogs generated by degradation of one of the heterocyclic rings of the cofactor.

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Figure 1: Formation of formylaminopyrimidine and its identification in a mixture of thiamin degraded in the presence of soil.

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Acknowledgements

We would like to thank C. Kinsland (Protein Purification Facility, Cornell University) for overexpressing TenA and J. Hanes for his help with the Kd determination. We would also like to thank Roche for providing aminopyrimidine. This research was supported by a grant from the US National Institutes of Health (DK44083).

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, 14853, New York, USA

    Amy Haas Jenkins, Guangxing Sun & Tadhg P Begley

  2. Biotechnology R&D, DSM Nutritional Products, PO box 3255, Bldg 203/25, Basel, CH-4002, Switzerland

    Ghislain Schyns & Sébastien Potot

Authors
  1. Amy Haas Jenkins
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  4. Guangxing Sun
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  5. Tadhg P Begley
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Correspondence to Tadhg P Begley.

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Supplementary Figures 1–6 and Supplementary Table 1 (PDF 351 kb)

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Jenkins, A., Schyns, G., Potot, S. et al. A new thiamin salvage pathway. Nat Chem Biol 3, 492–497 (2007). https://doi.org/10.1038/nchembio.2007.13

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