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A strictly monofunctional bacterial hydroxymethylpyrimidine phosphate kinase precludes damaging errors in thiamin

Antje M Thamm1, Gengnan Li2, Marlene Taja-Moreno1

  • 1Horticultural Sciences, University of Florida, Gainesville, Florida, FL 32611-0690, United States.

The Biochemical Journal
|July 22, 2017
PubMed

Insights

A newly discovered enzyme, ThiD2, specifically phosphorylates hydroxymethylpyrimidine monophosphate, preventing toxic analogs from entering the thiamin pathway. This monofunctional kinase offers a safer alternative to the canonical ThiD enzyme.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Enzymology

Background:

  • The canonical thiamin biosynthesis kinase, ThiD, phosphorylates hydroxymethylpyrimidine (HMP) monophosphate to diphosphate.
  • ThiD also phosphorylates free HMP, enabling salvage but allowing toxic analogs into the pathway.

Purpose of the Study:

  • To identify and characterize a potential replacement for ThiD that avoids toxic analog infiltration.
  • To investigate the function of the newly discovered thiD2 gene.

Main Methods:

  • Comparative genomic analysis to identify thiD2.
  • Genetic and biochemical analyses of ThiD2 proteins (standalone and fused).

Main Results:

  • thiD2 genes are often fused to thiE and encode small, novel proteins.
  • ThiD2 proteins specifically phosphorylate HMP monophosphate, not HMP or toxic analogs.
  • ThiD2 functions as a strictly monofunctional HMP monophosphate kinase.

Conclusions:

  • ThiD2 proteins provide a solution to the substrate-non-specificity of ThiD.
  • This specificity eliminates a vulnerability in thiamin biosynthesis, albeit at the cost of HMP salvage.
  • ThiD2 represents a significant advancement in understanding and potentially engineering thiamin synthesis pathways.
Keywords:
4-Amino-5-hydroxymethyl-2-methylpyrimidineKinetic characterizationSalvageThiaminVitamin B1

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