Investigating the role of the hydroxyl groups of substrate erythrose 4-phosphate in the reaction catalysed by the first enzyme of the shikimate pathway

Bioorg Med Chem Lett. 2011 Nov 15;21(22):6838-41. doi: 10.1016/j.bmcl.2011.09.017. Epub 2011 Sep 16.


3-Deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) synthase catalyses the first step of the shikimate pathway, which is responsible for the biosynthesis of aromatic amino acids in microorganisms and plants. This enzyme catalyses an aldol reaction between phosphoenolpyruvate and D-erythrose 4-phosphate to generate DAH7P. Both 2-deoxyerythrose 4-phosphate and 3-deoxyerythrose 4-phosphate were synthesised and tested as alternative substrates for the enzyme. Both compounds were found to be substrates for the DAH7P synthases from Escherichia coli, Pyrococcus furiosus and Mycobacterium tuberculosis, consistent with an acyclic mechanism for the enzyme for which neither C2 nor C3 hydroxyl groups are required for catalysis. The enzymes all showed greater tolerance for the loss of the C2 hydroxyl group than the C3 hydroxyl group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Deoxy-7-Phosphoheptulonate Synthase / metabolism*
  • Escherichia coli / enzymology*
  • Models, Molecular
  • Mycobacterium tuberculosis / enzymology*
  • Pyrococcus furiosus / enzymology*
  • Shikimic Acid / metabolism
  • Substrate Specificity
  • Sugar Phosphates / chemistry
  • Sugar Phosphates / metabolism*


  • Sugar Phosphates
  • Shikimic Acid
  • erythrose 4-phosphate
  • 3-Deoxy-7-Phosphoheptulonate Synthase