Identification of a novel glyoxylate reductase supports phylogeny-based enzymatic substrate specificity prediction

Biochim Biophys Acta. 2007 Sep;1774(9):1092-8. doi: 10.1016/j.bbapap.2007.06.009. Epub 2007 Jul 6.


Phylogenetic analysis of the superfamily of D-2-hydroxyacid dehydrogenases identified the previously unrecognized cluster of glyoxylate/hydroxypyruvate reductases (GHPR). Based on the genome sequence of Rhizobium etli, the nodulating endosymbiont of the common bean plant, we predicted a putative 3-phosphoglycerate dehydrogenase to exhibit GHPR activity instead. The protein was overexpressed and purified. The enzyme is homodimeric under native conditions and is indeed capable of reducing both glyoxylate and hydroxypyruvate. Other substrates are phenylpyruvate and ketobutyrate. The highest activity was observed with glyoxylate and phenylpyruvate, both having approximately the same kcat/Km ratio. This kind of substrate specificity has not been reported previously for a GHPR. The optimal pH for the reduction of phenylpyruvate to phenyllactate is pH 7. These data lend support to the idea of predicting enzymatic substrate specificity based on phylogenetic clustering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / isolation & purification
  • Alcohol Oxidoreductases / metabolism*
  • Amino Acid Sequence
  • Kinetics
  • Molecular Sequence Data
  • Phylogeny
  • Rhizobium etli / enzymology
  • Sequence Alignment
  • Substrate Specificity


  • Alcohol Oxidoreductases
  • glyoxylate reductase