Stereo-electronic control of reaction selectivity in short-chain dehydrogenases: Decarboxylation, epimerization, and dehydration

Annika Jasmin Eveliina Borg, Martin Pfeiffer, Koen Beerens, Tom Desmet, Bernd Nidetzky*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Sugar nucleotide–modifying enzymes of the short-chain dehydrogenase/reductase type use transient oxidation–reduction by a tightly bound nicotinamide cofactor as a common strategy of catalysis to promote a diverse set of reactions, including decarboxylation, single- or double-site epimerization, and dehydration. Although the basic mechanistic principles have been worked out decades ago, the finely tuned control of reactivity and selectivity in several of these enzymes remains enigmatic. Recent evidence on uridine 5'-diphosphate (UDP)-glucuronic acid decarboxylases (UDP-xylose synthase, UDP-apiose/UDP-xylose synthase) and UDP-glucuronic acid-4-epimerase suggests that stereo-electronic constraints established at the enzyme's active site control the selectivity, and the timing of the catalytic reaction steps, in the conversion of the common substrate toward different products. The mechanistic idea of stereo-electronic control is extended to epimerases and dehydratases that deprotonate the Cα of the transient keto-hexose intermediate. The human guanosine 5'-diphosphate (GDP)-mannose 4,6-dehydratase was recently shown to use a minimal catalytic machinery, exactly as predicted earlier from theoretical considerations, for the β-elimination of water from the keto-hexose species.

Original languageEnglish
Pages (from-to)43-52
Number of pages10
JournalCurrent Opinion in Chemical Biology
Publication statusPublished - Apr 2021


  • Decarboxylase
  • Dehydratase
  • Epimerase
  • SDR
  • Short-chain dehydrogenase/reductase
  • Stereo-electronic effect
  • Transient oxidation-reduction

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry


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