Structural insights into the ene-­‐reductase synthesis of Profens

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • John Waller
  • Helen Toogood
  • Vijaykumar Karuppiah
  • Nicholas Rattray
  • David Mansell
  • Anna Fryszkowska
  • S.T Ahmed
  • R Bandichhor
  • G.P Reddy


Reduction of double bonds of α,β-­‐unsaturated carboxylic acids and esters by ene-­‐reductases remains challenging and it typically requires activation by a second electron-­‐withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-­‐arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-­‐crystal structural analysis of profen-­‐bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-­‐profens was established
and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-­‐active (S)-­‐profens.

Bibliographical metadata

Original languageEnglish
JournalOrganic and Biomolecular Chemistry
Early online date28 Apr 2017
Publication statusPublished - 2017

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