Synthesis of Chiral Amines via a Bi-Enzymatic Cascade Using an Ene-Reductase and Amine Dehydrogenase

Ewald P.J. Jongkind, Aurélie Fossey-Jouenne, Ombeline Mayol, Anne Zaparucha, Carine Vergne-Vaxelaire, Caroline E. Paul*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review


Access to chiral amines with more than one stereocentre remains challenging, although an increasing number of methods are emerging. Here we developed a proof-of-concept bi-enzymatic cascade, consisting of an ene reductase and amine dehydrogenase (AmDH), to afford chiral diastereomerically enriched amines in one pot. The asymmetric reduction of unsaturated ketones and aldehydes by ene reductases from the Old Yellow Enzyme family (OYE) was adapted to reaction conditions for the reductive amination by amine dehydrogenases. By studying the substrate profiles of both reported biocatalysts, thirteen unsaturated carbonyl substrates were assayed against the best duo OYE/AmDH. Low (5 %) to high (97 %) conversion rates were obtained with enantiomeric and diastereomeric excess of up to 99 %. We expect our established bi-enzymatic cascade to allow access to chiral amines with both high enantiomeric and diastereomeric excess from varying alkene substrates depending on the combination of enzymes.

Original languageEnglish
Article numbere202101576
Number of pages9
Issue number2
Publication statusPublished - 2021

Bibliographical note

Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.


  • asymmetric reduction
  • biocascades
  • Biocatalysis
  • Old Yellow Enzymes
  • reductive amination


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