A Peroxygenase‐Alcohol Dehydrogenase Cascade Reaction to Transform Ethylbenzene Derivatives into Enantioenriched Phenylethanols

• Published in: Chembiochem : a European journal of chemical biology Vol. 23; no. 6; pp. e202200017 - n/a
• Main Authors: Xu, Xiaomin, Brasselet, Hugo, Jongkind, Ewald P. J., Alcalde, Miguel, Paul, Caroline E., Hollmann, Frank
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 18-03-2022; John Wiley and Sons Inc
• Subjects: Alcohol dehydrogenase; Alcohol Dehydrogenase - metabolism; alcohol dehydrogenases; asymmetric reduction; Benzene Derivatives; bienzymatic cascades; Cascade chemical reactions; Dehydrogenase; Dehydrogenases; Enantiomers; Ethylbenzene; Intermediates; Kefir; Ketones; Mixed Function Oxygenases; Oxidation-Reduction; oxyfunctionalisation; peroxygenases; Phenylethyl Alcohol; Rhodococcus; Stereoisomerism; asymmetric reduction; bienzymatic cascades; oxyfunctionalisation; alcohol dehydrogenases; peroxygenases
• ISSN: 1439-4227; 1439-7633; 1439-7633
• DOI: 10.1002/cbic.202200017

In this study, we developed a new bienzymatic reaction to produce enantioenriched phenylethanols. In a first step, the recombinant, unspecific peroxygenase from Agrocybe aegerita (rAaeUPO) was used to oxidise ethylbenzene and its derivatives to the corresponding ketones (prochiral intermediates) followed by enantioselective reduction into the desired (R)‐ or (S)‐phenylethanols using the (R)‐selective alcohol dehydrogenase (ADH) from Lactobacillus kefir (LkADH) or the (S)‐selective ADH from Rhodococcus ruber (ADH‐A). In a one‐pot two‐step cascade, 11 ethylbenzene derivatives were converted into the corresponding chiral alcohols at acceptable yields and often excellent enantioselectivity.
A bienzymatic cascade to access complementary chiral phenylethanols from simple ethylbenzene derivatives is presented, combining peroxygenase‐catalysed oxyfunctionalisation to the corresponding acetophenone with alcohol dehydrogenase‐catalysed enantioselective reduction.