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- Title
Biocatalytic characterization of an alcohol dehydrogenase variant deduced from Lactobacillus kefir in asymmetric hydrogen transfer.
- Authors
Rudzka, Aleksandra; Zdun, Beata; Antos, Natalia; Montero, Lia Martínez; Reiter, Tamara; Kroutil, Wolfgang; Borowiecki, Paweł
- Abstract
Hydrogen transfer biocatalysts to prepare optically pure alcohols are in need, especially when it comes to sterically demanding ketones, whereof the bioreduced products are either essential precursors of pharmaceutically relevant compounds or constitute APIs themselves. In this study, we report on the biocatalytic potential of an anti-Prelog (R)-specific Lactobacillus kefir ADH variant (Lk-ADH-E145F-F147L-Y190C, named Lk-ADH Prince) employed as E. coli/ADH whole-cell biocatalyst and its characterization for stereoselective reduction of prochiral carbonyl substrates. Key enzymatic reaction parameters, including the reaction medium, evaluation of cofactor-dependency, organic co-solvent tolerance, and substrate loading, were determined employing the drug pentoxifylline as a model prochiral ketone. Furthermore, to tap the substrate scope of Lk-ADH Prince in hydrogen transfer reactions, a broad range of 34 carbonylic derivatives was screened. Our data demonstrate that E. coli/Lk-ADH Prince exhibits activity toward a variety of structurally different ketones, furnishing optically active alcohol products at the high conversion of 65–99.9% and in moderate-to-high isolated yields (38–91%) with excellent anti-Prelog (R)-stereoselectivity (up to >99% ee) at substrate concentrations up to 100 mM. Alcohol dehydrogenases (ADH) are known to be efficient and stereoselective biocatalysts for reducing prochiral carbonyl compounds to chiral alcohols; however, their catalytic performances remain limited for application. Here, the authors demonstrate the wide substrate scope of a L. kefir ADH variant with anti-Prelog specificity to generate (R)-alcohols.
- Subjects
ALCOHOL dehydrogenase; HYDROGEN transfer reactions; KEFIR; ESCHERICHIA coli; LACTOBACILLUS; ALCOHOL
- Publication
Communications Chemistry, 2023, Vol 6, Issue 1, p1
- ISSN
2399-3669
- Publication type
Article
- DOI
10.1038/s42004-023-01013-1