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Publication type: Article in scientific journal
Type of review: Peer review (publication)
Title: Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols
Authors: Voss, Moritz
Küng, Robin
Hayashi, Takahiro
Jonczyk, Magdalena
Niklaus, Michael
Iding, Hans
Wetzl, Dennis
Buller, Rebecca
et. al: No
DOI: 10.1002/cctc.202001871
Published in: ChemCatChem
Volume(Issue): 13
Issue: 6
Pages: 1538
Pages to: 1545
Issue Date: Dec-2020
Publisher / Ed. Institution: Wiley
ISSN: 1867-3880
Language: English
Subjects: Biocatalysis; Ketoreductase; Substrate scope; Anti-Prelog stereoselectivity; Multi-factorial screening
Subject (DDC): 660.6: Biotechnology
Abstract: Enzymes are valuable tools to introduce chirality into small molecules. Especially, ketoreductase (KRED)‐catalyzed transformations of ketones to yield chiral secondary alcohols have become an established biocatalytic process step in the pharmaceutical and fine chemical industry. Development time, however, remains a critical factor in chemical process development and thus, the competitiveness of a biocatalytic reaction step is often governed by the availability of off‐the‐shelf enzyme libraries. To expand the biocatalytic toolbox with additional ketoreductases, we established a multi‐faceted screening procedure to capture KRED diversity from different sources, such as literature, available genome data, and uncharacterized microbial strains. Overall, we built a library consisting of 51 KRED enzymes, 29 of which have never been described in literature before. Notably, 18 of the newly described enzymes exhibited anti‐Prelog preference complementing the majority of ketoreductases which generally follow Prelog’s rule. Analysis of the library’s catalytic activity toward a chemically diverse ketone substrate set of pharmaceutical interest further highlighted the broad substrate scope and the complementing enantio‐preference of the individual KREDs. Using the generated sequence‐function data of the included short chain dehydrogenases in a bioinformatic analysis led to the identification of possible sequence determinants of the stereospecificity exhibited by these enzymes.
Further description: This is the peer reviewed version which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Fulltext version: Accepted version
License (according to publishing contract): Licence according to publishing contract
Restricted until: 2021-12-12
Departement: Life Sciences and Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Appears in collections:Publikationen Life Sciences und Facility Management

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