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https://doi.org/10.21256/zhaw-21381| Publikationstyp: | Beitrag in wissenschaftlicher Zeitschrift |
| Art der Begutachtung: | Peer review (Publikation) |
| Titel: | Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols |
| Autor/-in: | Voss, Moritz Küng, Robin Hayashi, Takahiro Jonczyk, Magdalena Niklaus, Michael Iding, Hans Wetzl, Dennis Buller, Rebecca |
| et. al: | No |
| DOI: | 10.1002/cctc.202001871 10.21256/zhaw-21381 |
| Erschienen in: | ChemCatChem |
| Band(Heft): | 13 |
| Heft: | 6 |
| Seite(n): | 1538 |
| Seiten bis: | 1545 |
| Erscheinungsdatum: | Dez-2020 |
| Verlag / Hrsg. Institution: | Wiley |
| ISSN: | 1867-3880 1867-3899 |
| Sprache: | Englisch |
| Schlagwörter: | Biocatalysis; Ketoreductase; Substrate scope; Anti-Prelog stereoselectivity; Multi-factorial screening |
| Fachgebiet (DDC): | 660.6: Biotechnologie |
| Zusammenfassung: | 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. |
| Weitere Angaben: | This is the peer reviewed version which has been published in final form at https://doi.org/10.1002/cctc.202001871. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/21381 |
| Volltext Version: | Akzeptierte Version |
| Lizenz (gemäss Verlagsvertrag): | Lizenz gemäss Verlagsvertrag |
| Gesperrt bis: | 2021-12-12 |
| Departement: | Life Sciences und Facility Management |
| Organisationseinheit: | Institut für Chemie und Biotechnologie (ICBT) |
| Enthalten in den Sammlungen: | Publikationen Life Sciences und Facility Management |
Dateien zu dieser Ressource:
| Datei | Beschreibung | Größe | Format | |
|---|---|---|---|---|
| 2020-Voss-etal_Multi-faceted-set-up-diverse-ketoreductase-library_cctc.pdf | Accepted Version | 1.23 MB | Adobe PDF |  Öffnen/Anzeigen |
Zur Langanzeige
Voss, M., Küng, R., Hayashi, T., Jonczyk, M., Niklaus, M., Iding, H., Wetzl, D., & Buller, R. (2020). Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols. ChemCatChem, 13(6), 1538–1545. https://doi.org/10.1002/cctc.202001871
Voss, M. et al. (2020) ‘Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols’, ChemCatChem, 13(6), pp. 1538–1545. Available at: https://doi.org/10.1002/cctc.202001871.
M. Voss et al., “Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols,” ChemCatChem, vol. 13, no. 6, pp. 1538–1545, Dec. 2020, doi: 10.1002/cctc.202001871.
VOSS, Moritz, Robin KÜNG, Takahiro HAYASHI, Magdalena JONCZYK, Michael NIKLAUS, Hans IDING, Dennis WETZL und Rebecca BULLER, 2020. Multi‐faceted set‐up of a diverse ketoreductase library enables the synthesis of pharmaceutically‐relevant secondary alcohols. ChemCatChem. Dezember 2020. Bd. 13, Nr. 6, S. 1538–1545. DOI 10.1002/cctc.202001871
Voss, Moritz, Robin Küng, Takahiro Hayashi, Magdalena Jonczyk, Michael Niklaus, Hans Iding, Dennis Wetzl, and Rebecca Buller. 2020. “Multi‐Faceted Set‐up of a Diverse Ketoreductase Library Enables the Synthesis of Pharmaceutically‐Relevant Secondary Alcohols.” ChemCatChem 13 (6): 1538–45. https://doi.org/10.1002/cctc.202001871.
Voss, Moritz, et al. “Multi‐Faceted Set‐up of a Diverse Ketoreductase Library Enables the Synthesis of Pharmaceutically‐Relevant Secondary Alcohols.” ChemCatChem, vol. 13, no. 6, Dec. 2020, pp. 1538–45, https://doi.org/10.1002/cctc.202001871.
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