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https://doi.org/10.21256/zhaw-26366| Publikationstyp: | Beitrag in wissenschaftlicher Zeitschrift |
| Art der Begutachtung: | Peer review (Publikation) |
| Titel: | Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5* |
| Autor/-in: | Voss, Moritz Hüppi, Sean Schaub, Daniela Hayashi, Takahiro Ligibel, Mathieu Sager, Emine Schroer, Kirsten Snajdrova, Radka Buller, Rebecca |
| et. al: | No |
| DOI: | 10.1002/cctc.202201115 10.21256/zhaw-26366 |
| Erschienen in: | ChemCatChem |
| Band(Heft): | 14 |
| Heft: | 24 |
| Seite(n): | e202201115 |
| Erscheinungsdatum: | 2022 |
| Verlag / Hrsg. Institution: | Wiley |
| ISSN: | 1867-3880 1867-3899 |
| Sprache: | Englisch |
| Schlagwörter: | Biocatalysis; Enzyme engineering |
| Fachgebiet (DDC): | 660.6: Biotechnologie |
| Zusammenfassung: | Enzymatic late-stage diversification of small molecules has the potential to rapidly generate diversity in compound libraries dedicated to drug discovery. In this context, freestanding Fe(II)/α-ketoglutarate-dependent halogenases have raised particular interest as this enzyme family allows the otherwise difficult regio- and stereoselective halogenation of unactivated C(sp3)-H bonds. Here, we report the development of two engineered variants of the halogenase WelO5* for the racemic resolution of a mixture of stereoisomers generated in the synthesis of a bioactive martinelline-derived fragment. By screening a 3-site combinatorial variant library, we could identify two variants exhibiting exquisite substrate selectivity towards the desired enantiomers. Strikingly, the inversion of substrate stereopreference between the halogenase variants was achieved by varying only three residues in the active site. Protein crystallization and subsequent structure elucidation of the wildtype enzyme and a WelO5* variant shed light on the factors governing substrate acceptance and selectivity. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/26366 |
| Volltext Version: | Publizierte Version |
| Lizenz (gemäss Verlagsvertrag): | CC BY 4.0: Namensnennung 4.0 International |
| 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 | |
|---|---|---|---|---|
| 2022_Voss-etal_Enzyme-engineering-substrate-stereopreference-inversion-halogenase-WelO5.pdf | 1.84 MB | Adobe PDF |  Öffnen/Anzeigen |
Zur Langanzeige
Voss, M., Hüppi, S., Schaub, D., Hayashi, T., Ligibel, M., Sager, E., Schroer, K., Snajdrova, R., & Buller, R. (2022). Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*. ChemCatChem, 14(24), e202201115. https://doi.org/10.1002/cctc.202201115
Voss, M. et al. (2022) ‘Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*’, ChemCatChem, 14(24), p. e202201115. Available at: https://doi.org/10.1002/cctc.202201115.
M. Voss et al., “Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*,” ChemCatChem, vol. 14, no. 24, p. e202201115, 2022, doi: 10.1002/cctc.202201115.
VOSS, Moritz, Sean HÜPPI, Daniela SCHAUB, Takahiro HAYASHI, Mathieu LIGIBEL, Emine SAGER, Kirsten SCHROER, Radka SNAJDROVA und Rebecca BULLER, 2022. Enzyme engineering enables inversion of substrate stereopreference of the halogenase WelO5*. ChemCatChem. 2022. Bd. 14, Nr. 24, S. e202201115. DOI 10.1002/cctc.202201115
Voss, Moritz, Sean Hüppi, Daniela Schaub, Takahiro Hayashi, Mathieu Ligibel, Emine Sager, Kirsten Schroer, Radka Snajdrova, and Rebecca Buller. 2022. “Enzyme Engineering Enables Inversion of Substrate Stereopreference of the Halogenase WelO5*.” ChemCatChem 14 (24): e202201115. https://doi.org/10.1002/cctc.202201115.
Voss, Moritz, et al. “Enzyme Engineering Enables Inversion of Substrate Stereopreference of the Halogenase WelO5*.” ChemCatChem, vol. 14, no. 24, 2022, p. e202201115, https://doi.org/10.1002/cctc.202201115.
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