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https://doi.org/10.21256/zhaw-23998| Publikationstyp: | Beitrag in wissenschaftlicher Zeitschrift |
| Art der Begutachtung: | Peer review (Publikation) |
| Titel: | Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens |
| Autor/-in: | Büchler, Johannes Malca, Sumire Honda Patsch, David Voss, Moritz Turner, Nicholas J. Bornscheuer, Uwe T. Allemann, Oliver Le Chapelain, Camille Lumbroso, Alexandre Loiseleur, Olivier Buller, Rebecca |
| et. al: | No |
| DOI: | 10.1038/s41467-022-27999-1 10.21256/zhaw-23998 |
| Erschienen in: | Nature Communications |
| Band(Heft): | 13 |
| Heft: | 371 |
| Erscheinungsdatum: | 18-Jan-2022 |
| Verlag / Hrsg. Institution: | Nature Publishing Group |
| ISSN: | 2041-1723 |
| Sprache: | Englisch |
| Fachgebiet (DDC): | 660.6: Biotechnologie |
| Zusammenfassung: | Late-stage functionalization of natural products offers an elegant route to create novel entities in a relevant biological target space. In this context, enzymes capable of halogenating sp3 carbons with high stereo- and regiocontrol under benign conditions have attracted particular attention. Enabled by a combination of smart library design and machine learning, we engineer the iron/α-ketoglutarate dependent halogenase WelO5* for the late-stage functionalization of the complex and chemically difficult to derivatize macrolides soraphen A and C, potent anti-fungal agents. While the wild type enzyme WelO5* does not accept the macrolide substrates, our engineering strategy leads to active halogenase variants and improves upon their apparent kcat and total turnover number by more than 90-fold and 300-fold, respectively. Notably, our machine-learning guided engineering approach is capable of predicting more active variants and allows us to switch the regio-selectivity of the halogenases facilitating the targeted analysis of the derivatized macrolides’ structure-function activity in biological assays. |
| URI: | https://digitalcollection.zhaw.ch/handle/11475/23998 |
| 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) |
| Publiziert im Rahmen des ZHAW-Projekts: | PgB P-14 Engineered Halogenases NCCR Catalysis |
| Enthalten in den Sammlungen: | Publikationen Life Sciences und Facility Management |
Dateien zu dieser Ressource:
| Datei | Beschreibung | Größe | Format | |
|---|---|---|---|---|
| 2022_Buechler-etal_Algorithm-aided-engineering-aliphatic-halogenase-WelO5.pdf | 2.3 MB | Adobe PDF |  Öffnen/Anzeigen |
Zur Langanzeige
Büchler, J., Malca, S. H., Patsch, D., Voss, M., Turner, N. J., Bornscheuer, U. T., Allemann, O., Le Chapelain, C., Lumbroso, A., Loiseleur, O., & Buller, R. (2022). Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens. Nature Communications, 13(371). https://doi.org/10.1038/s41467-022-27999-1
Büchler, J. et al. (2022) ‘Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens’, Nature Communications, 13(371). Available at: https://doi.org/10.1038/s41467-022-27999-1.
J. Büchler et al., “Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens,” Nature Communications, vol. 13, no. 371, Jan. 2022, doi: 10.1038/s41467-022-27999-1.
BÜCHLER, Johannes, Sumire Honda MALCA, David PATSCH, Moritz VOSS, Nicholas J. TURNER, Uwe T. BORNSCHEUER, Oliver ALLEMANN, Camille LE CHAPELAIN, Alexandre LUMBROSO, Olivier LOISELEUR und Rebecca BULLER, 2022. Algorithm-aided engineering of aliphatic halogenase WelO5* for the asymmetric late-stage functionalization of soraphens. Nature Communications. 18 Januar 2022. Bd. 13, Nr. 371. DOI 10.1038/s41467-022-27999-1
Büchler, Johannes, Sumire Honda Malca, David Patsch, Moritz Voss, Nicholas J. Turner, Uwe T. Bornscheuer, Oliver Allemann, et al. 2022. “Algorithm-Aided Engineering of Aliphatic Halogenase WelO5* for the Asymmetric Late-Stage Functionalization of Soraphens.” Nature Communications 13 (371). https://doi.org/10.1038/s41467-022-27999-1.
Büchler, Johannes, et al. “Algorithm-Aided Engineering of Aliphatic Halogenase WelO5* for the Asymmetric Late-Stage Functionalization of Soraphens.” Nature Communications, vol. 13, no. 371, Jan. 2022, https://doi.org/10.1038/s41467-022-27999-1.
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