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http://dx.doi.org/10.18419/opus-13596
Autor(en): | Schneider, Andreas Curado, Christian Lystbaek, Thomas B. Osuna, Sílvia Hauer, Bernhard |
Titel: | Harnessing the structure and dynamics of the squalene‐hopene cyclase for (-)‐ambroxide production |
Erscheinungsdatum: | 2023 |
Dokumentart: | Zeitschriftenartikel |
Seiten: | 10 |
Erschienen in: | Angewandte Chemie international edition 62 (2023), No. e202301607 |
URI: | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-136152 http://elib.uni-stuttgart.de/handle/11682/13615 http://dx.doi.org/10.18419/opus-13596 |
ISSN: | 1433-7851 1521-3773 |
Zusammenfassung: | Terpene cyclases offer enormous synthetic potential, given their unique ability to forge complex hydrocarbon scaffolds from achiral precursors within a single cationic rearrangement cascade. Harnessing their synthetic power, however, has proved to be challenging owing to their generally low catalytic performance. In this study, we unveiled the catalytic potential of the squalene‐hopene cyclase (SHC) by harnessing its structure and dynamics. First, we synergistically tailored the active site and entrance tunnel of the enzyme to generate a 397‐fold improved (-)‐ambroxide synthase. Our computational investigations explain how the introduced mutations work in concert to improve substrate acquisition, flow, and chaperoning. Kinetics, however, showed terpene‐induced inactivation of the membrane‐bound SHC to be the major turnover limitation in vivo. Merging this insight with the improved and stereoselective catalysis of the enzyme, we applied a feeding strategy to exceed 10 5 total turnovers. We believe that our results may bridge the gap for broader application of SHCs in synthetic chemistry. |
Enthalten in den Sammlungen: | 03 Fakultät Chemie |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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ANIE_ANIE202301607.pdf | 6,86 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons