- Titel
- Structural and Mechanistic Studies on Substrate and Stereoselectivity of the Indole Monooxygenase VpIndA1
- Untertitel
- New Avenues for Biocatalytic Epoxidations and Sulfoxidations
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:15-qucosa2-977087
- Quellenangabe
- Angewandte Chemie
Erscheinungsjahr: 2023
Jahrgang: 62
Heft: 17
Seiten: 1-8
ISSN: 1433-7851
E-ISSN: 1521-3773 - Erstveröffentlichung
- 2023
- Abstract (EN)
- Flavoprotein monooxygenases are a versatile group of enzymes for biocatalytic transformations. Among these, group E monooxygenases (GEMs) catalyze enantioselective epoxidation and sulfoxidation reactions. Here, we describe the crystal structure of an indole monooxygenase from the bacterium Variovorax paradoxus EPS, a GEM designated as VpIndA1. Complex structures with substrates reveal productive binding modes that, in conjunction with force-field calculations and rapid mixing kinetics, reveal the structural basis of substrate and stereoselectivity. Structure-based redesign of the substrate cavity yielded variants with new substrate selectivity (for sulfoxidation of benzyl phenyl sulfide) or with greatly enhanced stereoselectivity (from 35.1% to 99.8% ee for production of (1S,2R)-indene oxide). This first determination of the substrate binding mode of GEMs combined with structure-function relationships opens the door for structure-based design of these powerful biocatalysts.
- Andere Ausgabe
- Link zur Erstveröffentlichung
DOI: 10.1002/anie.202300657 - Freie Schlagwörter (EN)
- Biocatalysis · Flavoenzyme · Monooxygenase · Protein Crystallography · Structure-Based Enzyme Design
- Klassifikation (DDC)
- 540
- Verlag
- Wiley-VCH, Weinheim
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:15-qucosa2-977087
- Veröffentlichungsdatum Qucosa
- 27.06.2025
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY 4.0