Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis
KAUST Grant Number1974-01
MetadataShow full item record
Abstract© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.
CitationBräuer A, Beck P, Hintermann L, Groll M (2015) Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis. Angew Chem Int Ed 55: 422–426. Available: http://dx.doi.org/10.1002/anie.201507835.
SponsorsThis work was supported by the 1974-01 TUM-KAUST agreement on selective C[BOND]H bond activation (A.B.) and SFB749 (M.G.). We thank the staff of the beamline X06SA at the Paul Scherrer Institute, SLS, Villigen (Switzerland) for assistance during data collection.
CollectionsPublications Acknowledging KAUST Support
- Non-heme dioxygenase catalyzes atypical oxidations of 6,7-bicyclic systems to form the 6,6-quinolone core of viridicatin-type fungal alkaloids.
- Authors: Ishikawa N, Tanaka H, Koyama F, Noguchi H, Wang CC, Hotta K, Watanabe K
- Issue date: 2014 Nov 17
- Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ.
- Authors: Mader SL, Bräuer A, Groll M, Kaila VRI
- Issue date: 2018 Mar 21
- On how the binding cavity of AsqJ dioxygenase controls the desaturation reaction regioselectivity: a QM/MM study.
- Authors: Wojdyla Z, Borowski T
- Issue date: 2018 Jun 6
- Mechanistic insights into dioxygen activation, oxygen atom exchange and substrate epoxidation by AsqJ dioxygenase from quantum mechanical/molecular mechanical calculations.
- Authors: Song X, Lu J, Lai W
- Issue date: 2017 Aug 2
- Enzyme-catalyzed cationic epoxide rearrangements in quinolone alkaloid biosynthesis.
- Authors: Zou Y, Garcia-Borràs M, Tang MC, Hirayama Y, Li DH, Li L, Watanabe K, Houk KN, Tang Y
- Issue date: 2017 Mar