Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis
Type
ArticleKAUST Grant Number
1974-01Date
2015-11-10Online Publication Date
2015-11-10Print Publication Date
2016-01-04Permanent link to this record
http://hdl.handle.net/10754/599770
Metadata
Show full item recordAbstract
© 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.Citation
Bräuer 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.Sponsors
This 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.Publisher
WileyJournal
Angewandte ChemiePubMed ID
26553478ae974a485f413a2113503eed53cd6c53
10.1002/anie.201507835
Scopus Count
Collections
Publications Acknowledging KAUST SupportRelated articles
- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones.
- Authors: Einsiedler M, Jamieson CS, Maskeri MA, Houk KN, Gulder TAM
- Issue date: 2021 Apr 6
- 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
- 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 Jul
- 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
- Peroxy Intermediate Drives Carbon Bond Activation in the Dioxygenase AsqJ.
- Authors: Auman D, Ecker F, Mader SL, Dorst KM, Bräuer A, Widmalm G, Groll M, Kaila VRI
- Issue date: 2022 Aug 31