Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

Handle URI:
http://hdl.handle.net/10754/599770
Title:
Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis
Authors:
Bräuer, Alois; Beck, Philipp; Hintermann, Lukas; Groll, Michael
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.
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.
Publisher:
Wiley-Blackwell
Journal:
Angewandte Chemie International Edition
KAUST Grant Number:
1974-01
Issue Date:
10-Nov-2015
DOI:
10.1002/anie.201507835
PubMed ID:
26553478
Type:
Article
ISSN:
1433-7851
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.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorBräuer, Aloisen
dc.contributor.authorBeck, Philippen
dc.contributor.authorHintermann, Lukasen
dc.contributor.authorGroll, Michaelen
dc.date.accessioned2016-02-28T06:09:24Zen
dc.date.available2016-02-28T06:09:24Zen
dc.date.issued2015-11-10en
dc.identifier.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.en
dc.identifier.issn1433-7851en
dc.identifier.pmid26553478en
dc.identifier.doi10.1002/anie.201507835en
dc.identifier.urihttp://hdl.handle.net/10754/599770en
dc.description.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.en
dc.description.sponsorshipThis 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.en
dc.publisherWiley-Blackwellen
dc.subject4′-methoxyviridicatinen
dc.subjectalkaloidsen
dc.subjectAsqJ dioxygenaseen
dc.subjectbiosynthesisen
dc.subjectC-H activationen
dc.titleStructure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesisen
dc.typeArticleen
dc.identifier.journalAngewandte Chemie International Editionen
dc.contributor.institutionTechnische Universitat Munchen, Munich, Germanyen
kaust.grant.number1974-01en
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