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

Alois Bräuer, Philipp Beck, Lukas Hintermann, Michael Groll

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

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.
Original languageEnglish (US)
Pages (from-to)422-426
Number of pages5
JournalAngewandte Chemie International Edition
Volume55
Issue number1
DOIs
StatePublished - Nov 10 2015
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): 1974-01
Acknowledgements: 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.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.

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