Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis
KAUST Grant Number1974-01
Permanent link to this recordhttp://hdl.handle.net/10754/599770
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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.