TY - JOUR
T1 - Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis
AU - Bräuer, Alois
AU - Beck, Philipp
AU - Hintermann, Lukas
AU - Groll, Michael
N1 - 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.
PY - 2015/11/10
Y1 - 2015/11/10
N2 - © 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.
AB - © 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.
UR - http://hdl.handle.net/10754/599770
UR - http://doi.wiley.com/10.1002/anie.201507835
UR - http://www.scopus.com/inward/record.url?scp=84955194242&partnerID=8YFLogxK
U2 - 10.1002/anie.201507835
DO - 10.1002/anie.201507835
M3 - Article
C2 - 26553478
SN - 1433-7851
VL - 55
SP - 422
EP - 426
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
IS - 1
ER -