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Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One‐Pot Multistep Quinolone Antibiotic Biosynthesis
Author(s) -
Bräuer Alois,
Beck Philipp,
Hintermann Lukas,
Groll Michael
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201507835
Subject(s) - dioxygenase , chemistry , biosynthesis , bicyclic molecule , stereochemistry , aspergillus nidulans , quinolone , enzyme , epoxide , combinatorial chemistry , biochemistry , antibiotics , catalysis , mutant , gene
Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The Fe II /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.