Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 62, Issue 3, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202213053
Keywords
Antibiotics; Biosynthesis; P450 Enzymes; Polyketides; Structure Elucidation
Categories
Ask authors/readers for more resources
This study reveals the key epoxidation reaction in the synthesis of Abyssomicin C and the structure of the enzyme AbyV involved in this reaction. The combination of selective carbon-13 labeling with NMR spectroscopy proves to be an important tool in studying enzyme-catalyzed reactions in vitro.
Abyssomicin C and its atropisomer are potent inhibitors of bacterial folate metabolism. They possess complex polycyclic structures, and their biosynthesis has been shown to involve several unusual enzymatic transformations. Using a combination of synthesis and in vitro assays we reveal that AbyV, a cytochrome P450 enzyme from the aby gene cluster, catalyses a key late-stage epoxidation required for the installation of the characteristic ether-bridged core of abyssomicin C. The X-ray crystal structure of AbyV has been determined, which in combination with molecular dynamics simulations provides a structural framework for our functional data. This work demonstrates the power of combining selective carbon-13 labelling with NMR spectroscopy as a sensitive tool to interrogate enzyme-catalysed reactions in vitro with no need for purification.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available