Browse by author
Lookup NU author(s): Dr James StachORCiD, Professor Paul RaceORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.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.
Author(s): Devine AJ, Parnell AE, Back CR, Lees NR, Johns ST, Zulkepli AZ, Barringer R, Zorn K, Stach JEM, Crump MP, Hayes MA, van der Kamp MW, Race PR, Willis CL
Publication type: Article
Publication status: Published
Journal: Angewandte Chemie - International Edition
Year: 2023
Volume: 62
Issue: 3
Print publication date: 16/01/2023
Online publication date: 31/10/2022
Acceptance date: 05/09/2022
Date deposited: 29/06/2023
ISSN (print): 1433-7851
ISSN (electronic): 1521-3773
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/anie.202213053
DOI: 10.1002/anie.202213053
Altmetrics provided by Altmetric