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The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis

Lookup NU author(s): Dr James StachORCiD, Professor Paul RaceORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 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.

Publication metadata

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

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