The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis
| Autor: | Andrew J. Devine, Alice E. Parnell, Catherine R. Back, Nicholas R. Lees, Samuel T. Johns, Ainul Z. Zulkepli, Rob Barringer, Katja Zorn, James E. M. Stach, Matthew P. Crump, Martin A. Hayes, Marc W. van der Kamp, Paul R. Race, Christine L. Willis |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Angewandte Chemie. 135 |
| ISSN: | 1521-3757 0044-8249 |
| DOI: | 10.1002/ange.202213053 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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