The Role of Cytochrome P450 AbyV in the Final Stages of Abyssomicin C Biosynthesis.
Antibiotics
Biosynthesis
P450 Enzymes
Polyketides
Structure Elucidation
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
16 01 2023
16 01 2023
Historique:
received:
05
09
2022
pubmed:
1
11
2022
medline:
12
1
2023
entrez:
31
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36314667
doi: 10.1002/anie.202213053
pmc: PMC10107801
doi:
Substances chimiques
abyssomicin C
0
Cytochrome P-450 Enzyme System
9035-51-2
Bridged Bicyclo Compounds, Heterocyclic
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202213053Subventions
Organisme : Engineering and Physical Sciences Research Council
ID : EP/G036764/1
Organisme : Engineering and Physical Sciences Research Council
ID : EP/L016494/1
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L01386X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T001968/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M012107/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/T008741/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/M026280/1
Pays : United Kingdom
Informations de copyright
© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.
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