The Role of Cytochromeâ
P450 AbyV in the Final Stages of Abyssomicinâ
C Biosynthesis.
Angew Chem Int Ed Engl
; 62(3): e202213053, 2023 01 16.
Article
em En
| MEDLINE
| ID: mdl-36314667
Abyssomicinâ
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 cytochromeâ
P450 enzyme from the aby gene cluster, catalyses a key late-stage epoxidation required for the installation of the characteristic ether-bridged core of abyssomicinâ
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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Bicíclicos Heterocíclicos com Pontes
/
Sistema Enzimático do Citocromo P-450
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Ano de publicação:
2023
Tipo de documento:
Article
País de publicação:
Alemanha