Biosynthetic Elucidation and Structural Revision of Brevioneâ
E: Characterization of the Key Dioxygenase for Pathway Branching from Setosusin Biosynthesis.
Angew Chem Int Ed Engl
; 61(48): e202210938, 2022 11 25.
Article
en En
| MEDLINE
| ID: mdl-36196912
ABSTRACT
Brevioneâ
E (1) is a fungal hexacyclic meroditerpenoid with unique oxepane and cycloheptenone moieties. In this study, we identified the biosynthetic gene cluster of 1 and elucidated its biosynthetic pathway via heterologous expression of the biosynthetic genes and in vitro enzymatic reactions. Surprisingly, reexamination of the structure of 1 revealed a substituted tetrahydrofuran ring instead of the previously proposed oxepane system. Moreover, we determined that cycloheptenone synthesis involves skeletal rearrangement catalyzed by the α-ketoglutarate-dependent dioxygenase BrvJ. BrvJ is highly homologous to SetK, which engages in the biosynthesis of another fungal metabolite, setosusin, and accepts the same substrate as BrvJ but performs only simple hydroxylation. Finally, we identified the key amino acid residues critical for product selectivity of BrvJ and SetK, providing insight into how the biosynthesis pathways of 1 and setosusin diverge and how fungi diversify natural products.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Productos Biológicos
/
Dioxigenasas
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2022
Tipo del documento:
Article
País de afiliación:
China