A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 06 2023
10 06 2023
Historique:
received:
02
09
2022
accepted:
25
05
2023
medline:
12
6
2023
pubmed:
11
6
2023
entrez:
10
6
2023
Statut:
epublish
Résumé
Oxepinone rings represent one of structurally unusual motifs of natural products and the biosynthesis of oxepinones is not fully understood. 1,5-Seco-vibralactone (3) features an oxepinone motif and is a stable metabolite isolated from mycelial cultures of the mushroom Boreostereum vibrans. Cyclization of 3 forms vibralactone (1) whose β-lactone-fused bicyclic core originates from 4-hydroxybenzoate, yet it remains elusive how 4-hydroxybenzoate is converted to 3 especially for the oxepinone ring construction in the biosynthesis of 1. In this work, using activity-guided fractionation together with proteomic analyses, we identify an NADPH/FAD-dependent monooxygenase VibO as the key enzyme performing a crucial ring-expansive oxygenation on the phenol ring to generate the oxepin-2-one structure of 3. The crystal structure of VibO reveals that it forms a dimeric phenol hydroxylase-like architecture featured with a unique substrate-binding pocket adjacent to the bound FAD. Computational modeling and solution studies provide insight into the likely VibO active site geometry, and suggest possible involvement of a flavin-C4a-OO(H) intermediate.
Identifiants
pubmed: 37301868
doi: 10.1038/s41467-023-39108-x
pii: 10.1038/s41467-023-39108-x
pmc: PMC10257657
doi:
Substances chimiques
vibralactone
0
4-hydroxybenzoic acid
JG8Z55Y12H
Mixed Function Oxygenases
EC 1.-
Lactones
0
Flavins
0
Flavin-Adenine Dinucleotide
146-14-5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3436Informations de copyright
© 2023. The Author(s).
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