7YJ0

Structural basis of oxepinone formation by a flavin-monooxygenase VibO

Summary for 7YJ0

• Entry DOI: 10.2210/pdb7yj0/pdb
• Descriptor: VibO, FLAVIN-ADENINE DINUCLEOTIDE, GLYCEROL, ... (4 entities in total)
• Functional Keywords: monooxygenase, ring-expansive oxygenation, oxidoreductase
• Biological source: Boreostereum vibrans
• Total number of polymer chains: 4
• Total formula weight: 290494.79

Authors

Zhang, M.F.,Pan, L.F. (deposition date: 2022-07-18, release date: 2023-05-10, Last modification date: 2024-05-08)

Primary citation

Feng, K.N.,Zhang, Y.,Zhang, M.,Yang, Y.L.,Liu, J.K.,Pan, L.,Zeng, Y.
A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone.
Nat Commun, 14:3436-3436, 2023

PubMed Abstract: 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.

PubMed: 37301868
DOI: 10.1038/s41467-023-39108-x

Experimental method

X-RAY DIFFRACTION (2.43 Å)