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A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone

Author

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  • Ke-Na Feng

    (Chinese Academy of Sciences)

  • Yue Zhang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Mingfang Zhang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Yan-Long Yang

    (Chinese Academy of Sciences
    Lanzhou University)

  • Ji-Kai Liu

    (South-Central Minzu University)

  • Lifeng Pan

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Ying Zeng

    (Chinese Academy of Sciences)

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.

Suggested Citation

  • Ke-Na Feng & Yue Zhang & Mingfang Zhang & Yan-Long Yang & Ji-Kai Liu & Lifeng Pan & Ying Zeng, 2023. "A flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39108-x
    DOI: 10.1038/s41467-023-39108-x
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    References listed on IDEAS

    as
    1. Robin Teufel & Akimasa Miyanaga & Quentin Michaudel & Frederick Stull & Gordon Louie & Joseph P. Noel & Phil S. Baran & Bruce Palfey & Bradley S. Moore, 2013. "Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement," Nature, Nature, vol. 503(7477), pages 552-556, November.
    2. Pamela P. Peralta-Yahya & Mario Ouellet & Rossana Chan & Aindrila Mukhopadhyay & Jay D. Keasling & Taek Soon Lee, 2011. "Identification and microbial production of a terpene-based advanced biofuel," Nature Communications, Nature, vol. 2(1), pages 1-8, September.
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