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Biocatalytic enantioselective formation and ring-opening of oxetanes

Author

Listed:
  • Xia Hua

    (Zunyi Medical University)

  • Yuan-Fei Wang

    (Zunyi Medical University)

  • Xiao Jin

    (Zunyi Medical University)

  • Hong-Yin Yu

    (Zunyi Medical University)

  • Hui-Hui Wang

    (Zunyi Medical University)

  • Yong-Zheng Chen

    (Zunyi Medical University)

  • Nan-Wei Wan

    (Zunyi Medical University)

Abstract

Although biocatalysis offers complementary or alternative approaches to traditional synthetic methods, the limited range of available enzymatic reactions currently poses challenges in synthesizing a diverse array of desired compounds. Consequently, there is a significant demand for developing novel biocatalytic processes to enable reactions that were previously unattainable. Herein, we report the discovery and subsequent protein engineering of a unique halohydrin dehalogenase to develop a biocatalytic platform for enantioselective formation and ring-opening of oxetanes. This biocatalytic platform, exhibiting high efficiency, excellent enantioselectivity, and broad scopes, facilitates the preparative-scale synthesis of chiral oxetanes and a variety of chiral γ-substituted alcohols. Additionally, both the enantioselective oxetane formation and ring-opening processes are proven scalable for large-scale transformations at high substrate concentrations, and can be integrated efficiently in a one-pot, one-catalyst cascade system. This work expands the enzymatic toolbox for non-natural reactions and will promote further exploration of the catalytic repertoire of halohydrin dehalogenases in synthetic and pharmaceutical chemistry.

Suggested Citation

  • Xia Hua & Yuan-Fei Wang & Xiao Jin & Hong-Yin Yu & Hui-Hui Wang & Yong-Zheng Chen & Nan-Wei Wan, 2025. "Biocatalytic enantioselective formation and ring-opening of oxetanes," Nature Communications, Nature, vol. 16(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56463-z
    DOI: 10.1038/s41467-025-56463-z
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    References listed on IDEAS

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    1. Christoph Fornacon-Wood & Bhargav R. Manjunatha & Merlin R. Stühler & Cesare Gallizioli & Carsten Müller & Patrick Pröhm & Alex J. Plajer, 2023. "Precise cooperative sulfur placement leads to semi-crystallinity and selective depolymerisability in CS2/oxetane copolymers," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Michael Winn & Michael Rowlinson & Fanghua Wang & Luis Bering & Daniel Francis & Colin Levy & Jason Micklefield, 2021. "Discovery, characterization and engineering of ligases for amide synthesis," Nature, Nature, vol. 593(7859), pages 391-398, May.
    3. Lara E. Zetzsche & Jessica A. Yazarians & Suman Chakrabarty & Meagan E. Hinze & Lauren A. M. Murray & April L. Lukowski & Leo A. Joyce & Alison R. H. Narayan, 2022. "Biocatalytic oxidative cross-coupling reactions for biaryl bond formation," Nature, Nature, vol. 603(7899), pages 79-85, March.
    4. Thomas W. Thorpe & James R. Marshall & Vanessa Harawa & Rebecca E. Ruscoe & Anibal Cuetos & James D. Finnigan & Antonio Angelastro & Rachel S. Heath & Fabio Parmeggiani & Simon J. Charnock & Roger M. , 2022. "Multifunctional biocatalyst for conjugate reduction and reductive amination," Nature, Nature, vol. 604(7904), pages 86-91, April.
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