Biocatalytic enantioselective formation and ring-opening of oxetanes
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 developi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56463-z |
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| author | Xia Hua Yuan-Fei Wang Xiao Jin Hong-Yin Yu Hui-Hui Wang Yong-Zheng Chen Nan-Wei Wan |
| author_facet | Xia Hua Yuan-Fei Wang Xiao Jin Hong-Yin Yu Hui-Hui Wang Yong-Zheng Chen Nan-Wei Wan |
| author_sort | Xia Hua |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e2bf9571d1e04524a6504a162dbc3094 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e2bf9571d1e04524a6504a162dbc30942025-02-02T12:33:18ZengNature PortfolioNature Communications2041-17232025-01-0116111210.1038/s41467-025-56463-zBiocatalytic enantioselective formation and ring-opening of oxetanesXia Hua0Yuan-Fei Wang1Xiao Jin2Hong-Yin Yu3Hui-Hui Wang4Yong-Zheng Chen5Nan-Wei Wan6School of Pharmacy, Zunyi Medical UniversitySchool of Pharmacy, Zunyi Medical UniversitySchool of Pharmacy, Zunyi Medical UniversitySchool of Pharmacy, Zunyi Medical UniversitySchool of Pharmacy, Zunyi Medical UniversitySchool of Pharmacy, Zunyi Medical UniversitySchool of Pharmacy, Zunyi Medical UniversityAbstract 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.https://doi.org/10.1038/s41467-025-56463-z |
| spellingShingle | Xia Hua Yuan-Fei Wang Xiao Jin Hong-Yin Yu Hui-Hui Wang Yong-Zheng Chen Nan-Wei Wan Biocatalytic enantioselective formation and ring-opening of oxetanes Nature Communications |
| title | Biocatalytic enantioselective formation and ring-opening of oxetanes |
| title_full | Biocatalytic enantioselective formation and ring-opening of oxetanes |
| title_fullStr | Biocatalytic enantioselective formation and ring-opening of oxetanes |
| title_full_unstemmed | Biocatalytic enantioselective formation and ring-opening of oxetanes |
| title_short | Biocatalytic enantioselective formation and ring-opening of oxetanes |
| title_sort | biocatalytic enantioselective formation and ring opening of oxetanes |
| url | https://doi.org/10.1038/s41467-025-56463-z |
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