Directed Evolution of Nonheme Iron Enzymes for Enantioselective Aminative Difunctionalization of Alkenes
The direct aminative difunctionalization of alkenes offers a powerful strategy for synthesizing valuable amine-containing compounds. However, achieving this transformation enantioselectively remains a significant challenge in both synthetic chemistry and biocatalysis. In this study, we engineered a nonheme iron enzyme, quercetin 2,3-dioxygenase from <i>Bacillus subtilis</i> (<i>Bs</i>QueD), to catalyze three distinct alkene aminofunctionalization reactions with high efficiency and enantiocontrol. Through directed evolution, we developed an optimized <i>Bs</i>QueD variant capable of producing a wide array of chiral 2-azidoamines, 2-aminothiazolines, and 2-aminooxazolines with up to 72% yield and 99:1 enantiomeric ratio (e.r.). Mechanistic investigations suggest a stepwise radical addition pathway. This work broadens the scope of biocatalytic alkene difunctionalization, providing a sustainable and efficient route for synthesizing diverse chiral primary amines.
Authors
- S F. Li (ORCID: https://orcid.org/0009-0001-4847-7153)
- Jiahua Luo (ORCID: https://orcid.org/0000-0002-7911-5841)
- Xin Wang (ORCID: https://orcid.org/0000-0003-2968-2634)
- Zhi‐Jun Jia (ORCID: https://orcid.org/0000-0002-5143-4875)
- Li Ye (ORCID: https://orcid.org/0000-0001-5303-2549)
- Fei Liu (ORCID: https://orcid.org/0000-0002-0310-1072)
- Chun Zhang (ORCID: https://orcid.org/0000-0002-4646-1879)
- Xue Zeng (ORCID: https://orcid.org/0000-0001-6433-2272)
- Wei Long (ORCID: https://orcid.org/0000-0002-5365-9111)
- Peng Chen (ORCID: https://orcid.org/0009-0005-7249-8180)
- Yongxiang Zheng (ORCID: https://orcid.org/0000-0002-9068-5765)
- Zhonghang Fan (ORCID: https://orcid.org/0000-0002-4621-5379)
- Jiayao Li (ORCID: https://orcid.org/0009-0002-5947-692X)
Institutions
- Sichuan University (CN)
- International Drug Development (FR)
Publication Details
- Journal
- JACS Au
- Published
- 2025-08-27
- DOI
- https://doi.org/10.1021/jacsau.5c00817
- Citations
- 4
- Primary Topic
- Synthesis and Catalytic Reactions
- Type
- article
- Field-Weighted Citation Impact
- 3.74
Funders
- China Postdoctoral Science Foundation
- Sichuan University
- National Key Research and Development Program of China