Biocatalytic One-Carbon Ring Expansion of Aziridines to Azetidines via a Highly Enantioselective [1,2]-Stevens Rearrangement
Abstract
We report enantioselective one-carbon ring expansion of aziridines to make azetidines as a new-to-nature activity of engineered "carbene transferase" enzymes. A laboratory-evolved variant of cytochrome P450_(BM3), P411-AzetS, not only exerts unparalleled stereocontrol (99:1 er) over a [1,2]-Stevens rearrangement but also overrides the inherent reactivity of aziridinium ylides, cheletropic extrusion of olefins, to perform a [1,2]-Stevens rearrangement. By controlling the fate of the highly reactive aziridinium ylide intermediates, these evolvable biocatalysts promote a transformation which cannot currently be performed using other catalyst classes.
Additional Information
© 2022 American Chemical Society. Received: January 8, 2022; Published: March 8, 2022. This research was sponsored by the U.S. Army Research Office and accomplished under contracts W911NF-19-D-0001 and W911NF-19-2-0026 for the Institute for Collaborative Biotechnologies. D.C.M. was supported by a Ruth Kirschstein NIH Postdoctoral Fellowship (F32GM128247). The authors wish to thank Dr. Sabine Brinkmann-Chen, Dr. Nathaniel Goldberg, and Dr. Nicholas Porter for assistance preparing the manuscript. The authors declare no competing financial interest.Attached Files
Accepted Version - nihms-1787244.pdf
Supplemental Material - ja2c00251_si_001.pdf
Supplemental Material - ja2c00251_si_002.xlsx
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Additional details
- PMCID
- PMC9022672
- Eprint ID
- 110345
- Resolver ID
- CaltechAUTHORS:20210821-140525422
- Army Research Office (ARO)
- W911NF-19-D-0001
- Army Research Office (ARO)
- W911NF-19-2-0026
- NIH Postdoctoral Fellowship
- F32GM128247
- Created
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2021-08-21Created from EPrint's datestamp field
- Updated
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2023-07-06Created from EPrint's last_modified field
- Caltech groups
- Division of Biology and Biological Engineering (BBE)