Alternative Reactivity of Leucine 5-Hydroxylase Using an Olefin-Containing Substrate to Construct a Substituted Piperidine Ring
- 13 May 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 59 (21), 1961-1965
- https://doi.org/10.1021/acs.biochem.0c00289
Abstract
Applying enzymatic reactions to produce useful molecules is a central focus of chemical biology. Iron and 2-oxoglutarate (Fe/2OG) enzymes are found in all kingdoms of life and catalyze a broad array of oxidative transformations. Herein, we demonstrate that the activity of an Fe/2OG enzyme can be redirected when changing the targeted carbon hybridization from sp3 to sp2. During leucine 5-hydroxylase catalysis, installation of an olefin group onto the substrate redirects the Fe(IV)-oxo species reactivity from hydroxylation to asymmetric epoxidation. The resulting epoxide subsequently undergoes intramolecular cyclization to form the substituted piperidine, 2S,5S-hydroxypipecolic acid.Keywords
Funding Information
- National Science Foundation (CHE-1845913)
- North Carolina State University
- Carnegie Mellon University
- U.S. Department of Health and Human Services (GM125924)
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