Cyclopropanation and aziridination catalyzed by non-heme iron and 2-oxoglutarate dependent enzymes.
| Autor: | Chen TY; Department of Chemistry, North Carolina State University, Raleigh, NC, United States., Cha L; Department of Chemistry, North Carolina State University, Raleigh, NC, United States., Paris JC; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA, United States., Guo Y; Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA, United States. Electronic address: ysguo@andrew.cmu.edu., Chang WC; Department of Chemistry, North Carolina State University, Raleigh, NC, United States. Electronic address: wchang6@ncsu.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Methods in enzymology [Methods Enzymol] 2024; Vol. 704, pp. 91-111. Date of Electronic Publication: 2024 Jun 29. |
| DOI: | 10.1016/bs.mie.2024.05.003 |
| Abstrakt: | Cyclopropane and azacyclopropane, also known as aziridine, moieties are found in natural products. These moieties serve as pivotal components that lead to a broad spectrum of biological activities. While diverse strategies involving various classes of enzymes are utilized to catalyze formation of these strained three-membered rings, how non-heme iron and 2-oxoglutarate (Fe/2OG) dependent enzymes enable regio- and stereo-selective C-C and C-N ring closure has only been reported very recently. Herein, we present detailed experimental protocols for mechanistically studying Fe/2OG enzymes that catalyze cyclopropanation and aziridination reactions. These protocols include protein purification, in vitro assays, biophysical spectroscopies, and isotope-tracer experiments. We also report how to use in silico approaches to look for Fe/2OG aziridinases. Furthermore, our current mechanistic understanding of three-membered ring formation is discussed. These results not only shed light on the reaction mechanisms of Fe/2OG enzymes-catalyzed cyclopropanation and aziridination, but also open avenues for expanding the reaction repertoire of the Fe/2OG enzyme superfamily. (Copyright © 2024. Published by Elsevier Inc.) |
| Databáze: | MEDLINE |
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