Oliver F Brandenberg1, Rudi Fasan2, Frances H Arnold3. 1. Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd, Pasadena, CA 91125, USA. 2. Department of Chemistry, University of Rochester, Hutchison Hall, 120 Trustee Rd, Rochester, NY 14627, USA. Electronic address: rfasan@ur.rochester.edu. 3. Division of Chemistry and Chemical Engineering, California Institute of Technology, 1200 East California Blvd, Pasadena, CA 91125, USA. Electronic address: frances@cheme.caltech.edu.
Abstract
The surge in reports of heme-dependent proteins as catalysts for abiotic, synthetically valuable carbene and nitrene transfer reactions dramatically illustrates the evolvability of the protein world and our nascent ability to exploit that for new enzyme chemistry. We highlight the latest additions to the hemoprotein-catalyzed reaction repertoire (including carbene Si-H and C-H insertions, Doyle-Kirmse reactions, aldehyde olefinations, azide-to-aldehyde conversions, and intermolecular nitrene C-H insertion) and show how different hemoprotein scaffolds offer varied reactivity and selectivity. Preparative-scale syntheses of pharmaceutically relevant compounds accomplished with these new catalysts are beginning to demonstrate their biotechnological relevance. Insights into the determinants of enzyme lifetime and product yield are providing generalizable cues for engineering heme-dependent proteins to further broaden the scope and utility of these non-natural activities.
The surge in reports of heme-dependent proteins as catalysts for abiotic, synthetically valuable n class="Chemical">carbene and nitrenetransfer reactions dramatically illustrates the evolvability of the protein world and our nascent ability to exploit that for new enzyme chemistry. We highlight the latest additions to the hemoprotein-catalyzed reaction repertoire (including carbeneSi-H and C-H insertions, Doyle-Kirmse reactions, aldehyde olefinations, azide-to-aldehydeconversions, and intermolecular nitrene C-H insertion) and show how different hemoprotein scaffolds offer varied reactivity and selectivity. Preparative-scale syntheses of pharmaceutically relevant compounds accomplished with these new catalysts are beginning to demonstrate their biotechnological relevance. Insights into the determinants of enzyme lifetime and product yield are providing generalizable cues for engineering heme-dependent proteins to further broaden the scope and utility of these non-natural activities.
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