Probing ferryl reactivity in a nonheme iron oxygenase using an expanded genetic code

Hardy, Florence J., Quesne, Matthew G., Gérard, Emilie F., Zhao, Jingming, Ortmayer, Mary, Taylor, Christopher J., Ali, Hafiz S., Slater, Jeffrey W., Levy, Colin W., Heyes, Derren J., Bollinger, J. Martin, de Visser, Sam P. and Green, Anthony P. 2024. Probing ferryl reactivity in a nonheme iron oxygenase using an expanded genetic code. ACS Catalysis 14 (15) , 11584–11590. 10.1021/acscatal.4c02365

Preview

PDF - Published Version Available under License Creative Commons Attribution. Download (2MB) | Preview

Abstract

The ability to introduce noncanonical amino acids as axial ligands in heme enzymes has provided a powerful experimental tool for studying the structure and reactivity of their FeIV═O (“ferryl”) intermediates. Here, we show that a similar approach can be used to perturb the conserved Fe coordination environment of 2-oxoglutarate (2OG) dependent oxygenases, a versatile class of enzymes that employ highly-reactive ferryl intermediates to mediate challenging C–H functionalizations. Replacement of one of the cis-disposed histidine ligands in the oxygenase VioC with a less electron donating Nδ-methyl-histidine (MeHis) preserves both catalytic function and reaction selectivity. Significantly, the key ferryl intermediate responsible for C–H activation can be accumulated in both the wildtype and the modified protein. In contrast to heme enzymes, where metal-oxo reactivity is extremely sensitive to the nature of the proximal ligand, the rates of C–H activation and the observed large kinetic isotope effects are only minimally affected by axial ligand replacement in VioC. This study showcases a powerful tool for modulating the coordination sphere of nonheme iron enzymes that will enhance our understanding of the factors governing their divergent activities.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Chemistry Cardiff Catalysis Institute (CCI)
Publisher:	American Chemical Society
ISSN:	2155-5435
Date of First Compliant Deposit:	2 August 2024
Date of Acceptance:	8 July 2024
Last Modified:	06 Aug 2024 11:46
URI:	https://orca.cardiff.ac.uk/id/eprint/171128

Actions (repository staff only)

Edit Item