Artificial metalloenzymes inspired by lytic polysaccharide monooxygenases Sarah Robinson, Anca Pordea, Luisa Ciano University of Nottingham, UK Hydroxylation of activated and non-activated sp 3 C-H bonds with molecular oxygen are challenging yet very desirable reaction. Synthetic strategies using metal catalysts have been developed; however, they still have limited scope and often create overoxidized side products. Nature has provided a vast array of enzymes able to achieve selective hydroxylation reactions, with iron and copper dependent enzymes excelling at it. Amongst them are lytic polysaccharide monooxygenases (LPMOs), which can activate strong C-H bonds found in polysaccharides (bond dissociation energy ≈ 100 kcal/mol). 1 LPMOs are mono-Cu enzymes and are unique for their highly conserved active site which includes two histidine residues that coordinate the copper. 2 One of the histidines is the amino terminus of the protein, resulting in the coordination of the terminal amine to the copper. This T-shaped configuration is called the “histidine brace”. Despite the interesting chemistry exhibited by these enzymes, LPMOs are not well suited for biocatalysis, due to the position of the active site on the solvent exposed surface of the protein, rather than being in a pocket suitable for binding of small molecule. To harness LPMOs’ oxidative power and selectivity, and create a bespoke biocatalyst able to carry out the transformation, we are designing a method to insert a histidine brace-like moiety into a binding pocket, hence creating a modifiable artificial metalloenzyme. References 1. Glyn R. Hemsworth, E. M. J., Gideon J. Davies, Paul H. Walton, Lytic Polysaccharide Monooxygenases in Biomass Conversion. Trends Biotechnol. 2015, 33 (12), 747-761. 2. Ciano, L.; Davies, G. J.; Tolman, W. B.; Walton, P. H., Bracing copper for the catalytic oxidation of C–H bonds. Nat. Catal. 2018, 1 (8), 571-577.
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