Minimalist De Novo Design of an Artificial Enzyme

We employed a reductionist approach in designing the first heterochiral tripeptide that forms a robust heterogeneous short peptide catalyst similar to the histidine brace active site of lytic polysaccharide monooxygenases. The histidine brace is a conserved divalent copper ion-binding motif that comprises two histidine side chains and an amino group to create the T-shaped 3N geometry at the reaction center. The geometry parameters, including a large twist angle (73 degrees) between the two imidazole rings of the model complex, are identical to those of native lytic polysaccharide monooxygenases (72.61 degrees). The complex was synthesized and characterized as a structural and functional mimic of the histidine brace. UV-vis, vis-circular dichroism, Raman, and electron paramagnetic resonance spectroscopic analyses suggest a distorted square-pyramidal geometry with a 3N coordination at pH 7. Solution- and solid-state NMR results further confirm the 3N coordination in the copper center of the complex. The complex is pH-dependent and could catalyze the oxidation of benzyl alcohol in water to benzaldehyde with yields up to 82% in 3 h at pH 7 and above at 40 degrees C. The catalyst achieved 100% selectivity for benzaldehyde compared to conventional copper catalysis. The design of such a minimalist building block for functional soft materials with a pH switch can be a stepping stone in addressing needs for a cleaner and sustainable future catalyst.

Automated summary

In this study, we designed the first stable heterochiral tripeptide catalyst using a reductionist approach and successfully mimicked the histidine brace active site of lytic polysaccharide monooxygenases. The pH-dependent catalyst showed high efficiency in catalyzing the oxidation of benzyl alcohol to benzaldehyde in water.