Peptide-based chemical models for lytic polysaccharide monooxygenases

Area of Science:

• Bioinorganic Chemistry
• Biophysical Chemistry
• Enzyme Mimicry

Background:

• Lytic polysaccharide monooxygenases (LPMOs) are copper-containing enzymes crucial for biomass degradation.
• Understanding LPMO active sites requires small molecular models to study their catalytic mechanisms.
• Copper coordination chemistry of N-terminal peptides is vital for mimicking LPMO active sites.

Purpose of the Study:

• To synthesize and characterize copper(II) complexes of HPH-NH2 (L1) and HPHPY-NH2 (L2) peptides as functional models of LPMOs.
• To investigate the coordination properties and catalytic activity of these complexes in the presence of oxidants and substrates.
• To elucidate the reaction mechanisms, including the role of dimer formation and hydroperoxo intermediates.

Main Methods:

• pH-potentiometry to determine protonation constants and metal binding.
• UV-vis, Circular Dichroism (CD), and Electron Paramagnetic Resonance (EPR) spectroscopy for structural and electronic characterization.
• Enzymatic assays using H2O2 and a substrate (PNPG) to evaluate catalytic activity.

Main Results:

• Novel dimer complexes (Cu2HxL2) were formed, differing from typical ATCUN-type coordination due to proline residues.
• These dimer complexes demonstrated functional mimicry of LPMOs, catalyzing substrate oxidation with H2O2 at neutral pH.
• In the presence of H2O2, dimer complexes formed transient mononuclear hydroperoxo complexes, which decomposed to Cu(I) species, but dioxygen evolution was suppressed with PNPG.

Conclusions:

• The studied copper(II) peptide complexes, particularly dimers, are effective functional models for LPMOs.
• The coordination environment and reactivity of these models provide insights into LPMO catalytic cycles.
• The absence of dioxygen evolution in the presence of substrate suggests a productive catalytic cycle involving Cu(I)-H2O2 intermediates.