Professor Paul Walton of the University of York

"The active sites of copper oxygenases and their reactivity with H2O2"

Lytic polysaccharide monooxygenases (LPMOs) are relatively recently discovered enzymes that catalyse the oxidation of polysaccharides, leading to chain cleavage. LPMOs has transformed our understanding of biomass degradation, and—moreover—are now critical components in the enzymatic breakdown of biomass in the second generation bioethanol industry.1 We and others have also recently shown that LPMOs are key virulence factors in major plant diseases.2

Active site structure of an LPMO and oxidized amino acids (red) following treatment with H2O2.

We have also examined the action of oxidizing agents on the enzyme which has been shown to enhance the activity of the enzymes on saccharidic substrates, but also lead to rapid inactivation of the enzyme, presumably through protein oxidation.3 In this talk, in addition to a description of the structure and reactivity of LPMOs, I will show that the use of UV/vis, CD, XAS, EPR, MCD, MS and resonance Raman spectroscopies augmented with DFT calculations, reveals the way in which copper oxygenases deal with oxidizing species generated from uncoupled turnover of peroxide in the absence of substrate.4

[1] K. E. H. Frandsen, P. H. Walton et al, Nature Chem. Biol. 298—303 (2016).
[2] F. Sabbadin, P. H. Walton et al, Science, 373, 774-779 (2021).
[3] A. Paradisi, P. H. Walton et al, J. Am. Chem. Soc. 18585—18599 (2019).
[4] J. Zhao, P. H. Walton et al, J. Am. Chem. Soc. 20672–20682 (2023).