Professor Paul Walton

01904 324457

Research: Bioinorganic chemistry

Lytic Polysaccharide Monooxygenases (LPMOs) and the histidine brace

LPMOs have a copper-containing active site with an N-terminal (sometimes N-methylated) histidine (Proc. Nat. Acad. Sci.2011).  The active site was discovered in 2011 and is known as the histidine brace. LPMOs play a key role in the commercial production of second generation biofuels, by catalysing the oxidation of recalcitrant polysaccharides such as cellulose.  Our current research interests involve understanding the catalytic mechanisms of these enzymes using a combination of structure, spectroscopy and theory.  See reviews: Curr. Opin. Chem. Biol. 2016, and Nature Catalysis 2018.  We have also recently published an article on the experimental methods that can be used to isolate and study LPMOs.  Methods in Enzymology, 2018.  This work has been recognised by the RSC's Joseph Chatt award and the IChemE's Global Award for energy research. 

Mechanism of Cu(I)-LPMO reaction with hydrogen peroxide and O2 (open access publication)

Building on our earlier structural and spectroscopic work into LPMO-substrate interactions Nature Chemical Biology, we had previously performed small molecule DFT and large molecular QM/MM (with Professor Carme Rovira and Binju Wang) on the reaction of AA9-LPMO with hydrogen peroxide (ACS Catalysis).  Our findings revealed a potential mechanism in which Cu(II)-OH and hydroxyl radical form together within an active site 'cage' in the presence of substrate.  The cage then directs the reaction of the hydroxyl and the Cu(II)-OH to give a Cu(II)-oxyl  The Cu(II)-oxyl is then able to effect a hydrogen atom abstraction from the saccharidic substrate in a site specific manner.  These calculations have now been extended to show that the hydrogen peroxide can be generated from the addition of O2 and reducing agents to AA9-LPMO (ACS Catalysis).  The O2 and H2O2 reactive pathways can therefore be connected into a single catalytic pathway for AA9 LPMOs.  In this work we highlight the importance of substrate interaction with the LPMO in determining what oxidative mechanism the LPMO will follow.

AA9 LPMO and G3 

Figure: Structure of the active site of AA9 LPMO in contact with cellotriose, and X-band EPR spectra of same species (red) along with simulation (black).  

  • The Molecular Mechanisms of Oxygen Activation and Hydrogen Peroxide Formation in Lytic Polysaccharide Monooxygenases, B Wang, P H Walton, C Rovira ACS Catalysis, 2019, asap (open access article)
  • Bracing copper for the oxidation of C-H bonds, L Ciano, G J Davies, W B Tolman, P H Walton Nature Catalysis, 2018, 1(8), 571-577.
  • An ancient family of lytic polysaccharide monooxygenases with roles in arthropod development and biomass digestion. F Sabbadin, G R Hemsworth, L Ciano, B Henrissat, P Dupree, T Tryfona, R D S Marques, S T Sweeney, K Besser, L Elias, G Pesante, Y Li, A A Dowle, R Bates, L D Gomez, R Simister, G J Davies, P H Walton, N C Bruce, S J McQueen-Mason, Nature Commun., 2018, 9, 756.
  • QM/MM Studies into the H2ODependent Activity of Lytic Polysaccharide Monooxygenases: Evidence for the Formation of a Caged Hydroxyl Radical Intermediate. B Wang, E M Johnston, P Li, S Shaik, G J Davies, P H Walton, C Rovira, ACS Catalysis, 2018, 8, 1346-1351.
  • Lytic xylan oxidases from wood-decay fungi overcome biomass recalcitrance. M Couturier, S Ladevèze, G Sulzenbacher, L Ciano, M Fanuel, C Moreau, A Villares, B Cathala, F Chaspoul, K Frandsen, A Labourel, I Herpoël-Gimbert, S Grisel, M Haon, N Lenfant, H Rogniaux, D Ropartz, G Davies, M-N Rosso, P H Walton, B Henrissat, J-G Berrin, Nature Chem. Biol., 2018, 14(3), 306-310.
  • Structural and electronic determinants of lytic polysaccharide monooxygenase reactivity on polysaccharide substrates. T J Simmons, K E H Frandsen, L Ciano, T Tryfona, N Lenfant, J C Poulsen, L F L Wilson, T Tandrup, M Tovborg, K Schnorr, K S Johansen, B Henrissat, P H Walton, L Lo Leggio, P Dupree, Nature Commun., 2017, 8, 1064.


Paul Walton obtained his PhD in 1990 (University of Nottingham, UK), followed by two years as a NATO/SERC postdoctoral fellow at the University of California, Berkeley, USA. He joined the Department of Chemistry at York as a faculty member in 1993. Between 2004 and 2010 he was chair of department. His main research area is bioinorganic chemistry, in which he has made contributions to the understanding of copper oxidases, including the discovery of the histidine brace.  He is the recipient of multiple awards: the Royal Society of Chemistry's Higher Education Teaching Award, the RSC's 2016 Joseph Chatt Award for outstanding multidisciplinary research, the IChemE's Global Award for energy research, and the Royal Society's inaugural Athena Prize for gender equality work (runner up). He has also been the editor of Dalton Transactions (2004-2008), chair of Heads of Chemistry UK, chair of the Royal Society of Chemistry's Diversity Committee and is one the RSC's 175 Faces of Chemistry. Paul is an internationally-known advocate of equality in sciences and lectures widely on the subject.