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 N-methylated histidine (Proc. Nat. Acad. Sci.2011).  This active site was discovered by us 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. Struct. Biol. 2013, Curr. Opin. Chem. Biol. 2016, and Trends in Biotechnology, 2015.  This work has recently been recognised by the RSC's 2016 Joseph Chatt award and the IChemE's Global Award for energy research (with Professors Gideon Davies and Bernie Henrissat). 

Figure: Copper histidine brace in an LPMO.

Structure and spectroscopy of an LPMO-substrate complex

A combined structural, EPR spectroscopy and kinetics study reveals the molecular basis by which LPMOs could oxidatively cleave a saccharidic substrate.  Of particular note is the role of the amino terminus of the histidine brace, which is part of a hydrogen-bond network with a water molecule and the substrate.  This work is published in Nature Chemical BiologyCover article feature.

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). 

New catalytic diversity in the galactose oxidase family

Working with Harry Brumer from University of British Columbia, we have recently characterised a new class of galactose oxidases which catalyse the oxidation of unactivated alcohols, such as ethanol and propanol.  These enzymes now greatly expand the range of substrates upon which galactose oxidases are known to act and give insight into the potential mechanisms by which catalysis occurs, Nature Commun., 2015, 6, ncomms10197.

AA5 structure

Figure: Ribbon-view structure of AA5 'galactose oxidase' enzyme (copper active site shown as silver sphere).‌

Recent publications

  • The molecular basis of polysaccharide cleavage by lytic polysaccharide monooxygenases
    K E H Frandsen, T J Simmons, P Dupree, J-C N Poulsen, G R Hemsworth, L Ciano, E M Johnston, M Tovborg, K S Johansen, P von Freiesleben, L Marmuse, S Fort, S Cottaz, H Driguez, B Henrissat, N Lenfant, F Tuna, A Baldansuren, G J Davies, L Lo Leggio, P H Walton, Nature Chem. Biol., 2016, 12, 298-303.
  • Structure-function characterization reveals new catalytic activity diversity in the galactose oxidase and glyoxal oxidase family
    D Lin, S Urresti, M Lafond, F Derikvand, E M Johnston, L Ciano, J-G Berrin, B Henrissat, P H Walton, G J Davies, H Brumer, Nature Commun., 2015, 6, doi:10.1038/ncomms10197.
  • Structure and boosting effect of a starch-active lytic polysaccharide monooxygenase
    L Lo Leggio, K S Johansen, T J Simmons, J-C N Poulsen, K E H Frandsen, G R Hemsworth, M A Stringer, P von Freiesleben, M Tovborg, K S Johansen, L De Maria, P V Harris, C-L Soong, P Dupree, T Tryfona, N Lenfant, B Henrissat, G J Davies, P H Walton, Nature Commun., 2015, 6, doi:10.1038/ncomms6961.  
  • Discovery and characterization of a new family of lytic polysaccharide monooxygenases.  
    G Hemsworth, B Henrissat, G J Davies, P H Walton, Nature Chem. Biol., 2014, 10, 122-126
  • Spectroscopic and computational insight into the activation of O2 by the mononuclear Cu center in polysaccharide monooxygenases.
    C H Kjaergaard, M F Qayyum, S D Wong, F Xu, G R Hemsworth, D J Walton, N A Young, G J Davies, P H Walton, K S Johansen, K O Hodgson, B Hedman, E I Solomon, Proc. Nat. Acad. Sci., 2014, 111(24), 8797-8802.
  • Lytic polysaccharide monooxygenases in biomass conversion
    G R Hemsworth, E M Johnston, G J Davies, P H Walton, Trends in Biotechnology, 2015, 747-761.
  • On the catalytic mechanisms of lytic polysaccharide monooxygenases
    P H Walton, G J Davies, Curr. Opin. Chem. Biol., 2016, 195-207.


Paul Walton obtained his PhD in 1990, followed by two years as a NATO 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. He is the recipient of multiple awards which extend across the full range of his work, including: the Royal Society of Chemistry's Higher Education Teaching Award, the RSC's 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 gender equality and lectures widely on the subject.  He recently served on the Irish HEA's Expert Group on gender equality, the recommendations of which can be seen in the report, HEA Review of Gender Equality in Irish Higher Education Institutions.