Professor Paul Walton

01904 324457
Email: paul.walton@york.ac.uk

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 as part of the copper's coordination sphere (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 like 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 (free access until July 2, 2016), and Trends in Biotechnology, 2015

This work has recently been recognised by the RSC's 2016 Joseph Chatt award.

Figure: Copper histidine brace in an LPMO.

New (April 2016): 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 (free access until 2 July, 2016).

Biography

Paul Walton obtained his PhD degree in 1990, followed by two years as a NATO postdoctoral fellow at the University of California, Berkeley, working with Ken Raymond. He joined the department of chemistry at York in 1993 as a lecturer, becoming full professor in 1999. Between 2004 and 2010 he was chair of department. He is recipient of the Royal Society of Chemistry's Higher Education Teaching Award and the RSC's Joseph Chatt Award for outstanding multidisciplinary research.  He has also been 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. He is a strong advocate of gender equality and lectures widely on the subject.