Jump to main content
Jump to site search

Issue 2, 2019
Previous Article Next Article

Mechanism of hydrogen peroxide formation by lytic polysaccharide monooxygenase

Author affiliations

Abstract

Lytic polysaccharide monooxygenases (LPMOs) are copper-containing metalloenzymes that can cleave the glycosidic link in polysaccharides. This could become crucial for production of energy-efficient biofuels from recalcitrant polysaccharides. Although LPMOs are considered oxygenases, recent investigations have shown that H2O2 can also act as a co-substrate for LPMOs. Intriguingly, LPMOs generate H2O2 in the absence of a polysaccharide substrate. Here, we elucidate a new mechanism for H2O2 generation starting from an AA10-LPMO crystal structure with an oxygen species bound, using QM/MM calculations. The reduction level and protonation state of this oxygen-bound intermediate has been unclear. However, this information is crucial to the mechanism. We therefore investigate the oxygen-bound intermediate with quantum refinement (crystallographic refinement enhanced with QM calculations), against both X-ray and neutron data. Quantum refinement calculations suggest a Cu(II)–O2 system in the active site of the AA10-LPMO and a neutral protonated –NH2 state for the terminal nitrogen atom, the latter in contrast to the original interpretation. Our QM/MM calculations show that H2O2 generation is possible only from a Cu(I) center and that the most favourable reaction pathway is to involve a nearby glutamate residue, adding two electrons and two protons to the Cu(II)–O2 system, followed by dissociation of H2O2.

Graphical abstract: Mechanism of hydrogen peroxide formation by lytic polysaccharide monooxygenase

Back to tab navigation

Supplementary files

Publication details

The article was received on 07 Sep 2018, accepted on 18 Oct 2018 and first published on 19 Oct 2018


Article type: Edge Article
DOI: 10.1039/C8SC03980A
Chem. Sci., 2019,10, 576-586
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

  •   Request permissions

    Mechanism of hydrogen peroxide formation by lytic polysaccharide monooxygenase

    O. Caldararu, E. Oksanen, U. Ryde and E. D. Hedegård, Chem. Sci., 2019, 10, 576
    DOI: 10.1039/C8SC03980A

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements