Issue 13, 2024

A frontier-orbital view of the initial steps of lytic polysaccharide monooxygenase reactions

Abstract

Lytic polysaccharide monooxygenases (LPMOs) are copper enzymes that oxidatively cleave the strong C–H bonds in recalcitrant polysaccharide substrates, thereby playing a crucial role in biomass degradation. Recently, LPMOs have also been shown to be important for several pathogens. It is well established that the Cu(II) resting state of LPMOs is inactive, and the electronic structure of the active site needs to be altered to transform the enzyme into an active form. Whether this transformation occurs due to substrate binding or due to a unique priming reduction has remained speculative. Starting from four different crystal structures of the LPMO LsAA9A with well-defined oxidation states, we use a frontier molecular orbital approach to elucidate the initial steps of the LPMO reaction. We give an explanation for the requirement of the unique priming reduction and analyse electronic structure changes upon substrate binding. We further investigate how the presence of the substrate could facilitate an electron transfer from the copper active site to an H2O2 co-substrate. Our findings could help to control experimental LPMO reactions.

Graphical abstract: A frontier-orbital view of the initial steps of lytic polysaccharide monooxygenase reactions

Supplementary files

Article information

Article type
Paper
Submitted
20 ဒီ 2023
Accepted
23 ဖေ 2024
First published
26 ဖေ 2024

Dalton Trans., 2024,53, 5796-5807

A frontier-orbital view of the initial steps of lytic polysaccharide monooxygenase reactions

E. K. Wieduwilt, L. Lo Leggio and E. D. Hedegård, Dalton Trans., 2024, 53, 5796 DOI: 10.1039/D3DT04275H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements