One of nature’s most powerful enzymes, LPMO, has a unique ability to break down tough materials. But this strength comes with a cost: the enzyme itself is vulnerable to damage. New research from NMBU now shows that evolution has worked to make the enzyme more robust.
Enzymes are proteins that initiate and accelerate chemical processes, usually without being consumed or damaged in the process.
But there is one enzyme so powerful in affecting chemical reactions that it becomes vulnerable to damage itself. It can break down materials that are normally difficult for enzymes to handle, such as cellulose in wood and chitin, a substance found in insect shells and the exoskeletons of marine animals.
The enzyme was discovered in 2010 by researchers at NMBU and was named lytic polysaccharide monooxygenase (LPMO). It turned out to be one of the world’s most powerful enzymes and is now used across the globe for various industrial applications.
LPMOs have been described as both “super-enzymes” and “nature’s nuclear warheads”. They fire oxygen into the surface of tough materials, partially degrading them so that other enzymes can break them down more easily. This makes LPMOs highly attractive for industrial processing, including biorefineries.
Researchers at NMBU have now uncovered new aspects of how nature has adapted these super-enzymes over millions of years. The findings are published in the prestigious journal PNAS (Proceedings of the National Academy of Sciences of the USA).
Can be damaged by their own strength
Powerful chemistry comes with a downside: LPMOs can be damaged by their own reactivity.
“These enzymes employ extremely powerful chemical processes. It’s completely harmless to us humans, but the enzyme itself can be damaged. When that happens, we lose active enzyme, and industrial processes become more expensive and less efficient,” says Professor Vincent Eijsink at NMBU.
In the new study, the researchers reconstructed the evolutionary development of LPMOs. They used a method called ancestral sequence reconstruction (ASR), which makes it possible to calculate and recreate ancient versions of the enzymes in the laboratory.
“By recreating the enzymes’ ancestors, we can study what LPMOs looked like in the past and how they gradually became more robust over time,” says first author Tom Emrich-Mills, postdoctoral researcher at NMBU.
The results show that the most important evolutionary pressure over millions of years has been to make the enzymes able to withstand their own powerful oxidative chemistry. The changes that strengthened the enzymes involve large portions of their protein structure.
“It’s fascinating to see how extensive the adaptations are. Evolution has refined many parts of the enzyme, spending millions of years making it better equipped to handle its own strength,” says Emrich-Mills.
New knowledge enables better industrial enzymes
For the researchers, the findings are important not only for basic science, but also for the potential to develop improved variants of LPMOs for industrial use.
“The most central outcome of this work is that we now understand which properties make LPMOs robust. This knowledge can be used to design more durable enzymes for industry and to develop synthetic catalysts inspired by nature,” says Eijsink.
The study is a milestone for NMBU’s CUBE project, an EU-funded ERC Synergy Project aimed precisely at understanding and improving nature’s most powerful catalysts.
“We are very pleased. This work comes just one month after we published another major discovery about LPMO robustness in another prestigious journal, the Journal of the American Chemical Society. It shows how rapidly knowledge is advancing now,” says Eijsink.
He emphasizes that the first author of the earlier study is Zarah Forsberg, who has been central to several major LPMO studies and is a former recipient of NMBU’s Research Award.
Fact box
- Lytic polysaccharide monooxygenases (LPMOs) are a type of enzyme discovered by NMBU researchers in 2010.
- LPMOs are extremely powerful enzymes capable of breaking down materials such as cellulose and chitin.
- The enzymes are now used in industry and processing globally.
- Researchers from NMBU’s Protein Engineering and Proteomics Group (PEP) have recently published two major papers on new discoveries related to LPMO function.
- The research is part of CUBE, an EU-funded research project at NMBU (ERC Synergy Grant). The project leader for the NMBU part of CUBE is Professor Vincent Eijsink.
Sources:
- I. Ayuso-Fernández, T.Z. Emrich-Mills, O. Golten, Z. Forsberg, K.R. Hall, L.G. Nagy, M. Sørlie, Å. Kjendseth Røhr, & V.G.H. Eijsink (2026). Redox robustness drives LPMO evolution. PNAS, 123 (3) e2521617123. https://doi.org/10.1073/pnas.2521617123
- Zarah Forsberg, Anton A. Stepnov, Ole Golten, Esteban Lopez-Tavera, Åsmund K. Røhr, Iván Ayuso-Fernández, and Vincent G. H. Eijsink (2025). Discovery of a Copper-Binding Carbohydrate-Binding Module Regulating the Activity of Lytic Polysaccharide Monooxygenases. Journal of the American Chemical Society, 147 (49), 45104–45118. https://pubs.acs.org/doi/10.1021/jacs.5c14016