17.04.2025 Milestone in methane research: scientists describe key enzyme in biological methane production
Piece of the climate research puzzle – basic research under the cryo-electron microscope involving members of GRK 2937 MiNu published in "Nature"
A research team at Philipps University of Marburg – involving two members of GRK 2937 MiNu – has achieved a breakthrough in methane research. In the research journal Nature, they publish new findings on the activation of methyl coenzyme M reductase (MCR), one of the most common enzymes on Earth, which is responsible for almost all biological methane production. Methane (CH4) has a significantly higher global warming potential than CO2 and contributes significantly to global climate change. The researchers led by Fidel Ramírez-Amador, Sophia Paul and Dr. Anuj Kumar from Dr. Jan Schuller's research group have isolated and characterised the MCR activation complex from a methanogenic model organism for the first time. "We found that a small protein called McrC interacts with methanogenic marker proteins (MMPs) and an ATPase in an ATP-dependent process to activate MCR," explains Ramírez-Amador, one of the study's lead authors. "Our results highlight how ATP provides the energy needed to drive this challenging activation process and enable MCR to produce methane."
Although MCR has been studied for years, the exact mechanism of its activation in methanogenic organisms has remained unclear. This is partly due to the central nickel atom of the unique cofactor F430 at the centre of the enzyme. Activating the nickel requires overcoming a considerable energy barrier, making it one of the most challenging redox reactions in nature. How early life forms achieved this activation remains an open question. "We believe that the binding and hydrolysis of ATP triggers the catalytic activation of the coenzyme F430 in MCR," reports Sophia Paul, also a first author of the study and doctoral researcher with the DFG-funded Research Training Group Nucleotide Metabolism in Microbes (MiNu, GRK 2937).
In addition, the researchers were able to identify three uniquely coordinated and highly specialised metal compounds, known as L-clusters, using cryo-electron microscopy. These were previously thought to occur only in nitrogenases, the only enzymes capable of converting atmospheric nitrogen into bioavailable forms. "With our high-resolution cryo-EM structures, we can not only reveal the details of the L-cluster at the atomic level, but also capture different functional states of the enzyme that link the activation process to the complex catalytic mechanism of MCR," explains structural biologist Dr Anuj Kumar, postdoctoral researcher and also first author of the study. "These results not only strengthen the hypothesis that methane production and nitrogen fixation have a common evolutionary origin, but also have far-reaching implications for our understanding of how complex chemical reactions proceed in low-energy environments."
"Our findings provide valuable insights for climate research, as they could help us regulate or even limit methane emissions in the long term. At the same time, they expand our understanding of the evolutionary links between two of the Earth's most important biogeochemical cycles," emphasises Dr. Jan Schuller, who is a PI of GRK 2937 MiNu. "Using state-of-the-art cryo-electron microscopy methods, we were able to create a detailed picture of this fundamental biological process for the first time."
"These research results represent a milestone in the understanding of fundamental biochemical processes and once again underline the excellence of the University of Marburg in the profile area of 'Microbiology, Biodiversity and Climate'. I am delighted for our DFG Emmy Noether Group Leader and ERC Starting Grant recipient, Jan Schuller," says Prof. Dr. Gert Bange, mentor and Vice President for Research at Philipps University of Marburg who is also a PI of GRK 2937.
Perspectives for climate research
These new findings have far-reaching implications. In climate research, understanding biological methane production could help regulate or even limit methane emissions. At the same time, they offer starting points for specifically investigating methane-degrading microorganisms that use related enzymes and potentially harnessing them for climate protection measures. In evolutionary biology, the detection of L-clusters in the activation machinery of MCR is an important step towards a better understanding of the links between methane formation and nitrogen fixation. "This could provide new insights into the development of fundamental metabolic processes and permanently change our view of the early evolution of life on Earth," reports first author Sophia Paul.
Original publication: Ramírez-Amador, F., Paul, S., Kumar, A. et al. Structure of the ATP-driven methyl-coenzyme M reductase activation complex. Nature (2025) DOI: https://doi.org/10.1038/s41586-025-08890-7
This article is a translation of the University of Marburg's German news item, including additional information on affiliations with GRK 2937 MiNu.