Researchers at the Center for Synthetic Microbiology (SYNMIKRO) at Philipps University Marburg and TU Berlin have made a significant breakthrough in understanding the activation of methyl-coenzyme M reductase (MCR) – the enzyme responsible for nearly all biological methane production and one of the most abundant enzymes on Earth. Their findings, published in the prestigious journal Nature, not only shed new light on one of nature’s oldest energy-generating processes but also reveal an unexpected evolutionary connection to nitrogen fixation.
In this initial step of the global nitrogen cycle, microorganisms capture nitrogen from the atmosphere and convert it into forms usable by living organisms. “Basic research in the field of biological energy and matter transformation holds great potential for addressing current challenges such as the world’s growing energy demand and advancing climate change,” explains Dr. Christian Lorent, co-author of the Nature publication and research associate at the Excellence Cluster Unifying Systems in Catalysis (UniSysCat), based at TU Berlin.
Two Sides of a Greenhouse Gas
Methanogenic archaea are microorganisms that have existed for billions of years and produce up to one billion tons of methane annually, for example in the stomachs of ruminants or in wetlands. While methane is a potent greenhouse gas contributing to global warming, biological methane production also holds great promise as a renewable energy source through biogas generation in agriculture. A deeper understanding of the fundamental mechanisms behind methane formation can drive progress in sustainable energy technologies and climate protection.
One of Nature’s Most Challenging Redox Reactions
At the heart of biological methane production lies MCR, a highly specialized enzyme whose active site contains the unique coenzyme F430. The function of this cofactor critically depends on a central nickel ion that must be in the oxidation state Ni(I) to catalyze methane production. Activating nickel to this state requires overcoming a significant energy barrier – making it one of the most demanding redox reactions in nature. How early lifeforms managed this activation had long remained a mystery.
In their study, the research team succeeded in isolating and characterizing the MCR activation complex from the model organism Methanococcus maripaludis. “We found that a small protein called McrC, together with other methanogenic marker proteins, activates the MCR through an ATP-dependent process, thereby providing the necessary energy for methane production,” explains Fidel Ramírez-Amador of Philipps University Marburg, one of the study’s lead authors.
Spectroscopic Studies Provided the Missing Proof
Remarkably, the researchers were able to show that the activation mechanism requires three uniquely structured and highly specialized metal complexes, previously known only from nitrogenase – the only enzyme capable of converting atmospheric nitrogen into biologically available forms. “Spectroscopic analyses provided the missing proof that these cofactors are composed of iron and sulfur and are likely essential for electron transfer,” says Dr. Christian Lorent. Dr. Jan Schuller of Philipps University Marburg, senior author of the study, adds: "This striking similarity suggests that these systems have a common evolutionary origin despite having completely different functions. Our study establishes an unprecedented evolutionary link between two fundamental biological processes: methanogenesis and nitrogen fixation."
"The most elegant solutions for generating energy and the most efficient catalysts have been optimized in nature over millions of years of evolution. It is our task as scientists to find, understand and apply them," summarizes Dr. Christian Lorent. In UniSysCat, he is researching the reaction mechanisms and coupling of various metalloenzymes, which can also produce hydrogen or bind the greenhouse gas carbon dioxide, for example.