While humans burn methane to generate energy to warm their homes, some gifted microbes “burn” methane without oxygen to acquire cellular energy. This process is carried out by a specific group of microbes called ANaerobic MEthanotrophic archaea (ANMEs for short), which munch on methane to spit out CO2. Why would these invisible life forms matter ? Because they are prime actors in the planetary carbon cycle. In marine sediments without oxygen, ANMEs consume about 70% of methane before it is released into the atmosphere. In terrestrial and freshwater systems, ANMEs can consume half of the emitted methane. Therefore, due to their remarkable chemistry, they prevent the accumulation of the greenhouse gas methane in our atmosphere and play a crucial role in the carbon budget. Describing how ANMEs transform methane into CO2 is of great interest not only to environmental microbiologists but also to chemists, who can learn from the wonders of the microbial realm to produce efficient catalysts. Unfortunately, no ANMEs have been isolated so far on a Petri dish or in culture, which restricts the biochemical investigation of the enzymes performing the chemical reactions.
Researchers from the IBS, the ESRF, the Max Planck Society (Marine Microbiology, Bremen, and Terrestrial Microbiology, Marburg), and Radboud University (the Netherlands) collaborated to decipher how ANMEs capture methane. They did so in an unconventional way. If ANMEs cannot be isolated, then the enzyme of interest will be directly purified from a microbial community. In this tour de force, Wagner´s group proved that it is indeed possible to isolate the enzyme capturing methane from three different biological samples : a marine enrichment cultivated over two decades, and two bioreactors enriching ANMEs from freshwater systems.
The crystal structures of the three enzymes were obtained at atomic resolution, providing the most detailed information on this system known to date. They found that the Ni-containing catalyst and the active site are identical to those of the homologous enzyme from methanogens. In other words, ANMEs capture methane with the same enzyme that generates the biological methane. Surprisingly, the three structures present a plethora of post-translational modifications, including one that has never been observed in biology : a 3(S)-methylhistidine. The modifications might offer a slight boost to overcome the challenging methane activation, which is kinetically limited under natural conditions.
These results, published in the renowned journal Nature Communications, mark the first success of the ERC Consolidator EnLightEn, which funds Dr. Wagner’s project. This scientific adventure also demonstrates that the structural biology of enzymes from the “microbial dark matter” (non-isolated microbes) can be reached through an unbiased native approach.
Atomic resolution structures of the methane-activating enzyme in anaerobic methanotrophy reveal extensive post-translational modifications. Marie-C. Müller, Martijn Wissink, Priyadarshini Mukherjee, Nicole Von Possel, Rafael Laso-Pérez, Sylvain Engilberge, Philippe Carpentier, Jörg Kahnt, Gunter Wegener, Cornelia U. Welte, Tristan Wagner. Nature Communications 2025 ; 16(1):8229. https://www.nature.com/articles/s41467-025-63387-1
Contact : Tristan Wagner (IBS/Extremophiles and Large Molecular Assemblies Group/Microbial Metabolism team)