While methane accounts for about 16% of the abundance in the atmosphere of greenhouse gases - which also include carbon dioxide, nitrous oxide, water vapor – it is more than 25 times better than carbon dioxide at trapping heat. Two-thirds of global methane release is believed to be through natural emission during anaerobic activity of primitive single-celled microorganisms called archaea. Understanding the precise mechanism by which archaea produce methane could lead to technology that reduces methane production by archaea and helps in the fight against global warming.
Archaea are distinct from bacteria mainly because of their habitat and sources of energy. The so-called methanogen archaea emit methane as a byproduct of energy generation necessary for their survival. The biomolecule responsible for methane formation is the so-called Methyl-Coenzyme M Reductase (or MCR) protein that induces the chemical conversion. In order for MCR to catalyze this reversible reaction, it needs to be activated by a partner protein that belongs to the superfamily of B12-dependent radical S-Adenosyl-L-Methionine (or SAM) enzymes.
The superfamily of radical SAM enzymes contains over 200,000 independent-sequenced proteins. It has been associated with a multitude of natural processes, including the biosynthesis of antibiotics and chlorophyll. One of these key enzymes (Mmp10) is responsible for the activation of the MCR protein and is therefore involved in the regulation of its methane formation. The ubiquity of SAM enzymes across the biosphere reflects their importance in catalyzing reactions that are fundamental to all types of life. However, the mechanisms balancing their biological activities remains poorly understood.
To decipher the activities of the Mmp10 SAM enzyme, Dr. Olivier Berteau, from the Micalis Institute, Université Paris-Saclay, assembled a team of scientific experts with various complementary areas of expertise, including other researchers from that university, Aix Marseille University and Synchrotron SOLEIL in France, as well as Nagoya University in Japan. The results of the investigation were published online in the journal Nature on Feb 2, 2022.
Key to the activity of B12-dependent radical SAM enzymes is a simple yet powerful mechanism for triggering the catalytic reaction. The difficulty in getting the enzyme to simultaneously accommodate all the actors involved in the reaction has meant that little structural information had been available that could help explain how the reaction works.
To remedy this, the research team combined crystallographic results with biochemical and biophysical data to explain how B12-dependent radical SAM proteins regulate their activity, down to atomic-level details. The Mmp10 enzymatic mechanism was imaged with all actors of the reaction present.
The results of this research have implications for the development of biotechnologies that would control key enzymatic events, particularly those implicated in methane emission, helping in the fight against global warming.
Co-author Professor Leo Chavas, of Nagoya University, is excited by the results of this long-term investigation. “A total of 137 proteins were screened at a leading synchrotron facility in France to get a glimpse of these rare events, which are so difficult to catch. This research also opens the door to biotech developments.”
The paper, "Crystallographic snapshots of a B12-dependent radical SAM methyltransferase", was published in the journal Nature, Feb 2, 2022 and is available at doi.org/10.1038/s41586-021-04355-9.
Cameron D. Fyfe, Noelia Bernardo-García, Laura Fradale, Alain Guillot, Clémence Brewee, Alhosna Benjdia, Olivier Berteau (Micalis Institute, France); Stéphane Grimaldi (Aix-Marseille University, France); Pierre Legrand (Synchrotron SOLEIL, France); Leonard Michel Gabriel Chavas (Nagoya University, Japan).
Contact: Professor Leonard Chavas
Synchrotron Radiation Research Center and Department of Applied Physics, Graduate School of Engineering, Nagoya University
Phone : +81 52-789-5286
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This work was supported by the European Research Council (ERC consolidator grant 617053), ANR (ANR-17-CE11-0014) and the CHARMMMAT Laboratory of Excellence (ANR-11-LABX0039).
About Nagoya University, Japan
Nagoya University has a history of about 150 years, with its roots in a temporary medical school and hospital established in 1871, and was formally instituted as the last Imperial University of Japan in 1939. Although modest in size compared to the largest universities in Japan, Nagoya University has been pursuing excellence since its founding. Four of the 21 Japanese Nobel Prize-winners since 2000 did all or part of their Nobel Prize-winning work at Nagoya University: two in Physics - Isamu Akasaki and Hiroshi Amano in 2014; and two in Chemistry - Ryoji Noyori in 2001 and Osamu Shimomura in 2008. Two Nobel Prize winners in Physics - Toshihide Maskawa and Makoto Kobayashi in 2008 - were graduate school alumni of Nagoya University and returned there after receiving their Nobel Prize. In mathematics, Shigefumi Mori did his Fields Medal-winning work at the University. A number of other important discoveries have also been made at the University, including the Okazaki DNA Fragments by Reiji and Tsuneko Okazaki in the 1960s; and depletion forces by Sho Asakura and Fumio Oosawa in 1954.
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Crystallographic snapshots of a B12-dependent radical SAM methyltransferase
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The authors declare no conflict of interest.