Decoding one of nature's largest enzymes reveals how methane is biologically produced

A research team at Marburg University has made significant strides in understanding one of the largest enzyme complexes known, revealing insights into biological methane production. On July 8, 2026, the findings were published in the journal Nature, showcasing the complex's structure and functionality in extreme environments.

Insights into the Enzyme Complex Structure

The enzyme complex, known as the Hdr–Vhu–Fwd super-assembly, has an impressive molecular mass of approximately 8 megadaltons and a diameter of about 50 nanometers. It comprises 252 protein subunits and over 600 cofactors, which are essential for its function. According to Dr. Jan Schuller, the team leader, this complex demonstrates how nature constructs intricate molecular machines that efficiently generate energy.

Many enzymes, such as those responsible for cellular energy from sugar metabolism, are typically smaller, around 120 kilodaltons. This significant size difference highlights the unique role of the Hdr–Vhu–Fwd complex in energy production within microorganisms.

Role in Methane Production

The enzyme complex is isolated from the microorganism Methanococcus maripaludis, a methanogenic archaeon that thrives in oxygen-free, extreme environments. These microorganisms convert carbon dioxide (CO₂) into methane (CH₄), which is a major greenhouse gas contributing to global warming. Understanding this biological methane production is crucial in assessing the role of these organisms in global carbon cycles and climate change.

• Key facts about the Hdr–Vhu–Fwd complex:
• Molecular mass: 8 megadaltons
• Diameter: 50 nanometers
• Number of protein subunits: 252
• Number of cofactors: 600+

Adaptability of Anaerobic Microorganisms

Using cryo-electron microscopy, the Marburg team not only visualized the complex structure but also discovered an unexpected feature: in approximately 18% of the particles examined, a formate dehydrogenase was found in place of a hydrogen-utilizing hydrogenase. This finding illustrates the adaptability of anaerobic microorganisms, allowing them to replace components of the complex when environmental conditions, like hydrogen availability, change.

The research group also employed cryo-electron tomography to study the enzymes in their natural cellular environments. The results indicated that these super-assemblies occur at high densities within cells, playing a central role in electron flow and energy production.

This study offers new insights into the functioning of an exceptionally large biological system and how microorganisms adapt to extreme living conditions through complex molecular machinery.