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A research team at the former LOEWE Center SYNMIKRO at Philipps University Marburg has investigated one of the largest enzyme complexes known in nature and deciphered its extraordinary structure. Under the supervision of Prof. Dr. Jan Schuller, doctoral researcher Sophia Paul successfully characterized the so-called heterodisulfide reductase supercomplex in detail. The study's findings are now being published in the journal "Nature".

"This enzyme complex impressively demonstrates how nature has constructed complex molecular machines to generate energy efficiently under extreme conditions. What we find particularly exciting is that we were able not only to elucidate the structure of this massive system but also to observe the flexibility with which microorganisms adapt their energy production to their environment," says Prof. Dr. Jan Schuller.

The enzyme complex under study is impressively large: it has a molecular mass of approximately eight megadaltons and a diameter of around 50 nanometers, making it one of the largest known enzyme complexes in existence. For comparison, enzymes that provide energy to cells during processes like sugar breakdown typically measure only 120 kilodaltons (roughly the difference between a fully loaded truck and a small scooter). The supercomplex comprises a total of 252 protein subunits and contains more than 600 so-called cofactors – small molecular components that are crucial for the enzyme's function.

Thanks to the complex spatial organization of its numerous components, the enzyme complex can efficiently link multiple reaction steps, enabling faster and more targeted electron transfer – a process central to energy production in certain microorganisms.

The enzyme complex originates from the microorganism Methanococcus maripaludis, a type of methanogenic archaeon – a single-celled organism capable of living without oxygen. Consequently, these organisms are found in habitats with extreme conditions, such as hot springs and deep-sea sediments, or in saline ecosystems like the salt marshes along the German North Sea coast. 

These microorganisms use hydrogen to convert carbon dioxide (CO₂) into methane (CH₄). Along with carbon dioxide, methane is one of the most important greenhouse gases and contributes to global warming. A better understanding of biological methane formation therefore helps to clarify the role of such microorganisms in global carbon cycles and in the context of climate change.

The study provides new insights into the functioning of an exceptionally large biological system and reveals how microorganisms are adapted to extreme environmental conditions through highly complex molecular machines.