Originally posted 2025 June 18

Hydrogen-producing enzymes are large and extremely sensitive to oxygen. This makes their use in the production of “green hydrogen” complicated. Researchers at Ruhr-Universität Bochum and the University of Potsdam have circumvented this problem: They have transferred the catalytic center of such an enzyme - the [FeFe]-hydrogenase - which is made up of iron atoms, into a ferredoxin. These small biomolecules acts as an electron carriers in all living organisms. The artificial biohybrid can efficiently produce hydrogen gas using electrons from light-driven biological systems. The researchers have published their results in the journal Advanced Science.

Hydrogen is considered to be the clean energy carrier of the future, but its sustainable production is still a major challenge. Natural enzymes, known as hydrogenases, are highly efficient hydrogen-generating biocatalysts, but their industrial use is not yet established. With 600 amino acids, they are very large and complex and usually extremely sensitive to oxygen. In addition, they require high-energy electrons, which should also be provided in an environmentally friendly way.

[FeFe]-hydrogenases use an iron-containing molecule to produce hydrogen. This so-called cofactor functions similarly to a platinum catalyst and can be chemically synthesized. However, it is inactive as an isolated molecule and requires the protein environment to achieve its maximum performance. The researchers at Ruhr-Universität Bochum wanted to simplify the highly complex hydrogenase biocatalyst to enable its integration into industrial processes. In some microalgae, hydrogenases are supplied with electrons through photosynthesis. The electron mediator is the small iron-containing protein ferredoxin, which receives the electrons directly from the light-driven photosynthetic electron transport chain.

“We asked ourselves the biologically crazy question of whether the whole thing could be shortened and the ferredoxin could form hydrogen,” explains Vera Engelbrecht, one of the two first authors of the study. And to their own great surprise, the researchers were able to identify ferredoxins that could form hydrogen in combination with the hydrogenase cofactor. “However, we had to outsmart the biological synthesis pathways,” explains Yiting She, the other first author (pictured left). "Only very specific ferredoxins were able to work together with the cofactor. Finding this out was a long but also very exciting journey."

The high activity of the biohybrid surprised the researchers . “We know that the cooperation between protein and cofactor in natural [FeFe]-hydrogenases is very important,” explains Prof. Dr. Thomas Happe, under whose leadership the project was carried out. In collaboration with Sven T. Stripp from the University of Potsdam, the new ferredoxin hydrogenase was therefore characterized spectroscopically. “It appears that the ferredoxin protein provides a chemically favorable environment for the hydrogenase catalyst,” concludes Happe. To achieve this, the ferredoxin's own natural cofactor must be replaced by the hydrogenase cofactor using complex synthesis pathways. “Despite this, the new protein can still receive electrons from photosynthesis components,” says Yiting She. This is an important feasibility study for a small artificial metalloenzyme that mimics natural light-driven hydrogenases, but with fewer components and smaller scaffolds.

Hydrogen-Producing Catalysts Based on Ferredoxin Scaffolds. Advanced Science (2025).
Link to the publication: https://doi.org/10.1002/advs.202501897

Originally posted 2025 April 17

Researchers at the Center for Synthetic Microbiology (SYNMIKRO) of Philipps-University Marburg and University of Potsdam have made a major breakthrough in understanding the activation of Methyl-coenzyme M reductase (MCR). The MCR enzyme is responsible for nearly all biological methane production and one of the most abundant enzymes on Earth. The new findings can help to understand one of nature’s oldest energy-harvesting processes and reveal an unexpected evolutionary connection between two fundamental biological processes: methane production and nitrogen fixation.

While methane is a potent greenhouse gas that contributes to climate change, the biological transformation of carbon dioxide into methane also holds great promise as a renewable energy source. Understanding the fundamental mechanisms behind methane formation could lead to advancements in sustainable energy technologies and environmental conservation.

At the heart of biological methane production – the methanogenesis – sits the enzyme MCR with its unique nickel complex F430. In order to catalyze methane production, F430 must be reduced, which is one of the most challenging redox reactions in nature. It has long remained an open question how early life forms could conduct strongly reducing electrons into the enzyme.

In their study, the research team succeeded in isolating and characterizing the MCR activation complex from the model archaeon Methanococcus maripaludis. Methanogenic archaea are microorganisms that have existed for billions of years, producing up to one billion tons of methane annually. The new electron microscopy structure now suggests that the MCR activation complex contains three uniquely coordinated and highly specialized redox cofactors that were previously thought to be exclusive to nitrogenase – an enzyme complex that is responsible for nitrogen fixation in living organisms. “The spectroscopy yielded the final piece of evidence that the cofactors are comprised of iron and sulfur”, explains Sven T. Stripp, co-author from University of Potsdam. Jan Schuller, the study’s senior author, adds: “This striking similarity suggests that, despite performing entirely different functions, these systems share an evolutionary relationship.” He concludes: “Ultimately, our study establishes an unprecedented evolutionary connection between two fundamental biological processes: methanogenesis and nitrogen fixation.”

Methanogenesis is a process that dates back to the earliest history of life on Earth, evolutionary even predating photosynthesis. It is not only responsible for methane emissions but also forms the foundation for other metabolic networks crucial for life. A deeper understanding of these mechanisms advances both our fundamental knowledge of molecular evolution and its possible biotechnological applications, ultimately aiming to mitigate methane emissions.­

Structure of the ATP driven Methyl-coenzyme M reductase activation complex. Nature (2025).
Link zur Publikation: https://www.nature.com/articles/s41586-025-08890-7

Originally posted 2025 January 13

Sven Stripp is a physical chemist and investigates the reaction mechanism of enzymes that convert gases such as hydrogen, nitrogen or carbon dioxide. Since December 2024, he has been setting up a new working group on “Infrared difference spectroscopy of gas-processing metal enzymes” at the University of Potsdam. The junior research group, which is funded by the Heisenberg Program of the German Research Foundation (DFG), is based at the Institute of Chemistry.

“My research aims to finally clarify the reaction mechanism of the so-called [FeFe]-hydrogenase,” says Sven Stripp. Hydrogenases are enzymes that produce, bind, and convert hydrogen. [FeFe] hydrogenases are among the metalloenzymes that play a key role in microbial energy metabolism in numerous organisms. “We use infrared spectroscopy and electrochemistry to observe the metalloenzymes at work,” he explains. The aim is to gain a better understanding of the enzymes and produce similarly active, synthetic catalysts.

“Our findings can be used, for example, to produce green hydrogen or to bind nitrogen from the air in order to make barren soils fertile,” says Stripp. He is also working on enzymes that make it possible to cleanse the atmosphere of excess carbon dioxide from the combustion of fossil fuels. “As I grew up in the Ruhr area, the latter is a particular concern of mine,” jokes Stripp. In addition to the University of Potsdam, there are close collaborations with the universities in Berlin, Bochum, and Marburg.

Sven Stripp received his doctorate in plant biochemistry (Thomas Happe) from Ruhr University Bochum in 2010 and then worked as a postdoc (Joachim Heberle) and research group leader at Freie Universität Berlin, where he habilitated in physical chemistry. Until 2024, he was visiting professor of biophysical chemistry at the Technical University Berlin.