An international research team has published a groundbreaking study in Science Advances offering new insights into one of science’s most fundamental questions: how the metabolism that gave rise to life on Earth originated.

Modern metabolism as we know it depends on enzymes, biological molecules that act as catalysts to speed up chemical reactions in living organisms. Crucially, this includes phosphorylation, the enzyme-driven transfer of phosphate groups that underpins cellular energy metabolism and many of the biochemical reactions required for life.

Yet this presents a fundamental challenge for researchers: if enzymes are essential for metabolism, how could metabolism have emerged before enzymes existed?

The new research, led by Prof. William Martin from the Institute of Molecular Evolution at Heinrich Heine University Düsseldorf in Germany, provides a potential answer.

In it, researchers demonstrated that metal catalysts can drive several phosphorylation reactions in water at temperatures of around 50°C, conditions consistent with hydrothermal environments.

Crucially, these reactions occurred without the involvement of enzymes, showing that metals alone can facilitate a process considered central to modern metabolism.

“The key point of this study is that it shows how metals alone can catalyse various phosphorylation reactions without any enzyme involved, and under very mild conditions,” said IMDEA Materials Principal Investigator and publication co-author Prof. Harun Tüysüz.

Prof. Tüysüz was one of four principal investigators involved in the publication, alongside lead author Prof. Martin, Prof. Mirko Basen from the University of Rostock and Prof. Joseph Moran from the University of Ottawa.

“This is the kind of reaction that today is performed by enzymes inside living organisms. Demonstrating that metal catalysts can effectively replace the function of several enzymes in this process is a game changer,” Prof. Tüysüz added. “This work is going to change textbooks in the future”.

The research builds on a growing body of evidence suggesting that hydrothermal systems may have provided favourable conditions for the emergence of life.

One of the study’s most significant findings concerns phosphite (H₂PO₃⁻; P⁺³), a phosphorus-containing compound that can be generated in hydrothermal environments.

The researchers experimentally demonstrated that, in the presence of metallic catalysts like palladium and nickel, phosphite can participate in phosphorylation reactions in water.

These reactions generate phosphorylated compounds that are energetically relevant to modern biochemistry, helping explain how some of the fundamental processes that sustain life today may have originated in purely chemical systems.

Previous studies by the researchers involved have demonstrated that simple molecules such as carbon dioxide and hydrogen can be converted into increasingly complex organic compounds under hydrothermal conditions.

The new work adds another crucial piece to the puzzle by showing that metals can also support phosphorylation, opening new perspectives about the origin of energy metabolism.

This latest study focused on metal catalysts containing palladium, which were found to be especially effective. While the precise reason for this performance requires further study, the findings suggest that naturally occurring metal catalysts could have played a role analogous to that of modern enzymes and cofactors.

By combining experimental results with an analysis of hundreds of enzymes involved in the core metabolism of bacteria and archaea, the researchers concluded that the metabolism of the Last Universal Common Ancestor (LUCA) was still incomplete and depended on geochemical catalysts available in its environment.

The results suggest that many metabolic pathways continued to evolve independently in bacterial and archaeal lineages after they diverged from their common ancestor, gradually replacing environmental catalysts with cofactors and enzymes.

Importantly, Prof. Tüysüz stressed that the study does not provide a definitive account of how life began. Rather, it offers experimental evidence supporting a plausible scenario.

“Nobody knows exactly what conditions existed four billion years ago,” he concluded. “What science can do is test plausible scenarios and uncover new possibilities. We are not claiming to have solved the mystery of how life began. Rather, our findings offer a new perspective on how energy metabolism, one of the fundamental features of life, may have first emerged.”