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Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent

Posted on August 8, 2026 at 07:25:26 AM by rkm

Nautilus Magazine

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The evolution of life is an incredibly improbable event, and as far as we know, it’s only happened once in our solar system—or so we thought. According to a new paper published in Science Advances life has actually evolved twice, right here on Earth.
Before life existed on our planet, the areas around hydrothermal vents in the ocean created the kind of primordial soup conducive to its evolution. But how did life emerge from the muck? To find out, an international team of researchers led by scientists from Heinrich-Heine University in Germany investigated the origins of the suite of chemical reactions life uses to, well, exist.
One “non-negotiable property of life,” the authors write, is our metabolism, the more than 400 complex chemical reactions organisms use to convert energy in a usable form. So to trace the origins of life, they traced the evolution of the enzymes responsible for those reactions back in time.
The genes for these enzymes are highly conserved (meaning unchanged) until you get to a certain point: the split between bacteria and archaea. While archaea are single-celled prokaryotes like bacteria, they differ enough from both bacteria and the rest of life to warrant their very own domain. They also inhabit some of the most extreme environments on Earth (including our guts).
“The surprise is that the enzymes that catalyse those reactions aren’t conserved across the evolutionary divide that separates bacteria and archaea,” study co-author William Martin of Heinrich-Heine University said in a statement. “We found that the last universal ancestor of all cells, LUCA, possessed enzymes for only about half of the reactions of metabolism.”
How then did the LUCA metabolize energy?
According to the team, the rest of its metabolic enzymes weren’t enzymes at all. Instead, LUCA used transition metals littered around hydrothermal vents to serve the same catalytic process. “The closer we look, the more clearly we can see that early biochemical evolution was a hybrid of enzymatic and metal catalysts,” explained study co-author Joseph Moran from the University of Ottawa.
That means whatever existed before LUCA relied entirely on metals to harness energy.
As they transitioned from leaning on their environments to metabolize energy to become more self-sufficient, bacteria and archaea each evolved their own new enzymes to replace the metals in these reactions. “The new data leave only one conclusion,” Martin said. “The bacteria and archaeal lineages made the transition to the free-living state independently. Only free-living cells are alive. Let’s call it by name: We are looking at one origin of the genetic code, but two origins of life.”
After all, the evolution of life may be an improbable event, but if the conditions are ripe for it to happen once, why not twice?
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Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent
Natalia Mrnjavac https://orcid.org/0009-0009-2849-6304, Nadja K. Hoffmann https://orcid.org/0009-0007-3294-5112, Manon L. Schlikker https://orcid.org/0009-0007-8175-5155, Maximilian Burmeister, [...] , and William F. Martin https://orcid.org/0000-0003-1478-6449+12 authors Authors Info & Affiliations
Science Advances
5 Aug 2026
Vol 12, Issue 32
DOI: 10.1126/sciadv.aef3128



Abstract
The origin of life required the emergence of metabolism, an autocatalytic network of enzymatic reactions that synthesize amino acids, nucleotides, and cofactors. At the origin of metabolism, there were no enzymes—how did it start? Empirical studies addressing early metabolic evolution are lacking. Harnessing protein structures for metabolic enzymes, we identify intermediate states in primordial metabolic assembly. We show that enzymatic metabolism in the universal common ancestor was incomplete, undergoing final assembly independently in the lineages leading to bacteria and archaea. Native transition metals—iron, cobalt, nickel, and palladium—served as the catalytic forerunners of both enzymes and cofactors at metabolic origin, while phosphite supplied energy, as it phosphorylates adenosine 5′-monophosphate to adenosine 5′-diphosphate and serine to phosphoserine using native metal catalysts in water. Phosphite and native metals occur in serpentinizing hydrothermal systems, identifying an energy-supplying, catalytic site of metabolic origin. Cofactors liberated nascent metabolism from native metal catalysts, engendering its autocatalytic state.

INTRODUCTION
Metabolism is a non-negotiable property of life. It transforms environmental compounds into the building blocks of life and the chemical substance of cells. Although modern metabolism is catalyzed by enzymes, at origins, there were no enzymes, leaving only the environment as the source of compounds and catalysts that spawned the first metabolic networks. However, the environment in which life and metabolism arose is hotly debated, suggestions including ultraviolet (UV)-rich terrestrial hot springs (1), terrestrial cyanide deposits (2), volcanos (3, 4), ice (5), and submarine hydrothermal vents (6–8). Because the environment of origins conditions its chemistry, almost everything about the origin of metabolism is debated, including the roles of energy (9), genetics (10), autocatalysis (11), phosphate (12, 13), cofactors (14), cyanide (15), CO2 (3), and water (16). However, on one aspect, all will agree: The ∼400-reaction network that converts H2, CO2, NH3, H2S, and phosphate into amino acids, nucleobases, and cofactors (17) cannot have arisen in an instant. Its emergence from spontaneous environmental reactions had to traverse intermediate states of assembly, which have previously been elusive.
A key question about metabolic origin concerns its state in the last universal common ancestor (LUCA) (18, 19). Was LUCA able to synthesize all of its metabolic intermediates itself or were some still supplied by the environment, and were all of LUCA’s reactions catalyzed by enzymes or did the environment supply catalysts that served as the forerunners of LUCA’s enzymes? In addition, if the environment supplied compounds and catalysts for LUCA, then how far did that dependency extend into the lineages leading to the last common ancestors of bacteria and archaea (LBCA and LACA), respectively? The processes of enzyme origins and metabolic assembly across the deepest divide of the tree of life have hitherto not been studied.
The 400 reactions of metabolism and corresponding enzymes can provide insights into the earliest phases of biological divergence, but they might also harbor evidence for the kind of environment within which metabolism arose. Do reactions and enzymes that trace to LUCA indicate a different kind of chemistry or a different environment from those that trace to LACA and LBCA, and can the different theories for the site of life’s origin be discriminated on the basis of metabolism’s chemistry? Neither question has been explored on the basis of metabolism’s conserved 400 reaction set...

https://www.science.org/doi/10.1126/sciadv.aef3128?

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