The research focuses on a central question in biology: how did nonliving chemistry become the organized metabolism of the first cells? Rather than examining individual reactions, the scientists analyzed metabolism as an interconnected system. They studied approximately 420 reactions that convert simple compounds thought to have been available on the early Earth—including hydrogen, ammonia and carbon dioxide—into amino acids, RNA bases, vitamins and other molecular building blocks. These reactions form a complex network in which metabolites are shared between multiple pathways, allowing the researchers to investigate not only what reactions existed, but also how the entire system may have developed.

The team compared the enzymes used by modern bacteria and archaea with the chemical reactions those enzymes perform. Enzymes are sophisticated proteins that accelerate biochemical reactions, but the study found that the enzymes carrying out corresponding reactions in bacteria and archaea are often evolutionarily unrelated. This lack of shared ancestry is significant. It indicates that the last universal common ancestor, or LUCA—the ancestral population from which all modern cellular life descended—may not have possessed the complete enzyme-based metabolism seen today. Instead, LUCA appears to have relied on a combination of enzymes and inorganic catalysts.

According to the reconstruction, LUCA had enzymes for only about half of the reactions in the metabolic network. The remaining reactions may have been catalyzed by metals naturally present in the environments where early metabolism arose. Minerals associated with hydrothermal systems can promote chemical transformations by stabilizing reactive molecules or facilitating the transfer of electrons between compounds. In this scenario, the first metabolic networks were not purely biological. They were hybrid systems in which geological catalysts performed some of the work later taken over by genetically encoded proteins.

This proposed transition from metal catalysis to enzyme catalysis unfolded in several stages. The researchers describe an initial phase dominated by inorganic chemistry, followed by a metal-enzyme hybrid stage associated with LUCA. Later, the bacterial and archaeal lineages developed independently, each adding and refining enzymes that replaced reactions once supported by the surrounding minerals. In some cases, the two groups appear to have evolved structurally different enzymes for the same essential reaction. These examples of parallel biochemical evolution provide evidence that bacteria and archaea may have acquired the capacity for free-living existence separately rather than inheriting it from a single fully independent cellular ancestor.

The study also addresses how early metabolism could have been powered. Modern cells rely heavily on ATP, or adenosine triphosphate, to drive energetically unfavorable reactions. ATP is produced through complex enzyme-dependent systems, making it unlikely that it was readily available in the earliest hydrothermal environments. The researchers propose that phosphite, a reduced form of phosphorus that can occur in hydrothermal settings, may have provided an alternative source of chemical energy. In laboratory experiments, phosphite reacted with organic compounds in water in the presence of palladium, producing phosphorylation reactions overnight.

Phosphorylation attaches phosphate groups to organic molecules and is one of the most important forms of chemical energy transfer in biology. In contemporary cells, enzymes and ATP control this process with extraordinary precision. The experiments suggest that palladium and phosphite could have performed a simpler version of the same chemistry before ATP-based energy metabolism evolved. Palladium is a powerful catalyst, and metals with related chemical properties occur in geological environments. Although the experiments do not demonstrate that palladium powered the first cells, they show how environmental chemistry might have supplied both catalysts and energy-transfer reactions before sophisticated molecular biology existed.

To determine whether the metabolic network could be arranged into a plausible sequence, researchers used mathematical methods developed for complex networks. The 420 reactions are highly interconnected, and many compounds participate in several pathways, making a simple chronological reconstruction difficult. Network specialists from the University of Canterbury and the University of Tübingen developed an approach for ordering reactions from relatively simple to more complex. The method first tests whether the network permits a unique ordering and then uses that structure to identify a possible progression for the emergence of metabolism.

The findings reshape the question of life’s origin by separating two events that are often treated as one. The genetic code may have had a single origin, and all modern cellular organisms may ultimately share ancestry through LUCA. But the emergence of free-living cells—organisms capable of maintaining metabolism outside a mineral-rich vent environment—could have occurred independently in the bacterial and archaeal lineages. The researchers therefore describe a model involving one origin of the genetic code but two origins of life in the ecological and cellular sense. The conclusion remains a scientific hypothesis, but it is supported by comparisons of genomes, protein structures, chemical reactions and laboratory catalysis.

Together, the results present early evolution as a gradual handoff between geology and biology rather than a sudden appearance of fully formed cellular machinery. Metals may have initiated and sustained key reactions, while natural selection later favored organisms that encoded more reliable catalysts in proteins. As bacterial and archaeal ancestors became increasingly independent from their mineral surroundings, they followed separate biochemical paths. The study offers a detailed framework for understanding how chemistry at ancient hydrothermal vents could have developed into the first durable forms of cellular life.

Subject of Research: Origins of life, early metabolism, hydrothermal vent chemistry, and the evolution of bacterial and archaeal cells

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

Web References: https://doi.org/10.1126/sciadv.aef3128

References: Natalia Mrnjavac, Nadja K. Hoffmann, Manon L. Schlikker, Maximilian Burmeister, Loraine Schwander, Carolina García García, Max Brabender, Mike Steel, Daniel H. Huson, Sabine Metzger, Quentin Dherbassy, Bernhard Schink, Mirko Basen, Joseph Moran, Harun Tüysüz, Martina Preiner and William F. Martin. “Intermediate stages in the origin of metabolism at a phosphorylating hydrothermal vent.” Science Advances 12, eaef3128 (2026).

Image Credits: HHU/Nadja Hoffmann

Keywords: Origins of life, metabolism, hydrothermal vents, LUCA, bacteria, archaea, enzyme evolution, metal catalysis, palladium, phosphite, phosphorylation, astrobiology

For decades, scientists have speculated that the earliest life forms utilized geochemical reactions as their primary source of energy, thriving in environments rich in hydrogen and other inorganic compounds. The latest study, led by Professor William Orsi from LMU’s Department of Earth and Environmental Sciences, offers compelling experimental validation of this idea. The team created laboratory analogues of early Earth hydrothermal vent systems, commonly referred to as “black smokers,” which are characterized by their distinctive iron- and sulfur-laden plumes on the ocean floor, and are considered to mirror the environmental conditions from 4 to 3.6 billion years ago. Notably, these ancient oceans contained high concentrations of dissolved iron, differentiating them from modern-day analogues.

In their laboratory setup, the LMU scientists engineered “chemical garden” structures—miniature replicas of seafloor hydrothermal vents—where iron and sulfur ions react at elevated temperatures to form iron sulfide minerals such as mackinawite (FeS) and greigite (Fe₃S₄). These abiotic mineral precipitations inherently generate hydrogen gas (H₂) as a byproduct, establishing a natural energy source that early life could exploit. What the researchers discovered was remarkable: the hyperthermophilic archaeon Methanocaldococcus jannaschii, isolated from modern hydrothermal sediments, was not only able to survive in these conditions but exhibited robust exponential growth without any external nutrient supplementation.

Methanocaldococcus jannaschii is a single-celled microorganism that thrives in extreme environments, and it serves as an excellent modern model for ancient methanogenic metabolic pathways, specifically those centered on acetyl-CoA chemistry. During the experiments, these archaeans elevated the expression of genes involved in the acetyl-CoA pathway in response to the chemically generated hydrogen gas. This bioenergetic adaptation demonstrates a direct link between geochemical energy fluxes and primordial biological metabolism, reinforcing theories that such chemical reactions could have sustained life before photosynthesis or oxygen-based respiration evolved.

The close physical association between the archaeal cells and the iron sulfide mineral particles observed in these experiments further parallels fossil evidence from ancient geological deposits. Such deposits frequently contain mackinawite and related mineralogical structures that preserve microbial biosignatures, suggesting that early life forms may have been intimately connected with mineral surfaces facilitating energy transfer and metabolic activity. This intimate relationship might have been essential to the survival and proliferation of early microbial communities in the harsh conditions of the Hadean and Archean oceans.

What sets this study apart is the demonstration that no additional nutrients, vitamins, or trace metals were incorporated into the experimental system, underscoring that energy derived purely from abiotic iron-sulfur precipitation reactions might have been sufficient to fuel early life’s metabolic demands. This insight erects a fundamental pillar for understanding how life could emerge and sustain itself independently of complex organic substrates, a question that has long perplexed origins-of-life research.

Moreover, the implications of this work extend beyond the confines of Earth. The researchers are exploring whether similar geochemical and microbial processes could exist elsewhere in the cosmos, specifically in extraterrestrial environments hypothesized to harbor hydrothermal-like systems. Enceladus, one of Saturn’s icy moons, is a prime candidate due to its subsurface ocean in contact with a rocky core, producing conditions analogous to the early Earth hydrothermal vents. NASA’s interest in Enceladus stems from its potential habitability, and the LMU team’s future experiments aim to simulate this environment in vitro to test the survivability and growth potential of methanogenic archaeans under such conditions.

This interdisciplinary study intertwining geology, microbiology, and planetary science not only advances our understanding of the earliest metabolic processes but also guides the search for life beyond Earth. It confirms that hydrogen-dependent methanogenesis, powered by geochemical hydrogen generated abiotically via iron-sulfur mineral precipitations, stands as the most ancient and enduring metabolic pathway identified to date. This pathway likely laid the foundation for the evolution of life, bridging inorganic geochemistry with complex biochemistry.

The findings of the LMU team prompt a reevaluation of the conditions required for life to originate and persist. It underscores the ability of simple elemental cycles—iron, sulfur, hydrogen—to drive complex biological functions in nutrient-poor environments, hinting at a universal biogeochemical principle. The archaea’s unexpected vigorous growth under such minimalist conditions highlights life’s remarkable adaptability, offering a vital clue to the energy economies of the biosphere’s most archaic roots.

Furthermore, by confirming the functionality of primordial metabolism under simulated early Earth conditions, the research completes a critical experimental circle: from fossil evidence and genetic reconstructions down to tangible biochemical demonstrations. Such comprehensive understanding is pivotal for evolutionary biology, geobiology, and astrobiology, enhancing our grasp of life’s resilience and potential universality.

The partnership with the Archaea Center at the University of Regensburg was also instrumental, providing state-of-the-art cultivation facilities essential for maintaining and experimenting with these extremophile organisms. This collaboration underscores the vital role of advanced microbiological techniques in verifying hypotheses about the origins and evolution of life.

As the LMU researchers venture into simulating extraterrestrial environments like those on Enceladus, their results could reshape our definitions of habitable zones in the solar system. If hydrogen-dependent methanogens can grow under such conditions, the possibility of life—albeit microbial and extremophilic—existing elsewhere becomes markedly more plausible. This challenges the anthropocentric and Earth-centric models that have dominated astrobiology thus far.

In a broader scientific context, this investigation exemplifies how interdisciplinary approaches, blending experimental geochemistry with molecular biology, can propel forward the frontiers of knowledge about life’s beginnings. The study published in Nature Ecology & Evolution not only establishes a new benchmark for laboratory simulation of prebiotic metabolisms but also reinvigorates the quest to uncover life’s universal biochemical origins.

As humanity inches closer to exploring worlds beyond our own, understanding the metabolic blueprints that allowed life to persist in harsh ancient environments on Earth is invaluable. The LMU team’s elegant laboratory reconstructions of early Earth conditions revive and confirm the ancient hydrogen-driven methanogenic metabolism as a cornerstone of life’s evolutionary narrative—a story that is still unfolding, both here on Earth and possibly across the cosmos.

Subject of Research: Hydrogen-dependent primordial metabolism mimicking early Earth geochemical conditions

Article Title: Simulated early Earth geochemistry fuels a hydrogen-dependent primordial metabolism

News Publication Date: 30-Apr-2025

Web References:
10.1038/s41559-025-02676-w

Keywords:
Early Earth metabolism, hydrogen-dependent methanogenesis, primordial metabolism, hydrothermal vents, iron sulfide minerals, mackinawite, greigite, Methanocaldococcus jannaschii, acetyl-CoA pathway, abiotic hydrogen production, extremophiles, astrobiology, Enceladus simulation