Metabolism of the primordial cell reconstructed –

Where did the very first cell get the energy for its metabolism? And what were the reactions? A German-Austrian research team could now have found an answer to this question. In their analyzes of the metabolism of primitive microbes, they identified 402 metabolic reactions that the common ancestor of all life probably already had. In the presence of hydrogen and heat, as is the case with hydrothermal sources, the majority of these reactions take place without additional energy input, the team found. This suggests the possible origin of life in such deep sea hot springs.

How and where first life came about is still one of the great mysteries of biology. It seems clear that important building blocks of life such as proteins and RNA must have arisen before the first cells are formed. According to current assumptions, these molecules could have formed purely chemically in favorable environments such as rock spores, warm, mineral-rich pools or in certain hydrothermal vents on the sea floor. Enclosed in small vesicles made of lipids or other chemical compounds, the building blocks of life could have formed the first metabolic reactions in a kind of protocell. What reactions these were and where they got their energy from, however, is open.

Back to the first cell

“We wanted to know where the original metabolism got its energy from,” explains first author Jessica Wimmer from Heinrich Heine University in Düsseldorf. “Because four billion years ago there weren’t any enzymes that would catalyze the reactions in today’s cells. Rather, the reactions had to be able to take place on their own in the environment of that time. ”For their study, Wimmer and her colleagues first tried to reconstruct the original, oldest metabolic reactions using genetic and biochemical comparisons of various bacteria and archaea. They identified 402 reactions that occurred in all of the microbes examined and have probably remained almost unchanged since the beginning of life. These include the chemical reactions through which the bases of the genetic material molecules RNA and DNA are created, but also metabolic pathways for the formation and processing of the 20 essential amino acids, 18 vitamins and the synthesis of proteins.

According to the research team, the network of these 402 reactions, which is preserved in almost all of the organisms examined, suggests that it also existed in the last common ancestor of all life (Last Universal Common Ancestor, LUCA). The analyzes also showed that these reactions are based on basic raw materials such as hydrogen, carbon dioxide and ammonia – molecules that were abundant in hydrothermal vents, for example. However, this raises the question of where the necessary energy for the early metabolic reactions came from.

Metabolism of LUCA: Each circle represents one of the 402 reactions, the color indicates the energy balance: Green reactions release energy, violet ones require additional energy from the outside. (Image: HHU / Jessica Wimmer)

No additional energy required

“There have been many speculations as to where the driving energy could have come from. But nobody had looked in the metabolism itself, ”says Wimmer. But that is exactly what she and her team did. With the help of complex computer models, they examined the energy balance of each of the 402 reactions based on their free energy, also known as Gibbs energy. Whether a reaction takes place spontaneously and without absorbing additional external energy, however, depends on the environmental conditions. The research team therefore ran through the reactions at different pH values, temperatures and concentrations of the starting materials. The result: The energetically optimal conditions for the possibly first metabolic reactions were in the range of an alkaline pH value around pH 9 and at a temperature of around 80 degrees Celsius. Also, hydrogen needs to be present to help fix CO2. “Nothing works without hydrogen, because it is needed to smuggle the CO2 into the metabolism in the first place,” explains Wimmer.

If these conditions are met, however, the majority of the reactions examined take place without any additional energy input and in some cases even release energy, which then triggers the subsequent reactions. “This is exciting because the otherwise so complicated metabolism suddenly reveals a natural tendency to develop on its own under the right conditions,” says senior author William Martin from the University of Düsseldorf. The primary metabolism itself could therefore have served as an internal source of energy for the first beginnings of life. “We have shown that the energy at the origin of life is of a purely chemical nature. We don’t need any sunlight, no meteorites, no UV light: only hydrogen and carbon dioxide plus a little ammonia and salt, ”says Wimmer.

It is precisely these ingredients that could have been found by the first cells in hot, alkaline vents in the deep sea. “This milieu corresponds exactly to the environment found in the hydrothermal field ‘Lost City’ in the Atlantis massif, an undersea mountain range in the Central Atlantic,” explains Martin. The team’s results thus support the assumption that such hot springs on the ocean floor may have played an important role in the origin of life.

Source: Jessica Wimmer (Heinrich Heine University Düsseldorf) et al., Frontiers in Microbiology, doi: 10.3389 / fmicb.2021.793664

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