Metabolism may have started in our early oceans before the origin of life

Chemical reactions crucial to the formation of metabolites in modern organisms may have started spontaneously in the Earth’s early oceans. This new finding casts doubt on the accepted sequence of events thought to have led to the origin of life.

In new research funded by the Wellcome Trust, researchers at the University of Cambridge reconstructed the chemical make-up of the Earth’s earliest oceans in the laboratory. The team found the spontaneous occurrence of reaction sequences which in modern organisms enable the formation of molecules essential for the synthesis of metabolites such as amino acids, nucleic acids and lipids. These organic molecules are critical for the cellular metabolism seen in all living organisms.

One of the metabolites that was produced, ribose 5-phosphate, is particularly noteworthy, as it is an RNA precursor. Molecules like this could in theory give rise to the RNA molecules that encode information, catalyse chemical reactions and replicate.

It was previously assumed that the complex metabolic reaction sequences, known as metabolic pathways, that occur in modern cells were only possible due to the presence of enzymes. Enzymes are highly complex molecular machines that are thought to have come into existence during the evolution of modern organisms. However, the team’s reconstruction reveals that metabolism-like reactions may have occurred naturally in our early oceans, before the first organisms evolved.

Almost 4 billion years ago, life on Earth began in iron-rich oceans that dominated the surface of the planet. This was an oxygen-free world, before photosynthesis, when iron was much more soluble and able to act as a catalyst because of its different redox state. In these seas, in which single-celled Archea would later evolve, iron, other metals and phosphate facilitated a series of reactions which resemble the core of cellular metabolism - occurring in the absence of enzymes.

The findings suggest that metabolism pre-dates the origin of life and evolved through the chemical conditions that prevailed in the world’s earliest oceans.

“Our results show that reaction sequences that resemble two essential reaction cascades of metabolism - glycolysis and the pentose-phosphate pathways - could have occurred spontaneously in the Earth’s ancient oceans,” says Dr Markus Ralser at the University of Cambridge’s Department of Biochemistry and the National Institute for Medical Research, who led the study.

“In our reconstructed version of the ancient Archean ocean, these metabolic reactions were particularly sensitive to the presence of ferrous iron, which was abundant in the early oceans and accelerated many of the chemical reactions that we observe. We were surprised by how specific these reactions were,” he added.

The conditions of the prebiotic sea were reconstructed based on the composition of various early sediments described in the scientific literature, which identifies soluble forms of iron as among the most common molecules in these early oceans.

Alexandra V Turchyn from the Department of Earth Sciences at the University of Cambridge, one of the co-authors of the study, said: “We are quite certain that the earliest oceans contained no oxygen, and so any iron present would have been soluble in these oxygen-devoid oceans. It’s therefore possible that concentrations of iron could have been quite high.”

The different metabolites were incubated at temperatures of 50-90?C, similar to what might be expected close to the hydrothermal vents of an oceanic volcano. These temperatures would not support the activity of conventional protein enzymes. The chemical products were separated and analysed by liquid chromatography tandem mass spectrometry.

Some of the observed reactions could also take place in water but were accelerated by metals that served as catalysts. “In the presence of iron and other compounds found in the oceanic sediments, 29 metabolism-like chemical reactions were observed, including those that produce some of the essential chemicals of metabolism, for example precursors to the building blocks of proteins or RNA,” says Ralser.

“These results indicate that the basic architecture of the modern metabolic network could have originated from the chemical and physical constraints that existed on the prebiotic Earth.”

How the first enzymes adopted these metal-catalysed reactions remains to be established.