New research sheds light on origin of metabolism

The chemical reactions behind metabolism – the processes that occur within all living organisms in order to sustain life – may have begun spontaneously in the early oceans, according to new research led by Dr Markus Ralser of St John’s College.

This new finding suggests a sequence for the events thought to have led to the origin of life on Earth.

In a study funded by the Wellcome Trust and the European Research Council, a team of researchers from the University of Cambridge reconstructed the chemical make-up of Earth’s earliest oceans in the laboratory. In their experiments, the team found reaction sequences similar to those that in modern organisms enable the synthesis of sugar phosphate metabolites. These molecules represent the precursors of organic molecules such as amino acids, nucleic acids and lipids, and are essential for cellular metabolism, the process all living organisms use to survive.

In organisms, these metabolites are generated and inter-converted in complex reaction sequences known as metabolic pathways. They are made possible due to the presence of enzymes, highly complex molecular structures thought to have emerged during the evolution of living organisms. The team’s reconstruction of the ancient Archean ocean environment provides evidence that two of the most central of these metabolic pathways, known as glycolysis and the pentose phosphate pathway, might have originated based on chemical conditions present in the earliest seas. Metabolism-like reactions may have arisen naturally even before the first organisms evolved.

The discovery of one of the metabolites, ribose-5 phosphate, is particularly noteworthy. Molecules such as this could, in theory, give rise to RNA, which encodes information and replicates itself.

Dr Ralser, College Research Associate and Wellcome-Beit Prize Fellow, said: “Our results show that reaction sequences that resemble two essential reaction cascades of metabolism could have occurred spontaneously in the Earth’s ancient oceans.”

Life on Earth began almost four billion years ago, in iron-rich oceans that covered most of the planet’s surface. This was an oxygen-free world, pre-dating photosynthesis, when iron was much more soluble and able to act as a catalyst. In this environment iron, other metals and phosphate facilitated a series of reactions which resembled the core of cellular metabolism in the absence of enzymes.

“In our reconstructed version of the 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 we observe. We were surprised by how specific these reactions were” said Dr Ralser.

The conditions of the primoridal ocean were reconstructed based on the composition of various early sediments known by the scientific community. Soluble forms of iron were identified as being amongst the most common molecules in these early seas.

Alexandra Turchyn from the Department of Earth Sciences, a co-author 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 conditions. It’s therefore possible that concentrations of iron could have been quite high.”

The different metabolites used in modern cellular metabolism were incubated at temperatures of 50-90 °C, similar to what might be expected near the hydrothermal vents of an undersea volcano. These temperatures would not allow for the activity of typical enzymes. The chemical products created were then separated and analysed by liquid chromatography and tandem mass spectrometry.

Some of the observed reactions were spontaneous and accelerated by the presence of metals that served as catalysts. Dr Ralser said: “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 elements of metabolism, for example precursors to the building blocks of proteins or RNA.”

“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.”

For more information on this story, please contact Ryan Cronin, PPC Officer. Email rcc40@cam.ac.uk, Tel: 01223 338711.