A set of biochemical processes crucial to cellular life on Earth
could have originated in chemical reactions taking place on the
early Earth four billion years ago, believes a group of scientists
from the Francis Crick Institute and the University of
Cambridge.
The researchers have demonstrated a network of chemical
reactions in the lab which mimic the important Krebs cycle present
in living organisms today. In a study published in the journal Nature Ecology and
Evolution, they say it could explain an important step in
how life developed on Earth.
Life developed four billion years ago on a harsh, volcanic
Earth that lacked any oxygen, but that did possess large oceans
rich in metal ions. There has been much interest in how the first
life forms developed in these conditions and how the biochemical
processes necessary to sustain life could form from
nothing.
Metabolism is universal to life. It's the set of processes
through which we gain energy from food and produce the biomolecules
we need in our body's cells. The biochemical pathways that underpin
these processes are highly similar across all organisms and
species.
One central metabolic pathway learned by every A-level
biology student is the Krebs cycle. But how did this essential set
of chemical reactions, each step catalyzed by an enzyme, first
arise? Each step in the cycle is not enough by itself. Life needs a
sequence of these reactions, and it would have needed it before
biological enzymes were around: Amino acids, the molecular
components of enzymes, are made from products of the Krebs
cycle.
Image: A primordial version of the Kreb's cycle could have
been sparked by sulphate particles on an early, volcanic Earth four
billion years ago.
The research group from the Francis Crick Institute and
the University of Cambridge say their demonstration offers an
answer. They have shown an enzyme-free metabolic pathway that
mirrors the Krebs cycle. It is sparked by particles called sulphate
radicals under conditions similar to those on Earth four billion
years ago.
Senior author Dr Markus Ralser of the Francis Crick
Institute and University of Cambridge explains: "This non-enzymatic
precursor of the Krebs cycle that we have demonstrated forms
spontaneously, is biologically sensible and efficient. It could
have helped ignite life four billion years ago."
The scientists used simple carbon compounds which are
involved at various points in the Krebs cycle (such compounds have
recently been found in a meteorite by NASA scientists) and mixed
them with iron and sulphur-containing chemicals that would be found
in sediments in the early oceans.
They carried out a systematic screening strategy of around
4,850 different experiments using mass spectrometry techniques, and
looked out for reactions similar to those seen in the Krebs
cycle.
In the vast majority of cases, the mixtures were
unreactive. However, in the presence of the compound
peroxydisulfate, the researchers detected 24 chemical reactions.
These resembled the pattern of reactions seen in the Krebs cycle in
living organisms.
"We took components representative of the sediments
present on Earth billions of years ago." says Dr Ralser, "As salts
that would have been present in the sediments did not trigger many
reactions, we mostly concentrated on metal ions and sulphate
species. These are also known to be important in the modern cell's
Krebs cycle.
"We conducted a huge screen involving thousands of
measurements then systematically worked through them. At the end we
found a condition that may have enabled the Krebs cycle to emerge.
It relies on sulphate radicals and previously nobody had thought
about them."
An alternative hypothesis for the origin of life suggests
that RNA - a molecule similar to DNA that can maintain genetic
information but is more transient and more reactive - can explain
the first steps towards life. This is known as the RNA-world
hypothesis.
Dr Ralser says: "There is a huge scientific debate about
whether the first steps towards life were driven by metabolism or
genetics."
He argues that the presence of RNA molecules cannot easily
explain the origin of metabolism, as RNA is made from products of
metabolism. And that his group's results support the theory that
environmental chemistry enabled metabolism to begin.
"People have tried to work on a non-enzymatic Krebs cycle
for years, but most have thought about it theoretically or
philosophically. Few have done systematic physical experiments like
those we report here. A non-enzymatic catalyst for the Krebs cycle
exists and we have found it," concludes Dr Ralser.