Life without phosphate – mystery solved?

Researchers say sulfur may hold the answer to a conundrum that has puzzled scientists for decades. Joel Hooper reports.

Untreated phosphate being offloaded at the Marca factory of the National Moroccan phosphates company. The chemical is vital to life but when the Earth was young most was locked up within stable minerals.

Scientists in Boston may have solved a longstanding mystery – how early life developed on an Earth where phosphate, a chemical so vital to a vast range of biological processes today, was unavailable.

Their work has led to an intriguing question – could an ancient sulfur-based metabolism have formed a key stepping stone towards life as we know it today?

Phosphate is essential to all modern life forms. From providing the backbone in DNA, to driving the cell’s energy currency in the form of the nucleotide adenosine triphosphate (ATP), phosphate is a key biological building block.

The chemical is so heavily involved in metabolism, the chemical reactions of life, that it is difficult to imagine life existing without it.

Yet, scientists believe that there was little phosphate readily available in the prebiotic soup in which life began.

It is a chicken-and-egg conundrum. The earth’s phosphate is largely locked up in stable minerals, and life forms such as bacteria must use complex enzymes to extract it in a useful form. But how could these enzymes evolve, without using phosphate?

To address this, the researchers used a theoretical approach known as “systems biology” to explore a phosphate-free metabolism.

A metabolic system like this might pre-date our earliest known ancestors and provide a pathway for life to emerge from readily available chemicals.

Their work was published is Cell.

The team led by Daniel Segrè began by assembling a large database of all known biochemical reactions from the earth’s entire biosphere.

Next, they removed all chemicals and reactions from their set which contained phosphate, or phosphorous in any form.

Then, starting with a “seed” set of eight chemicals that are thought to have been accessible to early life, they used computer simulations to began to look at how these simple molecules might react together to form new metabolites.

As new chemicals emerged from these reactions, the set grew larger, to include a connected network of 315 reactions and 260 metabolites – including 10 of the 20 amino acids which are used by modern cells to build proteins, as well as several ingredients by which cells metabolise sugars (a process known as the tricarboxylic acid (TCA) or Krebs cycle).

This new network of phosphate-free reactions was found to be rich in iron-sulfur clusters, supporting the idea that these readily available compounds could have been integral for the beginnings of life – the so-called “iron sulfur world hypothesis”.

The team also found that a type of sulfur-based compound called thioesters might have filled in some of the roles that phosphate plays in modern biochemistry.

When a sulfur-containing chemical called pantheteine was included in the set, along with a phosphate-free mechanism for electron transfer, the number of metabolites in the set exploded to include uracil and ribose, some of the key ingredients in RNA.

“Before our study, other researchers had proposed a sulfur-based early biochemistry, with hints that phosphate may not have been necessary until later,” noted lead author Segrè. “What was missing until now was data-driven evidence that these early processes, rather than scattered reactions, could have constituted a highly connected and relatively rich primitive metabolic network.”

This work, without providing direct experimental evidence, could potentially answer one of biology’s biggest mysteries. This phosphate-free biochemical blueprint allows us to imagine the missing link between the simple molecules of the pre-biotic earth and the phosphate-hungry organisms which populate our world today.

Joel Hooper is a senior research fellow at Monash University, in Melbourne, Australia.