Researchers may have discovered the chemical spark that led to life on Earth.

A long-standing mystery in life sciences revolves around the transition from a chemical soup to the very first lifeforms. 

Researchers have hypothesised that a chemical reaction called phosphorylation may have been crucial for the assembly of three key ingredients in early life forms: short strands of nucleotides to store genetic information, short chains of amino acids (peptides) to do the main work of cells, and lipids to form encapsulating structures such as cell walls. 

However, no one has ever found a phosphorylating agent that was plausibly present on early Earth and could have produced these three classes of molecules side-by-side under the same realistic conditions, until now.

Chemists at The Scripps Research Institute (TSRI) have now identified just such a compound: diamidophosphate (DAP).

“We suggest a phosphorylation chemistry that could have given rise, all in the same place, to oligonucleotides, oligopeptides, and the cell-like structures to enclose them,” said Scripps researcher Dr Ramanarayanan Krishnamurthy.

“That in turn would have allowed other chemistries that were not possible before, potentially leading to the first simple, cell-based living entities.”

Their latest studies are part of an ongoing effort by scientists around the world to find plausible routes for the epic journey from pre-biological chemistry to cell-based biochemistry.

Other researchers have described chemical reactions involving different phosphorylating agents for different types of molecule, as well as different and often uncommon reaction environments.

“It has been hard to imagine how these very different processes could have combined in the same place to yield the first primitive life forms,” said Dr Krishnamurthy.

He and his team were able to show first that DAP could phosphorylate each of the four nucleoside building blocks of RNA in water or a paste-like state under a wide range of temperatures and other conditions.

With the addition of the catalyst imidazole, a simple organic compound that was itself plausibly present on the early Earth, DAP’s activity also led to the appearance of short, RNA-like chains of these phosphorylated building blocks.

Moreover, DAP with water and imidazole efficiently phosphorylated the lipid building blocks glycerol and fatty acids, leading to the self-assembly of small phospho-lipid capsules called vesicles—primitive versions of cells.

“With DAP and water and these mild conditions, you can get these three important classes of pre-biological molecules to come together and be transformed, creating the opportunity for them to interact together,” Dr Krishnamurthy said.

“It reminds me of the Fairy Godmother in Cinderella, who waves a wand and ‘poof,’ ‘poof,’ ‘poof,’ everything simple is transformed into something more complex and interesting.”

DAP’s importance in kick-starting life on Earth could be hard to prove several billion years after the fact, but Dr Krishnamurthy notes that key aspects of the molecule’s chemistry are still found in modern biology.

“DAP phosphorylates via the same phosphorus-nitrogen bond breakage and under the same conditions as protein kinases, which are ubiquitous in present-day life forms,” he said.

“DAP’s phosphorylation chemistry also closely resembles what is seen in the reactions at the heart of every cell’s metabolic cycle.”

The team now plans to follow these leads, and is consulting with with early-Earth geochemists to try to identify potential sources of DAP, or similarly acting phosphorus-nitrogen compounds, that were on the planet before life arose.