Crucial chemical for life can form in conditions found on early Earth

One of the most important molecules in living organisms has been synthesised from scratch under everyday conditions. The finding suggests that the chemical could have formed naturally early in our planet’s history and played a role in the origins of life.

The substance in question is called pantetheine. It isn’t a household name on the level of DNA or protein. However, pantetheine is the key component of a larger molecule called acetyl coenzyme A, a “cofactor” that helps enzymes to work.

“Coenzyme A is in every organism ever sequenced,” says Matthew Powner at University College London.

Powner has spent most of his career finding ways to make biological molecules from simple chemicals in ways that could have occurred naturally. In the past decade, he has shown that simple aminonitriles can be used to make nucleotides – the building blocks of DNA – and peptides, short versions of proteins.

His team has now shown that aminonitriles can be used to make pantetheine in a series of reactions starting with simple chemicals like formaldehyde. This took place in water, often at concentrations so dilute that the reaction mixtures looked like clear water. Sometimes the team used heat to speed things up, but otherwise didn’t need to intervene once the reactions were under way.

“It’s just all one pot – literally just throw it all in, don’t change anything, don’t do anything – and we get 60 per cent yield of our product,” says Powner.

Acetyl coenzyme A is involved in the synthesis of several biologically crucial chemicals. Some of the oldest groups of microorganisms use processes involving it to obtain carbon from the environment.

Crucially, pantetheine is the active part of the acetyl coenzyme A molecule. The other bit “isn’t essential to its function”, says Powner.

Cofactors of this sort are found in all living organisms. They have been described as remnants of life’s origin and early evolution.

“Obtaining any key organic biological cofactor from scratch” would be impressive, “let alone one of such central importance”, says Zachary Adam at the University of Wisconsin-Madison, who wasn’t involved in the research.

For Adam, the significance of the study goes beyond pantetheine and acetyl coenzyme A. “They are reporting this particular part of the cofactor, but the intermediates are being shown to be just as important,” he says. Other chemicals produced along the way have been shown to help make other biological molecules. “They’re building out this network of compounds.”

Many ideas about the origins of life have assumed that a small set of biological molecules formed long before the others. For instance, the “RNA world” hypothesis states that the first life was made solely of RNA, with other chemicals like proteins and lipids being added later once the RNA was capable of making them.

Powner is one of several researchers pushing for a different scenario, in which many key molecules formed early and interacted from the beginning. “All of these products can be a product of the same chemical reactions,” he says. Rather than starting with just RNA or just peptides, “it could be easier to make all of them together, and then the chemistries that they do are integrated from the origin”.