Scientists Discover New “Origins of Life” Chemical Reactions

Abstract Biochemistry Origin of life Concept

“We think the kind of reactions we’ve described are probably what could have happened on early Earth,” says Ramanarayanan Krishnamurthy.

The reaction generates the building blocks of proteins and

Amino acids are a set of organic compounds used to build proteins. There are about 500 naturally occurring known amino acids, though only 20 appear in the genetic code. Proteins consist of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a shape that is biologically active. The amino acid sequences of proteins are encoded in the genes. Nine proteinogenic amino acids are called “essential” for humans because they cannot be produced from other compounds by the human body and so must be taken in as food.

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Four billion years ago, the Earth looked very different than it does today. It was devoid of life and covered by a vast ocean. Over the course of millions of years, life emerged in that primordial soup. For a long time, researchers have theorized how molecules came together to spark this transition. Now, scientists at Scripps Research have discovered a new set of chemical reactions that use ammonia, cyanide, and carbon dioxide—all thought to be common on the early Earth—to generate amino acids and nucleic acids, the building blocks of proteins and DNA.

“We’ve come up with a new paradigm to explain this shift from prebiotic to biotic chemistry,” says Ramanarayanan Krishnamurthy, PhD, and an associate professor of chemistry at Scripps Research. “We think the kind of reactions we’ve described are probably what could have happened on early Earth.” Krishnamurthy is the lead author of the new paper that was published in the journal Nature Chemistry on July 28, 2022.

In addition to giving scientists insight into the chemistry of the early Earth, the newly discovered chemical reactions are also useful in certain manufacturing processes. For example, in the generation of custom-labeled biomolecules from inexpensive starting materials.

Earlier this year, Krishnamurthy’s team showed how cyanide can enable the chemical reactions that turn prebiotic molecules and water into basic organic compounds required for life. This one worked at room temperature and in a wide pH range, unlike previously proposed reactions. The scientists themselves generate more complex amino acids whether under the proteins pose all the amino acids, which pose all known amino acids that with proteins living cells.

In cells today, amino acids are generated from precursors called α-keto acids using both nitrogen and specialized proteins called enzymes. Scientists have discovered evidence that α-keto acids likely existed early in Earth’s history. However, many researchers have hypothesized that before the advent of cellular life, amino acids must have been generated from completely different precursors, aldehydes, rather than α-keto acids, since enzymes to carry out the conversion did not yet exist. But that idea has led to debate about how and when the switch occurred from aldehydes to α-keto acids as the key ingredient for making amino acids.

After their success in using cyanide to drive other chemical reactions, Krishnamurthy’s group suspected that cyanide, even without enzymes, might also turn α-keto acids into amino acids. Because they knew nitrogen would be required in some form, they added ammonia—a form of nitrogen that would have been present on the early Earth. Then, through trial and error, they discovered a third key ingredient: carbon dioxide. With this mixture, they quickly started seeing amino acids form.

“We were expecting it to be quite difficult to figure this out, and it turned out to be even simpler than we had imagined,” says Krishnamurthy. “If you mix only the keto

In the process of studying their chemical soup, Krishnamurthy and his colleagues discovered that a byproduct of the same reaction is orotate, a precursor to nucleotides that make up DNA and

This work was supported by funding from the NSF Center for Chemical Evolution (CHE-1504217), the

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