Discovering new chemical reactions from the ‘origins of life’ – Neuroscience News

Summary: Researchers have discovered a new set of chemical reactions that use cyanide, ammonia and carbon dioxide that generate amino acids and nucleic acids, the building blocks of proteins and DNA.

source: Scripps Research Institute

Four billion years ago, the Earth looked very different than it does today, devoid of life and covered in a vast ocean. Over millions of years, in that primordial soup, life appeared. Researchers have long theorized about how molecules combine to cause this transformation.

Now, scientists at Scripps Research have discovered a new set of chemical reactions that use cyanide, ammonia and carbon dioxide — all thought to be common in the early Earth — to generate amino acids and nucleic acids, the building blocks of proteins and DNA.

says Ramanarayanan Krishnamurthy, assistant professor of chemistry at Scripps Research and lead author of the new paper, which was published July 28, 2022 in the journal. nature chemistry.

“We think the type of reactions we’ve described are most likely what would have happened on early Earth.”

In addition to giving researchers insight into the chemistry of the early Earth, the newly discovered chemical reactions are also useful in some manufacturing processes, such as generating custom-labeled biomolecules from inexpensive starting materials.

Earlier this year, Krishnamurthy’s team demonstrated how cyanide can enable chemical reactions that convert prebiotic molecules and water into essential organic compounds required for life. In contrast to the previously proposed reactions, these reactions worked at room temperature and in a wide range of pH.

The researchers wondered whether, under the same conditions, there was a way to generate amino acids, the more complex molecules that make up the proteins in all known living cells.

In cells today, amino acids are created from precursors called alpha-keto acids using both nitrogen and specialized proteins called enzymes. Researchers have found evidence that alpha-keto acids may have existed early in Earth’s history.

However, many assumed that before the advent of cellular life, the amino acids must have been created from an entirely different precursor, aldehydes, rather than alpha-keto acids, because the enzymes needed to make the conversion did not yet exist.

But this idea has led to controversy over how and when the switch from aldehydes to alpha-keto acids occurred as a major component of making amino acids.

After successfully using cyanide to trigger other chemical reactions, Krishnamurthy and his colleagues suspected that cyanide, even without enzymes, might also help convert alpha-keto acids into amino acids. Knowing that 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 soon began to see the formation of amino acids.

“We were expecting it to be very difficult to figure out, and it turned out to be simpler than we had imagined,” says Krishnamurthy.

This shows the DNA in the person's hand
Now, scientists at Scripps Research have discovered a new set of chemical reactions that use cyanide, ammonia and carbon dioxide — all thought to be common in the early Earth — to generate amino acids and nucleic acids, the building blocks of proteins and DNA. The image is in the public domain 33

“If you just mix keto acid, cyanide, and ammonia, you’ll find it there. Once you add carbon dioxide, even tiny amounts, the speed of the reaction increases.”

Because the new reaction is relatively similar to what happens today inside cells — except that it is driven by cyanide rather than protein — it appears likely to be the source of early life, rather than radically different reactions, the researchers say.

The research also helps bring together two aspects of a long-running debate about the importance of carbon dioxide in early life, concluding that carbon dioxide was key, but only in combination with other molecules.

In the process of studying their chemical soup, Krishnamurthy’s team discovered that a byproduct of the reaction itself is a gradient, a precursor to the nucleotides that make up DNA and RNA. This suggests that the same primordial soup, under the right conditions, could have given rise to a large number of molecules necessary for the basic elements of life.

“What we want to do next is keep looking for the kind of chemistry that can emerge from this mixture,” Krishnamurthy says. Can amino acids start forming small proteins? Could one of these proteins go back and start acting as an enzyme to produce more of these amino acids? “

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In addition to Krishnamurthy, the authors of the study, “Prebiotic Synthesis of Alpha-Amino Acids and Orotate from α-Ketoacids Strengthens Transition to Existing Metabolic Pathways,” are Sunil Politikurti, Mahipal Yadav and Greg Springsteen.

This work was supported by funding from the NSF Center for Chemical Evolution (CHE-1504217), a NASA External Biology Grant (80NSSC18K1300) and a grant from the Simons Foundation (327124FY19).

About this genetic research news

author: press office
source: Scripps Research Institute
Contact: Press Office – Scripps Research Institute
picture: The image is in the public domain

original search: Access closed.
“Prebiotic synthesis of alpha-amino acids and orotate from alpha-keto acids promotes transition to existing metabolic pathways” by Ramanarayanan Krishnamurthy et al. nature chemistry


Summary

Prebiotic synthesis of alpha amino acids and orotate from alpha ketoacids promotes transition to existing metabolic pathways.

The Strecker interaction of aldehydes is the notable pathway to explain the prebiotic origins of alpha amino acids. However, biology uses the transfer of alpha-keto acids to synthesize amino acids that are then transformed into nucleic bases, implying an evolutionary switch – abiotic or biotic – for a prebiotic pathway that involves the Stryker reaction in current biosynthetic pathways.

Here we show that alpha-keto acids react with cyanide and ammonia sources to form the corresponding alpha-amino acids through the Bucherer-Berggs pathway. Effective conversion of a prebiotic from oxalo acetate to aspartate via n-Carbamoyl aspartate enables the simultaneous formation of dihydroerotate, in parallel with the biochemical synthesis of orotate as a precursor to a nucleopidine base. Glyoxylates form both glycine and orotate and react with malonate and urea to form aspartate and dihydroergotate.

These results, together with their previously demonstrated metabolic analogues of the Krebs cycle, suggest that there could be a natural emergence of ancestors of identical biological pathways with the possibility of a smooth transition from prebiotic chemistry to modern metabolism.

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