Discovery of new chemical reactions “Origins of life”

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

Source: Scripps Research Institute

Four billion years ago, the Earth was very different from what it is today, devoid of life and covered by a vast ocean. Over millions of years, in this primordial soup, life has emerged. Researchers have long theorized how the molecules came together to trigger this transition.

Today, Scripps Research scientists have discovered a new set of chemical reactions that use cyanide, ammonia and carbon dioxide – all considered common on early Earth – to generate amino acids and nucleic acids, the building blocks of proteins and DNA.

“We have come up with a new paradigm to explain this shift from prebiotic chemistry to biotic chemistry,” says Ramanarayanan Krishnamurthy, PhD, associate professor of chemistry at Scripps Research and lead author of the new paper, published July 28, 2022 in the log natural chemistry.

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

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

Earlier this year, Krishnamurthy’s group showed how cyanide can activate chemical reactions that transform prebiotic molecules and water into the basic organic compounds needed for life. Unlike previously proposed reactions, this one worked at room temperature and over a wide pH range.

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

In cells today, amino acids are generated from precursors called α-keto acids using both nitrogen and specialized proteins called enzymes. The researchers found evidence that α-keto acids probably existed early in Earth’s history.

However, many have speculated that before the advent of cellular life, amino acids must have been generated from completely different precursors, aldehydes, rather than α-keto acids, since the enzymes to perform the conversion did not yet exist.

But this idea has led to a debate about how and when the switch from aldehydes to α-keto acids occurred as a key ingredient for making amino acids.

After successfully using cyanide to cause other chemical reactions, Krishnamurthy and his colleagues suspected that cyanide, even without enzymes, might also help turn α-keto acids into amino acids. Because they knew nitrogen would be needed in some form, they added ammonia, a form of nitrogen that would have been present on early Earth.

Then, through trial and error, they discovered a third key ingredient: carbon dioxide. With this mixture, they quickly began to see amino acids forming.

“We expected it to be quite difficult to figure this out, and it turned out to be even easier than we imagined,” says Krishnamurthy.

Today, Scripps Research scientists have discovered a new set of chemical reactions that use cyanide, ammonia and carbon dioxide – all considered common on early Earth – to generate amino acids and nucleic acids, the building blocks of proteins and DNA. Image is in public domain33

“If you just mix keto acid, cyanide, and ammonia, it stays there. As soon as you add carbon dioxide, even trace amounts, the reaction speeds up.

Because the new reaction is relatively similar to what happens inside cells today – except it’s driven by cyanide instead of protein – it seems more likely to be the source of the early of life, rather than radically different reactions, according to the researchers.

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

While studying their chemical soup, Krishnamurthy’s group discovered that a byproduct of the same reaction is orotate, 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 key elements of life.

“What we want to do next is continue to probe what kind of chemistry can emerge from this mix,” says Krishnamurthy. “Can amino acids start forming small proteins? Could one of these proteins come back and start acting like 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 α-amino acids and orotate from α-ketoacids potentiates the transition to existing metabolic pathways”, are Sunil Pulletikurti, Mahipal Yadav and Greg Springsteen.

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

About this genetic research news

Author: Press office
Source: Scripps Research Institute
Contact: Press Office – Scripps Research Institute
Image: Image is in public domain

Original research: Access closed.
“Prebiotic synthesis of α-amino acids and orotate from α-ketoacids potentiates transition to existing metabolic pathways” by Ramanarayanan Krishnamurthy et al. natural chemistry


Summary

Prebiotic synthesis of α-amino acids and orotate from α-ketoacids potentiates transition to existing metabolic pathways

The Strecker reaction of aldehydes is the preeminent pathway to explain the prebiotic origins of α-amino acids. However, biology uses transamination of α-ketoacids to synthesize amino acids which are then transformed into nucleobases, involving an evolutionary change – abiotic or biotic – from a prebiotic pathway involving the Strecker reaction into current biosynthetic pathways.

Here we show that α-keto acids react with cyanide and ammonia sources to form the corresponding α-amino acids via the Bucherer-Bergs pathway. Efficient prebiotic transformation of oxaloacetate into aspartate via NOT-carbamoyl aspartate allows the simultaneous formation of dihydroorotate, in parallel with the biochemical synthesis of orotate as a precursor of pyrimidine nucleobases. Glyoxylate forms both glycine and orotate and reacts with malonate and urea to form aspartate and dihydroorotate.

These results, together with previously demonstrated protometabolic analogues of the Krebs cycle, suggest that there may be a natural emergence of congruent precursors of biological pathways with the potential for a seamless transition from prebiotic chemistry to modern metabolism.

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