This deadly poison is the origin of all life

Before oxygen appeared on Earth, the environment was rife with cyanide. How did this deadly gas become a key ingredient in the emergence of life on Earth?

The topic of the origin of life has sparked endless debate and caused headaches for scientists and researchers. Although there are still scientific mysteries to be solved, we all agree that the world we know today was a very different place and made of very different materials when it was born 4.5 billion years ago. Oxygen, an element that is now essential for life, did not accumulate in the atmosphere until 2.33 billion years ago.

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So what was Earth's early atmosphere made of? Ironically, cyanide, a deadly poison, may have been a key ingredient for early life on Earth. Cyanide is widely believed to have been an important component of the primordial soup, the solution of organic compounds that gave rise to life.

A recent study led by chemists at Scripps Research in the United States has given us further insight into how early life may have survived Earth's toxic environment, and explains why other planets with similar environmental conditions may also support life to this day. The results of the study were published in Nature Chemistry.

In some suspense thriller movies, you may know that captured spies take cyanide pills to commit suicide. In fact, this fast-acting poison has a long history in many chemical forms. These substances are found in many plants and are highly toxic to humans whether inhaled as a gas, ingested in powder form or absorbed through topical contact.

Although cyanide is often associated with poison and death, scientists suspect that hydrogen cyanide (HCN), a gaseous cyanide, played an important role in the origin of life in the primordial soup. How is this possible? The answer is not as complicated as you might expect.

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Ramanarayanan Krishnamurthy, a chemist at the Scripps Research Institute in California, USA, gave us a quick refresher on the science of the origin of life. He believes that earlier forms of life may have been tolerant of cyanide because their chemical makeup was different from that of us and other organisms today. This suggests that substances that are toxic to us today would not have been toxic to early life on Earth.

Think of it this way: For humans, oxygen is not toxic, while carbon dioxide is, Krishnamurthy explained. But for plants and some animals with different chemical makeups, carbon dioxide, not oxygen, is their energy source. "We can infer that earlier life depended on cyanide, just as early life depended on carbon dioxide before oxygen appeared."

Once oxygen did form in Earth's atmosphere, life that couldn't adapt to it died out because it was toxic to them. But life that adapted to oxygen, or that performed oxygenic photosynthesis, continued to evolve. The same story happened with early life forms that relied on cyanide, Krishnamurthy said. They used the toxic chemical as an energy source, and once the cyanide ran out, they either changed to adapt to a different substance or died out completely.

Toxic primordial soup of life

Krishnamurthy and his team of chemists at the institute dug deeper into the subject, faithfully replicating molecules from early Earth and adding cyanide to the mix. One key feature of the experiment involved the "reductive tricarboxylic acid cycle," or r-TCA for short.

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Essentially, the complex biological processes we need to understand involve the use of proteins to form compounds that are necessary for life today. There was just one small problem with r-TCA back then. Remember that oxygen didn’t exist on early Earth? Neither did the proteins necessary for r-TCA to function. That’s why Krishnamurthy’s team used cyanide to conduct their experiments. They simulated alternative cyclic processes that could have formed the first compounds of life. The results showed that cyanide acts as a mild and effective reducing agent that mediates abiotic transformations of tricarboxylic acid intermediates and derivatives. The molecules in the experiment followed the same synthetic pathway as r-TCA does today.

While detailed experiments do provide a glimpse into what Earth's atmosphere looked like 4.5 billion years ago, there are still many questions about the origin of life that remain to be answered. Did life on Earth really begin with a dose of poison? Krishnamurthy speculates that if we want to solve this mystery, we must forget what life is like now and imagine going back to the early Earth 4.5 billion years ago. Here are some hints: comet flybys, volcanic eruptions, but no signs of human life. "We have to deal with any possible chemical reactions that could have occurred during that particular period," he said.

Origin of life science continues to advance, and as new research comes in we are adding new pieces to the puzzle, but there are still gaps to be filled.

Paper Information

【Title】Cyanide as a primordial reductant enables a protometabolic reductive glyoxylate pathway

【Journal】Nature Chemistry

【Author】Mahipal Yadav, Sunil Pulletikurti, Jayasudhan R. Yerabolu & Ramanarayanan Krishnamurthy

【Date】03 February 2022

【DOI】https://doi.org/10.1038/s41557-021-00878-w

【summary】

Investigation of prebiotic metabolic pathways is predominantly based on abiotically replicating the reductive citric acid cycle. While attractive from a parsimony point of view, attempts using metal/mineral-mediated reductions have produced complex mixtures with inefficient and uncontrolled reactions. Here we show that cyanide acts as a mild and efficient reducing agent mediating abiotic transformations of tricarboxylic acid intermediates and derivatives. The hydrolysis of the cyanide adducts followed by their decarboxylation enables the reduction of oxaloacetate to malate and of fumarate to succinate, whereas pyruvate and α-ketoglutarate themselves are not reduced. In the presence of glyoxylate, malonate and malononitrile, alternative pathways emerge that bypass the challenging reductive carboxylation steps to produce metabolic intermediates and compounds found in meteorites. These results suggest a simpler prebiotic forerunner of today's metabolism, involving a reductive glyoxylate pathway without oxaloacetate and α-ketoglutarate—implying that the extant metabolic reductive carboxylation chemistries are an evolutionary invention mediated by complex metalloproteins.

【Link】

https://www.nature.com/articles/s41557-021-00878-w

【Original link】

https://www.discovermagazine.com/the-sciences/born-to-die-how-life-on-earth-may-have-started-with-a-dose-of-poison

Source: Research Circle, Discover magazine

By Donna Sarkar

Translation: Ajin

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