Scientists uncover missing link in the Chemistry of Life

Study demonstrates that just a handful of "forgotten" biochemical reactions are needed to transform simple geochemical compounds into the complex molecules of life

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In a groundbreaking study, scientists have revealed a multibillion-year epic written into the chemistry of life, shedding light on the mysterious origins of life on Earth. The study, led by researchers from the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology and the California Institute of Technology (CalTech), demonstrates that just a handful of “forgotten” biochemical reactions are needed to transform simple geochemical compounds into the complex molecules of life.

The research, published in a recent scientific journal, delves into the idea that certain biochemical reactions crucial to the development of life may have been “forgotten” over time. The team of researchers, including Specially Appointed Associate Professors Harrison B. Smith and Liam M. Longo, Associate Professor Shawn Erin McGlynn from ELSI, and Research Scientist Joshua Goldford from CalTech, embarked on a quest to unravel the missing links in the history of biochemistry.

By investigating the earliest metabolic pathways on Earth, the researchers aimed to understand how simple geochemical molecules evolved into the complex biological molecules that sustain life today. They utilized an inventory of over 12,000 known biochemical reactions from the Kyoto Encyclopedia of Genes and Genomes database to model the stepwise development of metabolism.

Previous attempts to model the evolution of metabolism had failed to produce the most widespread, complex molecules used by contemporary life. However, the researchers discovered that a few compounds could be produced due to a “bottleneck” caused by the cell’s energy currency, adenosine triphosphate (ATP). They found that the reactions that form ATP themselves require ATP, creating a cyclic dependency that hindered the model’s progression.

Remarkably, the researchers identified a solution to this ATP bottleneck by modifying eight reactions to allow ATP-generating reactions to use polyphosphate instead of ATP. This simple adjustment enabled the model to achieve nearly all of contemporary core metabolism, providing crucial insights into the relative ages of common metabolites and the history of metabolic pathways.

One of the study’s most intriguing findings was the revelation that only eight new reactions, reminiscent of common biochemical reactions, are needed to bridge the gap between geochemistry and biochemistry. This discovery offers compelling evidence that even reactions that have gone extinct can be rediscovered from clues left behind in modern biochemistry.

The study’s lead researcher, Harrison B. Smith, remarked, “This does not prove that the space of missing biochemistry is small, but it does show that even reactions which have gone extinct can be rediscovered from clues left behind in modern biochemistry.”

The groundbreaking insights from this study provide a deeper understanding of the history of life on Earth and open new avenues for further exploration into the origins of biochemistry and the evolution of metabolic pathways.

This remarkable research is a testament to the relentless pursuit of knowledge and the unyielding curiosity of scientists striving to unlock the secrets of life’s ancient chemistry.

Journal Reference

  1. Goldford, J. E., Smith, H. B., Longo, L. M., Wing, B. A., & McGlynn, S. E. (2024). Primitive purine biosynthesis connects ancient geochemistry to modern metabolism. Nature Ecology & Evolution, 8(5), 999-1009. DOI: 10.1038/s41559-024-02361-4

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