A Nonenzymatic Analog of Pyrimidine Nucleobase Biosynthesis

Metabolic theories for the origin of life posit that inorganic catalysts enabled self‐organized chemical precursors to the pathways of metabolism, including those that make genetic molecules. Recently, experiments showing nonenzymatic versions of a number of core metabolic pathways have started to s...

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Veröffentlicht in:Angewandte Chemie International Edition 2022-06, Vol.61 (23), p.e202117211-n/a
Hauptverfasser: Yi, Jing, Kaur, Harpreet, Kazöne, Wahnyalo, Rauscher, Sophia A., Gravillier, Louis‐Albin, Muchowska, Kamila B., Moran, Joseph
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Sprache:eng
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Zusammenfassung:Metabolic theories for the origin of life posit that inorganic catalysts enabled self‐organized chemical precursors to the pathways of metabolism, including those that make genetic molecules. Recently, experiments showing nonenzymatic versions of a number of core metabolic pathways have started to support this idea. However, experimental demonstrations of nonenzymatic reaction sequences along the de novo ribonucleotide biosynthesis pathways are limited. Here we show that all three reactions of pyrimidine nucleobase biosynthesis that convert aspartate to orotate proceed at 60 °C without photochemistry under aqueous conditions in the presence of metals such as Cu2+ and Mn4+. Combining reactions into one‐pot variants is also possible. Life may not have invented pyrimidine nucleobase biosynthesis from scratch, but simply refined existing nonenzymatic reaction channels. This work is a first step towards uniting metabolic theories of life's origin with those centered around genetic molecules. The biosynthetic reactions that convert aspartate into orotate, the precursor to pyrimidine nucleobases, occur nonenzymatically and without photochemistry at 60 °C in the presence of metals, giving insight into how these metabolic pathways may have emerged at the origin of life.
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202117211