Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, Université de Strasbourg, 8 Allée Gaspard Monge, 67000, Strasbourg, France.
Institut Universitaire de France (IUF), France.
Angew Chem Int Ed Engl. 2022 Jun 7;61(23):e202117211. doi: 10.1002/anie.202117211. Epub 2022 Apr 5.
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 Cu and Mn . 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.
生命起源的代谢理论假设，无机催化剂使代谢途径的自组织化学前体，包括那些制造遗传分子的前体得以实现。最近，一些核心代谢途径的非酶版本的实验已经开始支持这一观点。然而，沿着从头核苷酸生物合成途径的非酶反应序列的实验证明是有限的。在这里，我们表明，在存在铜和锰等金属的水相条件下，天冬氨酸转化为乳清酸盐的嘧啶核苷碱基生物合成的所有三个反应都可以在 60°C 下进行，而无需光化学。将反应组合成一锅法变体也是可能的。生命可能不是从头开始发明嘧啶核苷碱基生物合成，而是简单地改进现有的非酶反应通道。这项工作是将生命起源的代谢理论与围绕遗传分子的理论结合起来的第一步。
