Ter-Ovanessian Louis M P, Ryan Kate L, Shaarda Joshua, Stubbs R Trent, Krishnamurthy Ramanarayanan, Springsteen Greg
Department of Chemistry, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California, 92037, USA.
Department of Chemistry, Furman University, 3300 Poinsett Hwy, Greenville, South Carolina, 29613, USA.
Angew Chem Int Ed Engl. 2025 Jul;64(29):e202507248. doi: 10.1002/anie.202507248. Epub 2025 Jun 2.
α-Keto acids, such as pyruvate and glyoxylate, may have been critical in generating reaction networks at the origins of life due to their facile carbon-carbon bond formation and their hydrolytic stability. However, demonstrated prebiotic sources of these small α-keto acids have been limited by conditions required for their production, which are not conducive for subsequent incorporation or transition into (proto)metabolic pathways. Here, we demonstrate an abiotic generation of α-keto acids from only two amino acids, starting with the phosphorylation and dehydration of serine (Ser) coupled with a transamination with glycine (Gly), to produce both pyruvate and glyoxylate. This triggers an in situ reaction pathway producing higher-order α-keto acids, including amino acid precursors found in modern biology. These findings may help elucidate how protometabolic chemical networks can emerge on the early Earth under mild aqueous conditions, leading to a coupled amino acid-α-keto acid chemical system capable of supporting a more robust metabolism.
α-酮酸，如丙酮酸和乙醛酸，因其易于形成碳-碳键及其水解稳定性，可能在生命起源时生成反应网络中起着关键作用。然而，这些小α-酮酸已证实的益生元来源受到其产生所需条件的限制，这些条件不利于随后纳入或转变为（原）代谢途径。在此，我们展示了仅从两种氨基酸非生物生成α-酮酸的过程，起始于丝氨酸（Ser）的磷酸化和脱水，并与甘氨酸（Gly）进行转氨作用，以产生丙酮酸和乙醛酸。这触发了一条原位反应途径，生成更高级的α-酮酸，包括现代生物学中发现的氨基酸前体。这些发现可能有助于阐明在温和的水性条件下，原代谢化学网络如何在早期地球上出现，从而形成一个能够支持更强大代谢的耦合氨基酸-α-酮酸化学系统。
