Zimmermann Joris, Bora Basar Atalay, Moran Joseph
Institut de Science et d'Ingénierie Supramoléculaires (ISIS), CNRS UMR 7006, Université de Strasbourg, 8 Allée Gaspard Monge, 67000, Strasbourg, France.
Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, K1 N 6 N5, Canada.
Angew Chem Int Ed Engl. 2025 Jan 10;64(2):e202410698. doi: 10.1002/anie.202410698. Epub 2024 Dec 2.
Numerous reactions within metabolic pathways have been reported to occur nonenzymatically, supporting the hypothesis that life arose upon a primitive nonenzymatic precursor to metabolism. However, most of those studies reproduce individual transformations or segments of pathways without providing a common set of conditions for classes of reactions that span multiple pathways. In this study, we search across pathways for common nonenzymatic conditions for a recurring chemical transformation in metabolism: alkene hydration. The mild conditions that we identify (Fe oxides such as green rust) apply to all hydration reactions of the rTCA cycle and gluconeogenesis, including the hydration of phosphoenolpyruvate (PEP) to 2-phosphoglycerate (2PGA), which had not previously been reported under nonenzymatic conditions. Mechanistic insights were obtained by studying analogous substrates and through anoxic and radical trapping experiments. Searching for nonenzymatic conditions across pathways provides a complementary strategy to triangulate conditions conducive to the nonenzymatic emergence of a protometabolism.
据报道，代谢途径中的许多反应可非酶促发生，这支持了生命起源于原始非酶促代谢前体的假说。然而，这些研究大多只是重现单个转化反应或途径片段，并未为跨越多个途径的各类反应提供一套通用条件。在本研究中，我们在各途径中寻找代谢中一种反复出现的化学转化反应——烯烃水合反应的常见非酶促条件。我们确定的温和条件（如绿锈等铁氧化物）适用于还原性三羧酸循环（rTCA循环）和糖异生的所有水合反应，包括磷酸烯醇式丙酮酸（PEP）水合生成2-磷酸甘油酸（2PGA），此前在非酶促条件下尚未报道过该反应。通过研究类似底物以及进行缺氧和自由基捕获实验，获得了相关机理见解。跨途径寻找非酶促条件为确定有利于原代谢非酶促出现的条件提供了一种补充策略。
