Efforts to decipher the prebiotic roots of metabolic pathways have focused on recapitulating modern biological transformations, with metals typically serving in place of cofactors and enzymes. Here we show that the reaction of glyoxylate with pyruvate under mild aqueous conditions produces a series of α-ketoacid analogues of the reductive citric acid cycle without the need for metals or enzyme catalysts. The transformations proceed in the same sequence as the reverse Krebs cycle, resembling a protometabolic pathway, with glyoxylate acting as both the carbon source and reducing agent. Furthermore, the α-ketoacid analogues provide a natural route for the synthesis of amino acids by transamination with glycine, paralleling the extant metabolic mechanisms and obviating the need for metal-catalysed abiotic reductive aminations. This emerging sequence of prebiotic reactions could have set the stage for the advent of increasingly sophisticated pathways operating under catalytic control.

破译代谢途径的生命起源根源的努力集中在概括现代生物转化，金属通常代替辅因子和酶。在这里，我们表明，乙醛酸与丙酮酸在温和的水性条件下反应产生一系列还原柠檬酸循环的α-酮酸类似物，而不需要金属或酶催化剂。这些转化按照与反向克雷布斯循环相同的顺序进行，类似于原代谢途径，乙醛酸既充当碳源又充当还原剂。此外，α-酮酸类似物提供了通过甘氨酸转氨基合成氨基酸的天然途径，与现有的代谢机制平行，并且消除了对金属催化的非生物还原胺化的需要。这种新兴的生命前反应序列可能为在催化控制下运行的日益复杂的途径的出现奠定了基础。