Department of Chemistry, Furman University, Greenville, SC, USA.
NSF-NASA Center for Chemical Evolution, Atlanta, GA, USA.
Nat Chem. 2020 Nov;12(11):1016-1022. doi: 10.1038/s41557-020-00560-7. Epub 2020 Oct 12.
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.
为了破译代谢途径的前生物根源，人们一直致力于再现现代生物转化，其中金属通常替代辅因子和酶发挥作用。在这里，我们展示了在温和的水相条件下，乙醛酸与丙酮酸反应可以在不需要金属或酶催化剂的情况下生成一系列还原性柠檬酸循环的α-酮酸类似物。这些转化与反向克雷布斯循环以相同的顺序进行，类似于原始代谢途径，其中乙醛酸既作为碳源又作为还原剂。此外，α-酮酸类似物通过与甘氨酸的转氨基作用提供了合成氨基酸的自然途径，与现有的代谢机制平行，并且避免了需要金属催化的非生物还原胺化作用。这种新兴的前生物反应序列可能为越来越复杂的在催化控制下运行的途径的出现奠定了基础。
