Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA.
NSF-NASA Center for Chemical Evolution, Georgia Institute of Technology, Atlanta, GA, USA.
Nat Chem. 2022 Feb;14(2):170-178. doi: 10.1038/s41557-021-00878-w. Epub 2022 Feb 3.
Investigation of prebiotic metabolic pathways is predominantly based on abiotically replicating the reductive citric acid cycle. While attractive from a parsimony point of view, attempts using metal/mineral-mediated reductions have produced complex mixtures with inefficient and uncontrolled reactions. Here we show that cyanide acts as a mild and efficient reducing agent mediating abiotic transformations of tricarboxylic acid intermediates and derivatives. The hydrolysis of the cyanide adducts followed by their decarboxylation enables the reduction of oxaloacetate to malate and of fumarate to succinate, whereas pyruvate and α-ketoglutarate themselves are not reduced. In the presence of glyoxylate, malonate and malononitrile, alternative pathways emerge that bypass the challenging reductive carboxylation steps to produce metabolic intermediates and compounds found in meteorites. These results suggest a simpler prebiotic forerunner of today's metabolism, involving a reductive glyoxylate pathway without oxaloacetate and α-ketoglutarate-implying that the extant metabolic reductive carboxylation chemistries are an evolutionary invention mediated by complex metalloproteins.
研究前生物代谢途径主要基于非生物复制还原柠檬酸循环。虽然从简约的角度来看很有吸引力,但使用金属/矿物质介导的还原方法的尝试产生了复杂的混合物,反应效率低且不可控。在这里,我们表明氰化物可以作为一种温和且高效的还原剂,介导三羧酸中间产物和衍生物的非生物转化。氰化物加合物的水解随后脱羧使草酰乙酸还原为苹果酸,富马酸还原为琥珀酸,而丙酮酸和α-酮戊二酸本身不会被还原。在甘氨酸存在的情况下,出现了替代途径,可以绕过具有挑战性的还原羧化步骤,生成代谢中间产物和陨石中发现的化合物。这些结果表明,今天的代谢可能存在一个更简单的前生物前体,涉及一种还原的乙醛酸途径,而没有草酰乙酸和α-酮戊二酸——这意味着现存的代谢还原羧化化学是由复杂的金属蛋白介导的进化发明。
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