Harrison Stuart A, Webb William L, Rammu Hanadi, Lane Nick
Centre for Life's Origins and Evolution (CLOE), Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
Life (Basel). 2023 May 12;13(5):1177. doi: 10.3390/life13051177.
A protometabolic approach to the origins of life assumes that the conserved biochemistry of metabolism has direct continuity with prebiotic chemistry. One of the most important amino acids in modern biology is aspartic acid, serving as a nodal metabolite for the synthesis of many other essential biomolecules. Aspartate's prebiotic synthesis is complicated by the instability of its precursor, oxaloacetate. In this paper, we show that the use of the biologically relevant cofactor pyridoxamine, supported by metal ion catalysis, is sufficiently fast to offset oxaloacetate's degradation. Cu-catalysed transamination of oxaloacetate by pyridoxamine achieves around a 5% yield within 1 h, and can operate across a broad range of pH, temperature, and pressure. In addition, the synthesis of the downstream product β-alanine may also take place in the same reaction system at very low yields, directly mimicking an archaeal synthesis route. Amino group transfer supported by pyridoxal is shown to take place from aspartate to alanine, but the reverse reaction (alanine to aspartate) shows a poor yield. Overall, our results show that the nodal metabolite aspartate and related amino acids can indeed be synthesised via protometabolic pathways that foreshadow modern metabolism in the presence of the simple cofactor pyridoxamine and metal ions.
一种关于生命起源的原代谢方法假定，代谢中保守的生物化学与前生物化学具有直接的连续性。现代生物学中最重要的氨基酸之一是天冬氨酸，它是许多其他必需生物分子合成的节点代谢物。天冬氨酸的前生物合成因其前体草酰乙酸的不稳定性而变得复杂。在本文中，我们表明，在金属离子催化的支持下，使用与生物相关的辅因子吡哆胺，其反应速度足够快，足以抵消草酰乙酸的降解。铜催化吡哆胺对草酰乙酸的转氨作用在1小时内可达到约5%的产率，并且可以在广泛的pH、温度和压力范围内进行。此外，下游产物β-丙氨酸的合成也可能在同一反应体系中以非常低的产率发生，直接模拟了古细菌的合成途径。由吡哆醛支持的氨基转移反应显示从天冬氨酸转移到丙氨酸，但逆向反应（从丙氨酸到天冬氨酸）的产率很低。总体而言，我们的结果表明，在简单的辅因子吡哆胺和金属离子存在的情况下，节点代谢物天冬氨酸和相关氨基酸确实可以通过预示现代代谢的原代谢途径合成。
