Prebiotic Synthesis of Aspartate Using Life's Metabolism as a Guide.

Prebiotic Synthesis of Aspartate Using Life's Metabolism as a Guide.
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使用生命代谢作为指导的天冬氨酸的益生元合成。

DOI:
10.3390/life13051177
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发表时间:
2023-05-12
期刊:
Life (Basel, Switzerland)
影响因子:
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生命起源的蛋白质代谢方法假设代谢的保守生物化学与生命前化学有直接的连续性。现代生物学中最重要的氨基酸之一是天冬氨酸,它是合成许多其他必需生物分子的节点代谢物。天冬氨酸的益生元合成由于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,使用生物相关的辅因子吡哆胺,支持金属离子催化,是足够快,以抵消草酰乙酸的降解。通过吡哆胺的草酰乙酸的Cu 2+催化的转氨基作用在1小时内达到约5%的产率,并且可以在宽的pH、温度和压力范围内操作。此外,下游产物β-丙氨酸的合成也可以在相同的反应系统中以非常低的产率进行,直接模拟古细菌合成途径。吡哆醛支持的氨基转移显示从天冬氨酸到丙氨酸发生,但逆反应(丙氨酸到天冬氨酸)显示产率很低。总体而言,我们的研究结果表明,节点代谢物天冬氨酸和相关的氨基酸确实可以合成通过蛋白代谢途径,预示着现代代谢的存在下,简单的辅因子吡哆胺和金属离子。
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. Cu2+-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.
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