Biochemistry & Organic Chemistry

Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide

By Keith Cowing
Status Report
May 29, 2023
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Prebiotic Synthesis of Aspartate Using Life’s Metabolism as a Guide
Minimal autotrophic protometabolism. The network presents a chemically focused set of reactions which have universal or ancient conservation across all domains of life. The network is oriented around a pH gradient-catalysed CO2 fixation pathway with chemical similarity to the acetyl-CoA pathway and extends to the essential amino acids, nucleotides, and cofactors required in modern metabolisms. Major super-pathways have been colour-coded, and dashed lines represent pathways with poor conservation between bacterial and archaeal clades. — Life

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.

Stuart A. Harrison, William L. Webb, Hanadi Rammu and Nick Lane
Life 2023, 13(5), 1177; DOI: 10.3390/life13051177 (open access)
Astrobiology, Astrochemistry

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