Nonenzymatic Metabolic Reactions and Life’s Origins

Abstract

Prebiotic chemistry aims to explain how the biochemistry of life as we know it came to be. Most efforts in this area have focused on provisioning compounds of importance to life by multi-step synthetic routes that do not resemble biochemistry. However, gaining insight into why core metabolism uses the molecules, reactions, pathways, and overall organization that it does requires us to consider molecules not only as synthetic end goals. Equally important are the dynamic processes that build them up and break them down. This perspective has led many researchers to the hypothesis that the first stage of the origin of life began with the onset of a primitive non-enzymatic version of metabolism, initially catalyzed by naturally occurring minerals and metal ions. This view of life's origins has come to be known as "metabolism first". Continuity with modern metabolism would require a primitive version of metabolism to build and break down ketoacids, sugars, amino acids, and ribonucleotides in much the same way as the pathways that do it today. This review discusses metabolic pathways of relevance to the origin of life in a manner accessible to chemists, and summarizes experiments suggesting several pathways might have their roots in prebiotic chemistry. Finally, key remaining milestones for the protometabolic hypothesis are highlighted.

A way to thioacetate esters compatible with non-oxidative prebiotic conditions

“…It is noteworthy that no catalyst was used for the three steps www.nature.com/scientificreports/ www.nature.com/scientificreports/ from glyoxylate to thioester, outlining some intrinsic properties of these compounds to perform such reactions observed in the current metabolism. Over time this process may have improve with the introduction of catalysts, the first ones being probably simple minerals 36,37 , which were replaced by more elaborated metallic complexes, then proto-enzymes (probably proto-PFOR's), at a time when primitive co-enzymes already existed. CoA itself was probably introduced as early as this proto-PFOR stage as was thiamine pyrophosphate, still acting under a radical mechanism.…”

“…Over time this process may have improve with the introduction of catalysts, the first ones being probably simple minerals 36 , 37 , which were replaced by more elaborated metallic complexes, then proto-enzymes (probably proto-PFOR’s), at a time when primitive co-enzymes already existed. CoA itself was probably introduced as early as this proto-PFOR stage as was thiamine pyrophosphate, still acting under a radical mechanism.…”

In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes

“…The life of a cell appears as an entanglement of complex networks of synthesis and degradation of molecules in a dynamic equilibrium essential for its viability (Muchowska et al, 2020). Within the cell, metabolic networks are completely intertwined, leading to the generation of special domains.…”

Rethinking Life and Predicting Its Origin

“…Without a simple explanation for the phenomenon of life, those trying to recreate the origin of biological life have pursued divergent "worlds" and theories (18)(19)(20)(21). On one side there have been metabolism-first (22) advocates which attempt to reproduce extant biological metabolic pathways, particularly autocatalytic ones (23). Among the biggest obstacles to this approach has been the lack of catalytic specificity (24).…”