Role of metal ions and their complexes in the catalysis of pertinent prebiotic reactions

Abstract

The first forms of cellular life (protocells) on the early Earth are posited to be a self-sustaining chemical system capable of Darwinian evolution, with primitive genetic polymers and metabolic reaction networks encapsulated in a membranous compartment. Given this, we first set out to investigate the formation and replication of RNA. This is thought to have been one of the first biomolecules to have emerged on the early Earth due to its intrinsic ability to both store and propagate information, and to facilitate catalysis of reactions. Previous studies have investigated the nonenzymatic oligomerization/replication of chemically activated nucleotides whose presence on the prebiotic Earth in significant amounts is debatable. Therefore, we evaluated the oligomerization of prebiotically relevant nucleotides i.e., cyclic nucleotides (cNMPs) and adenosine 5′ triphosphate (ATP). Both, cNMPs and ATP resulted in oligomers when subjected to repeated dry-wet cycles, a feature common on the early Earth just as it is today. Furthermore, we also tested the role of metal ions on these aforementioned processes by characterizing these reactions in hot spring water samples from Astrobiologically relevant sites in Ladakh, India. Subsequently, we investigated the ability of cNMPs to propagate genetic information in enzyme-free template-directed replication reactions. These reactions showed addition of intact nucleotides to the primer, which resulted in formation of longer informational polymers. In all, these studies underscored the relevance of both cNMPs and ATP to act as building blocks, in the formation and propagation of genetic information on the early Earth. In addition to the aforesaid, we were also keen on investigating transition metal ion-mediated oxidation reactions in the context of primitive metabolism. Few studies in the past showed free metal ions and select metal-complexes to catalyze certain prebiotically relevant reactions. Nonetheless, the transition from metal ions to extant metalloenzymes largely remains unclear. To unravel the plausible route, we evaluated the influence of biologically relevant porphyrin scaffold, on metal ion-mediated oxidation reactions. The presence of porphyrin was observed to modulate the catalytic activity of certain metal ions, highlighting the selective advantage that certain metal ions would have had in the presence of scaffolds like porphyrin. Altogether, our findings have helped to delineate aspects pertaining to the emergence and propagation of primitive genetic polymers, and minimal enzymes, thereby furthering the field’s insights on processes central to the emergence of early life.