Prebiotic Systems Chemistry: Complexity Overcoming Clutter

Abstract

SUMMARYLiving organisms are the most complex chemical system known to exist, yet exploit only a small constellation of universally conserved metabolites to support indefinite evolution. The conserved chemical simplicity belying biological diversity strongly indicates a unified origin of life. Thus, the chemical relationship between metabolites suggests that a simple set of predisposed chemical reactions predicated the appearance of life on Earth. Conversely, if prebiotic chemistry produces highly complex mixtures, this then implies that the feasibility of elucidating life's origins is an insurmountable task. Prebiotic systems chemistry, however, has recently been exploiting the chemical links between different metabolites to provide unprecedented scope for exploration of the origins of life, and an exciting new perspective on a 4 billion-year-old problem. At the heart of the systems approach is an understanding that individual classes of metabolites cannot be considered in isolation. This review highlights several recent advances suggesting that the canonical nucleotides and proteinogenic amino acids are predisposed chemical structures. KEYWORDSOrigins of life, prebiotic chemistry, systems chemistry, predisposed chemistry, RNA, nucleotides, amino acids, sugars, metabolism, crystallization. BIGGER PICTUREAdvancing our understanding of the spontaneous emergence of life requires innovation across scientific disciplines as broad as astrophysics to phylogenetics, yet the primacy of chemistry cannot be overestimated. Cellular life is a chemical system of awe-inspiring complexity yet, perhaps surprisingly, life exploits only a 2 small constellation of universally conserved metabolites working in concert to support indefinite evolution.The conserved chemical simplicity that belies biodiversity is a strong indication that a simple set of predisposed reactions predicated the sudden appearance of life on Earth. The wonder of nature's greatest feat of invention-the self-assembly of living cells-positions the origins of life as one of the greatest challenges in chemistry. Building chemical systems that can self-assemble, process information, control the transport and accumulation of chemicals, orchestrate reaction pathways, and ultimately self-replicate will no doubt have a major impact on evolving technology, but nature has had a 4 billion-year head start in implementing controlled chemical evolution, and the lessons to be learnt from its prior art merely await discovery. eTOCPrebiotic systems chemistry is providing unprecedented scope for exploring the origins of life and an exciting new perspective on a 4 billion-year-old problem. At the heart of this new systems approach is an understanding that individual classes of metabolites cannot be considered in isolation if the chemical origin of life on Earth is to be successfully elucidated. This review aims to highlight several recent advances that suggest the canonical nucleotides and proteinogenic amino acids are predisposed chemical structures.

Peptide ligation by chemoselective aminonitrile coupling in water

“…Our model unites prebiotic aminonitrile synthesis and biological a-peptides, suggesting short N-acyl peptide nitriles were plausible substrates during early evolution.To improve the efficiency and selectivity of peptide ligation in water we sought to develop a novel mechanism for non-enzymatic peptide synthesis, which would operate via biomimetic N®C ligation in near-neutral pH water, and we suspected that a combination of sulfur and nitrile chemistry would be required ( Fig. 1a) 8,9,14,[18][19][20][21] . Proteinogenic a-aminonitriles (AA-CN) are readily synthesised 8,18 , and their direct ligation would provide the simplest prebiotic pathway to peptides.…”

“…All investigated amino acids and their derivatives were coupled in good-to-excellent yields (Tables 1-3, Extended Data Table 4 & Extended Data Table 5). Sterically congested and b-branched thioacid ligations were also highly effective; ligations yielding Ac-Phe-Phe-CN, Ac-Phe-Val-CN and Ac-Val-Val-CN were all rapid and high yielding (Extended Data Table 5, entries [18][19][20]. We observed unprecedented protecting-group-free ligation for all 20 proteinogenic sidechain residues, including His, Asp, Lys, Cys, Ser, Thr and Tyr, which are all essential to enzyme catalysis, yet notoriously difficult to ligate under previously reported (prebiotic) conditions 2,4,30,32 .…”

Evidence of ammonium salts in comet 67P as explanation for the nitrogen depletion in cometary comae

“…Recent works have highlighted that ammonium salts reacting with glycol aldehyde can promote the formation of proteinogenic amino acids, while cyanamide reacting with glycol aldehyde results in the formation of natural nucleotide (33); (34). It is of great interest that these two key compounds (ammonium salts & cyanamide) are being detected together in the dust particles of 67P while glycol aldehyde is detected already in the undisturbed coma.…”

Autocatalytic Models for the Origin of Biological Homochirality

“…58 Indeed, this counterpoint has been seen as another "call to arms" 59 to synthetic organic chemists to participate more directly in the experimentally driven search for chemical reactions and networks that may give rise to the emergence of life. 60 It is upon this backdrop, focusing on ancient chemistry, that the subject of modern amino acid catalysis introduces the question of how complexity in organic reaction cycles may evolve.…”