Unravelling how the complexity of living systems can (have) emerge(d) from simple chemical reactions is one of the grand challenges in contemporary science.E volving systems of self-replicating molecules may hold the key to this question. Here we show that, when as ystem of replicators is subjected to ar egime where replication competes with replicator destruction, simple and fast replicators can give way to more complex and slower ones.T he structurally more complex replicator was found to be functionally more proficient in the catalysis of am odel reaction. These results show that chemical fueling can maintain systems of replicators out of equilibrium, populating more complex replicators that are otherwise not readily accessible.S uchc omplexification represents an important requirement for achieving open-ended evolution as it should allow improved and ultimately also new functions to emerge.
How life can emerge from inanimate matter is one of the grand challenges in contemporary science. Regardless of the approach to this challenge 1 , self-replicating systems 2-6 play a central role in the transition from chemistry to biology. While self-replication is a necessary condition for life, it is not a sufficient one. Functions beyond replication need to be acquired and assimilated in order for life to emerge 5,7 . The ability to catalyse reactions is one of the most essential of such functionalities and key to another central characteristic of life: metabolism. However, the mechanisms through which self-replicators can acquire catalytic and metabolic properties remain to be established 8,9 . Here we show how catalytic activity in a self-replicator emerges through co-option: features which are selected to benefit replication inadvertently result in an arrangement of chemical functionalities that is conducive to catalysis. Specifically, in a system of self-assembly driven self-replication, the assembly process generates the combination of a substrate-binding pocket and a catalytically active lysine residue. This configuration does not only enable the catalysis of a retro-aldol reaction with activities comparable to the best designer enzymes, but also the cleavage of FMOC groups with high efficiencies. Notably, the latter transformation liberates an alkene, which promotes the formation of molecules that replicators use for replication, thereby exerting a positive feedback on replication. Such chance invention of new function at the molecular level is essential for open-ended evolution and marks a pivotal step in the process by which replicators can acquire metabolic activity. The
Self-assembly features prominently in fields ranging from materials science to biophysical chemistry. Assembly pathways, often passing through transient intermediates, can control the outcome of assembly processes. Yet, the mechanisms of self-assembly remain largely obscure due to a lack of experimental tools for probing these pathways at the molecular level. Here, the self-assembly of self-replicators into fibers is visualized in real-time by high-speed atomic force microscopy (HS-AFM). Fiber growth requires the conversion of precursor molecules into six-membered macrocycles, which constitute the fibers. HS-AFM experiments, supported by molecular dynamics simulations, revealed that aggregates of precursor molecules accumulate at the sides of the fibers, which then diffuse to the fiber ends where growth takes place. This mechanism of precursor reservoir formation, followed by one-dimensional diffusion, which guides the precursor molecules to the sites of growth, reduces the entropic penalty associated with colocalizing precursors and growth sites and constitutes a new mechanism for supramolecular polymerization.
The conditions that led to the formation of the first organisms and the ways that life originates from a lifeless chemical soup are poorly understood. The recent hypothesis of “RNA-peptide coevolution” suggests that the current close relationship between amino acids and nucleobases may well have extended to the origin of life. We now show how the interplay between these compound classes can give rise to new self-replicating molecules using a dynamic combinatorial approach. We report two strategies for the fabrication of chimeric amino acid/nucleobase self-replicating macrocycles capable of exponential growth. The first one relies on mixing nucleobase- and peptide-based building blocks, where the ligation of these two gives rise to highly specific chimeric ring structures. The second one starts from peptide nucleic acid (PNA) building blocks in which nucleobases are already linked to amino acids from the start. While previously reported nucleic acid-based self-replicating systems rely on presynthesis of (short) oligonucleotide sequences, self-replication in the present systems start from units containing only a single nucleobase. Self-replication is accompanied by self-assembly, spontaneously giving rise to an ordered one-dimensional arrangement of nucleobase nanostructures.
The ability of molecules and systems to make copies of themselves and the ability of molecules to fold into stable, well-defined three-dimensional conformations are of considerable importance in the formation and persistence of life. The question of how, during the emergence of life, oligomerization reactions become selective and channel these reactions toward a small number of specific products remains largely unanswered. Herein, we demonstrate a fully synthetic chemical system where structurally complex foldamers and self-replicating assemblies emerge spontaneously and with high selectivity from pools of oligomers as a result of forming noncovalent interactions. Whether foldamers or replicators form depends on remarkably small differences in building block structures and composition and experimental conditions. We also observed the dynamic transformation of a foldamer into a replicator. These results show that the structural requirements/design criteria for building blocks that lead to foldamers are similar to those that lead to replicators. What determines whether folding or replication takes place is not necessarily the type of noncovalent interaction, but only whether they occur intra- or intermolecularly. This work brings together, for the first time, the fields of replicator and foldamer chemistry.
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