Enantioselective Self-Replicators.

Self-replicating molecules provide a simple approach for investigating fundamental processes in scenarios of the emergence of life. Although homochirality is an important aspect of life and of how it emerged, the effects of chirality on self-replicators have received only little attention so far. Here, we report several self-assembled self-replicators with enantioselectivity that emerge spontaneously and grow only from enantiopure material. These require a relatively small number of chiral units in the replicators (down to eight) and in the precursors (down to a single chiral unit), compared to the only other enantioselective replicator reported previously. One replicator was found to incorporate material of its own handedness with high fidelity when provided with a racemic mixture of precursors, thus sorting (L)- and (D)-precursors into (L)- and (D)-replicators. Systematic studies reveal that the presence or absence of enantioselectivity depends on structural features (ring size of the replicator) that appear to impose constraints on its supramolecular organization. This work reveals new aspects of the little researched interplay between chirality and self-replication and represents another step toward the de novo synthesis of life.

Stochastic Emergence of Two Distinct Self-Replicators from a Dynamic Combinatorial Library.

Unraveling how chemistry can give rise to biology is one of the greatest challenges of contemporary science. Achieving life-like properties in chemical systems is therefore a popular topic of research. Synthetic chemical systems are usually deterministic: the outcome is determined by the experimental conditions. In contrast, many phenomena that occur in nature are not deterministic but caused by random fluctuations (stochastic). Here, we report on how, from a mixture of two synthetic molecules, two different self-replicators emerge in a stochastic fashion. Under the same experimental conditions, the two self-replicators are formed in various ratios over several repeats of the experiment. We show that this variation is caused by a stochastic nucleation process and that this stochasticity is more pronounced close to a phase boundary. While stochastic nucleation processes are common in crystal growth and chiral symmetry breaking, it is unprecedented for systems of synthetic self-replicators.

An Optical Probe for Real-Time Monitoring of Self-Replicator Emergence and Distinguishing between Replicators.

Self-replicating systems play an important role in research on the synthesis and origin of life. Monitoring of these systems has mostly relied on techniques such as NMR or chromatography, which are limited in throughput and demanding when monitoring replication in real time. To circumvent these problems, we now developed a pattern-generating fluorescent molecular probe (an ID-probe) capable of discriminating replicators of different chemical composition and monitoring the process of replicator formation in real time, giving distinct signatures for starting materials, intermediates, and final products. Optical monitoring of replicators dramatically reduces the analysis time and sample quantities compared to most currently used methods and opens the door for future high-throughput experimentation in protocell environments.

From self-replication to replicator systems en route to de novo life.

The process by which chemistry can give rise to biology remains one of the biggest mysteries in contemporary science. The de novo synthesis and origin of life both require the functional integration of three key characteristics - replication, metabolism and compartmentalization - into a system that is maintained out of equilibrium and is capable of open-ended Darwinian evolution. This Review takes systems of self-replicating molecules as starting points and describes the steps necessary to integrate additional characteristics of life. We analyse how far experimental self-replicators have come in terms of Darwinian evolution. We also cover models of replicator communities that attempt to solve Eigen's paradox, whereby accurate replication needs complex machinery yet obtaining such complex self-replicators through evolution requires accurate replication. Successful models rely on a collective metabolism and a way of (transient) compartmentalization, suggesting that the invention and integration of these two characteristics is driven by evolution. Despite our growing knowledge, there remain numerous key challenges that may be addressed by a combined theoretical and experimental approach.