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Establishing how life can emerge from inanimate matter is among the grand challenges of contemporary science. Chemical systems that capture life's essential characteristics-replication, metabolism and compartmentalization-offer a route to understanding this momentous process. The synthesis of life, whether based on canonical biomolecules or fully synthetic molecules, requires the functional integration of these three characteristics. Here we show how a system of fully synthetic self-replicating molecules, on recruiting a cofactor, acquires the ability to transform thiols in its environment into disulfide precursors from which the molecules can replicate. The binding of replicator and cofactor enhances the activity of the latter in oxidizing thiols into disulfides through photoredox catalysis and thereby accelerates replication by increasing the availability of the disulfide precursors. This positive feedback marks the emergence of light-driven protometabolism in a system that bears no resemblance to canonical biochemistry and constitutes a major step towards the highly challenging aim of creating a new and completely synthetic form of life.

Darwinian evolution, including the selection of the fittest species under given environmental conditions, is a major milestone in the development of synthetic living systems. In this regard, generalist or specialist behavior (the ability to replicate in a broader or narrower, more specific food environment) are of importance. Here we demonstrate generalist and specialist behavior in dynamic combinatorial libraries composed of a peptide‐based and an oligo(ethylene glycol) based building block. Three different sets of macrocyclic replicators could be distinguished based on their supramolecular organization: two prepared from a single building block as well as one prepared from an equimolar mixture of them. Peptide‐containing hexamer replicators were found to be generalists, i. e. they could replicate in a broad range of food niches, whereas the octamer peptide‐based replicator and hexameric ethyleneoxide‐based replicator were proven to be specialists, i. e. they only replicate in very specific food niches that correspond to their composition. However, sequence specificity cannot be demonstrated for either of the generalist replicators. The generalist versus specialist nature of these replicators was linked to their supramolecular organization. Assembly modes that accommodate structurally different building blocks lead to generalist replicators, while assembly modes that are more restrictive yield specialist replicators. [ABSTRACT FROM AUTHOR]