Emergence of a New Self-Replicator from a Dynamic Combinatorial Library Requires a Specific Pre-Existing Replicator

Abstract

Our knowledge regarding the early steps in the formation of evolvable life and what constitutes the minimal molecular basis of life remains far from complete. The recent emergence of systems chemistry reinvigorated the investigation of systems of self-replicating molecules to address these questions. Most of these studies focus on single replicators and the effects of replicators on the emergence of other replicators remains under-investigated. Here we show the cross-catalyzed emergence of a novel self-replicator from a dynamic combinatorial library made from a threonine containing peptide building block, which, by itself, only forms trimers and tetramers that do not replicate. Upon seeding of this library with different replicators of different macrocycle size (hexamers and octamers), we observed the emergence of hexamer replicator consisting of six units of the threonine peptide only when it is seeded with an octamer replicator containing eight units of a serine building block. These results reveal for the first time how a new replicator can emerge in a process that relies critically on the assistance by another replicator through cross-catalysis and that replicator composition is history dependent.

Guiding principles for peptide nanotechnology through directed discovery

“…147 For peptides, DCLs have been developed 139 using disulphide exchange of peptide components 149 that contain thiol groups, which can reversibly dimerize under reducing conditions thus forming a library of oligomeric species linked via S-S bonds. 150 For example, Otto and co-workers developed a DCL using reversible disulphide chemistry of macrocycles 151 with different size formed by threoninecontaining peptide functionalized dithiol, 152,153 where the product distribution shifts toward the self-assembling macrocycle.…”

Exploiting complexity to implement function in chemical systems

“…62 On the other hand, the appearance of some replicator molecules may require the presence of a pre-existing replicator, that is, in some cases the replicator itself does not form unless it is first templated by a previously formed oligomer. 63 Moreover, the emergence of parasitic behaviours of replicators that consume those members to which they owe their own formation has also been witnessed. 64 These dissimilar behaviours demonstrate the variety of possibilities that arise from studying complex systems.…”

Hydrogen-bonded host–guest systems are stable in ionic liquids

“…From these data, supramolecular chemists have established “reaction” patterns, much like in the early days of covalent chemistry. This noncovalent reactivity has already been used successfully to make some of the most outstanding synthetic architectures 6 , 7 , and even mimic some of life’s most fundamental features, like recognition and self-replication 8 . However, despite the enormous advances in supramolecular chemistry as a synthetic tool 9 , chemists still argue about the nature, or even the existence 10 , of particular intermolecular interactions.…”