Encoding Multiple Reactivity Modes within a Single Synthetic Replicator

Establishing programmable and self-sustaining
replication networks
in pools of chemical reagents is a key challenge in systems chemistry.
Self-replicating templates are formed from two constituent components with complementary
recognition and reactive sites via a slow bimolecular pathway and
a fast template-directed pathway. Here, we re-engineer one of the
components of a synthetic replicator to encode an additional recognition
function, permitting the assembly of a binary complex between the
components that mediates replicator formation through a template-independent
pathway, which achieves maximum rate acceleration at early time points
in the replication process. The complementarity between recognition
sites creates a key conformational equilibrium between the catalytically
inert product, formed via the template-independent pathway, and the
catalytically active replicator that mediates the template-directed
pathway. Consequently, the rapid formation of the catalytically inert
isomer kick-starts replication through the template-directed pathway.
Through kinetic analyses, we demonstrate that the presence of the
two recognition-mediated reactivity modes results in enhanced template
formation in comparison to that of systems capable of exploiting only
a single recognition-mediated pathway. Finally, kinetic simulations
reveal that the conformational equilibrium and both the relative and
absolute efficiencies of the recognition-mediated pathways affect
the extent to which self-replicating systems can benefit from this
additional template-independent reactivity mode. These results allow
us to formulate the rules that govern the coupling of replication
processes to alternative recognition-mediated reactivity modes. The
interplay between template-directed and template-independent pathways
for replicator formation has significant relevance to ongoing efforts
to design programmable and adaptable replicator networks.