Light‐Driven Competitive Selection in a Protein‐Catalyzed Dissipative Peptide Replication

Theoretical models of prebiotic evolution propose that catalytic modulation can influence autocatalytic replication cycles. We hypothesized that a protein catalyst could create a favorable environment for proximity‐controlled, dissipative replication of primitive peptides. This setup, in principle, allows competitive selection by making the catalyst a limited resource. Here, we show that a structurally flexible and promiscuous protein, calmodulin, catalyzes UVA light‐driven replication in a helical foldamer‐based replicator system. The protein accelerates both non‐autocatalytic synthesis and autocatalytic replication, with autocatalysis being the dominant pathway. The system demonstrates light‐intensity‐dependent competitive selection, where replicators compete for scarce binding sites on the catalyst. This mechanism enables efficient selection even within a large replicator pool. Our results provide evidence that the specific catalyst–replicator interactions envisioned in Eigen's hypercycle model can be approximated under dissipative conditions in catalyzed primitive replicator systems.