Before proteins, metals acted as the earliest catalysts, initiating reactions resembling key metabolic processes1. In contrast, in modern biology, proteins are the primary catalytic agents and drive nearly all biochemical reactions2. Although contemporary enzymes are structurally complex, growing evidence suggests that they evolved from shorter, repeating sub-protein fragments, often referred to as “starter peptides”3. The evolutionary gap between simple metal-based prebiotic reactions and complex metabolic processes. To narrow this gap, we propose that metal-binding peptides acted as key intermediates prebiotic catalysis to the first enzymatic functions. To test our hypothesis, overall is to design a minimal metal-binding peptide and evolve it toward enzymatic activity. Here, we present the first step of this strategy: the in-silico design of a minimal metal-binding peptide.

Peer reviewed