Emergence of a Promiscuous Peroxidase Under Non-Equilibrium Conditions

In the far from equilibrium state of living matter, energy is consumed to fuel the metabolic networks of enzymatic reactions. The emergence of protometabolic pathways in primeval earth is intricately related to the evolutionary journey of modern enzymes. Fundamental understanding of such energy driven generation of early catalytic systems would help us recognize the conditions required for the minimal metabolism that predated the chemical emergence of life. Herein, we report substrate driven generation of a non-equilibrium catalytic machinery from a single amino acid functionalized fatty acid in presence of a cofactor hemin. The non-equilibrium assembled state showed acceleration of catalytic potential resulting in degradation of the substrate and subsequently led to disassembly. Controls that promoted equilibration could not access the three-dimensional microphases and showed substantially lower catalytic activity. Significantly, the assembled state showed latent catalytic function by hydrolysing a precursor to yield the same substrate. Consequently, the assembly was benefitted with augmented lifetime of the catalytic state exploiting a promiscuous cascade and thus foreshadowing protometabolism. The results contribute towards our understanding of energy driven generation of primitive catalytic machineries that assisted the minimal metabolism of early life.