Executive Summary : | The evolution of modern-day enzymes is closely linked to the origin of metabolic pathways. Early enzymes involved in lipid, sugar, and amino acid metabolism played a crucial role in the minimal metabolism needed for protocellular life. Catalytic promiscuity, a latent ability of biocatalysts to facilitate multiple reactions with broadened substrate specificity, has been seen as a vestige in modern-day enzymes. Early biochemistry benefited from primitive promiscuous enzymes, which could process diverse biochemical reactions that could benefit other reactions in protometabolic networks. This versatility of early promiscuous catalytic systems also presents an opportunity for co-option for different functions. De novo designs of promiscuous enzymes have been attempted to target various chemical transformations, leading to applications in speciality chemicals and pharmaceutical industries. The earliest rudimentary protein folds are argued to be short peptides that can self-assemble in harsh situations to access paracrystalline folded structures. This study proposes exploring the assemblies of cross β amyloid-based short peptides that can demonstrate promiscuity to catalyze multiple metabolically important orthogonal chemical transformations and create a network that benefits connected transformations. The study aims to discover ways of designing promiscuous catalytic systems based on simple short peptide-based microphases, providing a fundamental understanding of early metabolic pathways and strategies for fine-tuning new to nature activities. |