Programmable short peptide condensates with intrinsic enzyme-like activity

Abstract

the co-assembly of short peptides. We find that mixing the histidine-tagged short peptides with triphenylalanine-based peptides leads to the formation of a stable coacervate phase, in contrast to the rigid aggregates formed by each individual component. This cooperative assembly enables the generation of functional coacervate compartments with built-in catalytic capability. The resulting peptide coacervates exhibit selective partitioning and sequestration of hydrophobic substrates, thereby enhancing local substrate concentration and promoting catalytic hydrolysis reactions. Our results demonstrate that catalytic activity can be encoded directly into coacervate-forming building blocks through rational peptide design, providing a versatile platform for programming LLPS behavior and constructing biomimetic active materials with potential applications in synthetic biology.