Sequence‐Modulated Active Tripeptide Condensates for Tandem Catalysis

Abstract

ABSTRACT Biomolecular condensates formed via liquid‐liquid phase separation function as dynamic organelles that are vital to regulating cellular activities. Peptide‐based coacervates have emerged as appealing candidates to resemble key properties of biomolecular condensates. However, their application as adaptive organelles has been hindered by structural complexity and limited control over phase‐separation. Here, we present short tripeptide coacervates with tunable phase‐separation behaviors governed by composition and peptide sequence, significantly reducing molecular complexity. These tripeptide condensates exhibit enzyme‐regulated phase‐separation, closely mimicking the dynamic nature of biomolecular condensates. A key attractive feature of the tripeptide coacervates is their capability to sequester both hydrophobic active species and hydrophilic enzymes. This unique property enables the execution of confined tandem reactions in aqueous conditions. When incorporated into membrane‐bound artificial cells, this tripeptide coacervates serve as adaptive sub‐organelles, orchestrating compartmentalized catalytic cascades. This work highlights the potential of minimalistic peptide systems as functional microreactors with biomimetic and catalytic capabilities.