Adaptive catalytic compartments emerge from synergistic integration of DNA nanostructures and transient coacervates

Biomolecular condensates formed via liquid–liquid phase separation (LLPS) are essential to cellular organization, catalysis, and regulation of biochemical pathways. Inspired by such natural systems, we present a new adaptive coacervate formed by multivalent salt-bridge interactions of polyhexamethylene biguanide (PHMB) polymer and adenosine triphosphate (ATP). These phase separated compartments efficiently sequester guanine-rich DNA sequences that adopt G-quadruplex (GQ) conformations in the presence of potassium ions. Hemin intercalates into these GQ structures to produce a catalytically active DNAzyme with amplified peroxidase-like activity. Within the coacervate, reduced molecular diffusion and increased local substrate concentrations synergistically augment the catalytic efficiency of the DNAzyme by 10-fold compared to that in the unconfined state. Integrating an enzymatic degradation cycle by alkaline phosphatase allows ATP-fueled dissipative behavior of the coacervates. By integrating self-assembling catalytic motifs within a dissipative host environment, this system demonstrates key principles of spatially and temporally regulated catalysis, mimicking features of cellular microreactors. Our work highlights the potential of synthetic LLPS-based platforms as tunable and compartmentalized catalytic systems, with implications for biomimetic reactor design and the development of advanced functional materials.