CORE · Designer Condensates for Regulation of Catalytic Processes

Living cells have evolved to provide subcellular microenvironments that accommodate and control specific (bio)catalytic processes. These compartments include membrane-bound and membraneless organelles, or biomolecular condensates. New breakthroughs in studying and characterizing cellular biomolecular condensates have facilitated researchers to design synthetic condensates that are formed by liquid-liquid phase separation of engineered proteins, polypeptides, peptides, or nucleic acids. Yet, a precise regulation of designed condensates properties and their utilization for nanobiotechnological applications remains a major challenge. I propose to utilize my expertise in peptide design to develop libraries of synthetic condensates with systematically tunable chemical composition using minimalistic LLPS-promoting peptide building blocks. I will analyze how the chemical composition of condensates affect their physical and material properties and harness this knowledge to regulate organic reactions and drug synthesis in engineered microenvironments and develop condensates with emergent collective catalytic capacity. The proposed research will elucidate how the chemical composition, physical, and material properties of designed condensates affect reaction rate, conversion, and condensate reactivity. The designed condensates will go beyond the state of the art of synthetic nano- and microreactors and provide the next generation of reaction regulation for sustainable drug synthesis in organic solvent-free, aqueous environment. These findings will pave the way to establish novel design principles for the fabrication of synthetic condensates from peptide building blocks with both ordered and disordered motifs, leading to precise controlling, and balancing of these motifs to regulate reactivity effectively. I expect that this research will promote the LLPS, self-assembly, and nanobiotechnology communities for the development of condensates for emerging nanotechnologies.