(132f) Engineering Cellular Processes through Synthetic Membrane-Associated Biomolecular Condensates

Biomolecular condensates formed by liquid-liquid phase separation (LLPS) are increasingly being recognized as essential entities for organizing cellular processes. Despite this growing interest, relatively little is known about their roles on native membranes where many important functions such as transport, signal transduction, and metabolic reactions take place. To investigate LLPS and engineer the critical processes that take place on membranes, we took a synthetic biology approach by building artificial membrane-associated biomolecular condensates into film-like structures in the model organism Saccharomyces cerevisiae. We demonstrated the formation of synthetic condensates on intracellular membranes and recruitment of client proteins, thus turning these artificial structures into synthetic scaffolds capable of spatially organizing sets of proteins to perform designed functions. Focus of this work is on localized metabolic reactions of biotechnological interests to exploit the unique features of film-like condensates on membranes, where transport issues often arise at these physical boundaries between cellular compartments. We envision using these synthetic condensates both as a tool for investigating natural processes in the membrane local environment as well as engineering new functions on a host of metabolic engineering and synthetic biology applications.