A synthetic cell with integrated DNA self-replication and lipid biosynthesis

Abstract

Abstract The emergence, organization, and persistence of cellular life are the result of the functional integration of metabolic and genetic networks. Here, we engineer phospholipid vesicles that can operate three essential functions, namely transcription-translation of a partial genome, self-replication of this DNA program, and membrane synthesis. The synthetic genome encodes six proteins, and its compartmentalized expression produces active liposomes with distinct phenotypes demonstrating successful module integration. Our results reveal that genetic factors exert a stronger control over DNA replication and membrane synthesis than metabolic crosstalk or module co-activity. By showing how genetically encoded functions derived from different species can be integrated in liposome compartments, our work opens avenues for the construction of autonomous and evolving synthetic cells.