An interdependent Metabolic and Genetic Network shows emergent properties in vitro

Abstract

A hallmark of all living organisms is their ability for self-regeneration which requires a tight integration of metabolic and genetic networks. Here we constructed a metabolic and genetic linked in vitro network (MGLN) that shows life-like behavior outside of a cellular context and generates its own building blocks from non-living matter. To this end, we integrated the metabolism of the crotonyl-CoA/ethyl-malonyl-CoA/hydroxybutyryl-CoA (CETCH) cycle with cell-free protein synthesis using recombinant elements (PURE). We demonstrate that the MGLN produces the essential amino acid glycine from inorganic carbon (CO2), and incorporates it into target proteins following DNA-encoded instructions. By programming genetically encoded response into metabolic networks our work opens new avenues for the development of advanced biomimetic systems with emergent properties, including decision-making, self-regeneration and evolution.