Synthetic syntrophy for adenine nucleotide cross-feeding between metabolically active nanoreactors

Living systems depend on continuous energy input for growth, replication and information processing. Cells use membrane proteins as nanomachines to convert light or chemical energy of nutrients into other forms of energy, such as ion gradients or adenosine triphosphate (ATP). However, engineering sustained fuel supply and metabolic energy conversion in synthetic systems is challenging. Here, inspired by endosymbionts that rely on the host cell for their nutrients, we introduce the concept of cross-feeding to exchange ATP and ADP between lipid-based compartments hundreds of nanometres in size. One population of vesicles enzymatically produces ATP in the mM concentration range and exports it. A second population of vesicles takes up this ATP to fuel internal reactions. The produced ADP feeds back to the first vesicles, and ATP-dependent reactions can be fuelled sustainably for up to at least 24 h. The vesicles are a platform technology to fuel ATP-dependent processes in a sustained fashion, with potential applications in synthetic cells and nanoreactors. Fundamentally, the vesicles enable studying non-equilibrium processes in an energy-controlled environment and promote the development and understanding of constructing life-like metabolic systems on the nanoscale.