Synthetic syntrophy: A platform technology for adenine nucleotide cross-feeding between metabolically active vesicles

Abstract Living systems depend on a continuous input of energy for growth, replication, and information processing. Cells convert nutrients or light to form metabolic energy in the form of ion gradients and ATP. However, to install sustained fueling pathways in synthetic systems is challenging. Inspired by endosymbionts that rely on the host cell for their nutrients, we introduce the concept of cross-feeding between synthetic vesicles that can exchange ATP and ADP across their membranes. One population of vesicles produces and exports ATP, while a second population of vesicles takes up the ATP to fuel energy-consuming reactions. The produced ADP feeds back to the first vesicles. The vesicles are a new platform technology to fuel ATP-dependent processes in a sustained fashion, with wide 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.