Toward Photosynthetic Mammalian Cells through Artificial Endosymbiosis

Abstract Photosynthesis in plants occurs within specialized organelles known as chloroplasts, which are postulated to have originated through endosymbiosis with cyanobacteria. In nature, instances are also observed wherein specific invertebrates engage in symbiotic relationships with photosynthetic bacteria, allowing them to subsist as photoautotrophic organisms over extended durations. Consequently, the concept of engineering artificial endosymbiosis between mammalian cells and cyanobacteria represents a promising avenue for enabling photosynthesis in mammals. The study embarked with the identification of Synechocystis PCC 6803 as a suitable candidate for establishing a long‐term endosymbiotic relationship with macrophages. The cyanobacteria internalized by macrophages exhibited the capacity to rescue ATP deficiencies within their host cells under conditions of illumination. Following this discovery, a membrane‐coating strategy is developed for the intracellular delivery of cyanobacteria into non‐macrophage mammalian cells. This pioneering technique led to the identification of human embryonic kidney cells HEK293 as optimal hosts for achieving sustained endosymbiosis with Synechocystis PCC 6803. The study offers valuable insights that may serve as a reference for the eventual achievement of artificial photosynthesis in mammals.