Sourdough starter-inspired living materials grown from probiotic consortia with engineered division-of-labor

Synthetic genetic circuits, engineered networks of genetic components that perform user-defined logical functions in living cells, enable precise control over cellular behavior. As circuits become more complex to support sophisticated functions, implementing them within a single cell population becomes difficult. Tasks can instead be distributed among different populations in engineered consortia. However, selecting appropriate consortia and harnessing the natural traits of each species for such a division of labor remain unsolved challenges. Here, we report the creation of SINERGY, an engineered synthetic sourdough starter in which functional modules are distributed between the two constituent species. These modules, consisting of sensing, cross-kingdom communication, and response, enable in vitro biosensing and in vivo drug delivery and modulate the gut ecosystem in an animal disease model. SINERGY not only preserves the long-standing safety and health-promoting properties of the natural components but also endows symbiotic microbes with programmable functionalities, facilitating broad applications in biomedicine.