Cybergenetic control of microbial community composition

The use of bacterial communities in bioproduction instead of monocultures has potential advantages including increased productivity through division of labour, ability to utilise cheaper substrates, and robustness against perturbations. A key challenge in the application of engineered bacterial communities is the ability to reliably control the composition of the community in terms of its constituent species. This is crucial to prevent faster growing species from outcompeting others with a lower relative fitness, and to ensure that all species are present at an optimal ratio during different steps in a biotechnological process. In contrast to purely biological approaches such as synthetic quorum sensing circuits or paired auxotrophies, cybergenetic control techniques - those in which computers interface with living cells-are emerging as an alternative approach with many advantages. The community composition is measured through methods such as fluorescence intensity or flow cytometry, with measured data fed real-time into a computer. A control action is computed using a variety of possible control algorithms and then applied to the system, with actuation taking the form of chemical (e.g., inducers, nutrients) or physical (e.g., optogenetic, mechanical) inputs. Subsequent changes in composition are then measured and the cycle repeated, maintaining or driving the system to a desired state. This review discusses recent and future developments in methods for implementing cybergenetic control systems, contrasts their capabilities with those of traditional biological methods of population control, and discusses future directions and outstanding challenges for the field.