Logic Gates for Engineering Programmable Interactions in Microbial Consortia

The current state of synthetic biology relies heavily upon cultivation of single species of model microorganisms in tightly controlled laboratory environments. Such, often highly engineered, domesticated strains suffer from poor stability and resilience in natural settings due to fluctuating environmental conditions and competition from communities of indigenous microbes. To address these challenges, we have developed a generalizable framework for design and engineering of autonomous synthetic microbial consortia capable of operating safely within unpredictable and dynamic natural environments. At the center of the proposed platform lies photoautotroph-heterotroph interactive partnership. Such associations, which naturally assemble to take advantage of services carried out by individual members, are ubiquitous in nature and mediate key ecological processes such as energy capture, carbon fixation, and nutrient cycling. Genetically tractable photoautotrophic organisms, such as cyanobacteria, can sustain and drive an engineered consortium through production of O₂, organic C, and, in some cases, fixed inorganic or organic N. While metabolite exchange provides ways for functional compartmentalization, a tight control and a high level of communication and interaction between members of the consortium are required. As demonstrated in single-species models, computational logic gates provide a controllable and modular approach to programming desired cellular behavior. Applying logic gates so that output responses are sustained rather than transient to communities of bacteria, as opposed to single cells, will allow for more complex interactions and offers a novel way to precisely engineer synthetic multi-species systems. This presentation discusses opportunities for implementing logic-based controls into metabolically interdependent phototrophic consortia for improved communication, functional stability, and controllable output.