Enhancing Intercellular Coordination: Rewiring Quorum Sensing Networks for Increased Protein Expression through Autonomous Induction.

While inducing agents are often used to redirect resources from growth and proliferation toward product outputs, they can be prohibitively expensive on the industrial scale. Previously, we developed an autonomously guided protein production system based on the rewiring of E. coli's native quorum sensing (QS) signal transduction cascade. Self-secreted autoinducer, AI-2, accumulated over time and actuated recombinant gene expression-its design, co-opting the collective nature of QS-mediated behavior. We recently demonstrated that desynchronization of autoinduced intercellular feedback leads to bimodality in QS activation. In this work, we developed a new QS-enabled system with enhanced feedback to reduce cell heterogeneity. This narrows the population distribution of protein expression, leading to significant per cell and overall increases in productivity. We believe directed engineering of cell populations and/or cell consortia will offer many such opportunities in future bioprocessing applications.