Development of a Quorum-Sensing Based Circuit for Control of Coculture Population Composition in a Naringenin Production System

As synthetic biology and metabolic engineering tools improve, it is feasible to construct more complex microbial synthesis systems that may be limited by the machinery and resources available in an individual cell. Coculture fermentation is a promising strategy for overcoming these constraints by distributing objectives between subpopulations, but the primary method for controlling the composition of the coculture of production systems has been limited to control of the inoculum composition. We have developed a quorum sensing (QS)-based growth-regulation circuit that provides an additional parameter for regulating the composition of a coculture over the course of the fermentation. Implementation of this tool in a naringenin-producing coculture resulted in a 60% titer increase over a system that was optimized by varying inoculation ratios only. We additionally demonstrated that the growth control circuit can be implemented in combination with a communication module that couples transcription in one subpopulation to the cell-density of the other population for coordination of behavior, resulting in an additional 60% improvement in naringenin titer.