Communication and collaboration in synthetic microbial consortia

The biosynthesis of compounds of medical and industrial importance often requires engineering and optimization of complex metabolic pathways. Traditionally, these processes have employed a clonal population of recombinant microbes. There are many limitations of using a single population of microorganism that could be alleviated or addressed by using a mixed community, including metabolic load and the number of exogenous elements that can be cloned and optimized in a single cell. In order to control interactions required for these cells to work together, it is important to generate robust communication pathways between biotechnologically relevant species. To this end, we have developed a new set of transcriptional regulators and promoters based on the esa quorum-sensing system that can be used to turn gene expression on or off in response to a cell-cell communication signal. To expand our ability to use mixtures of diverse microbial species, we have developed a synthetic communication pathway between a representative Gram-negative organism (Escherichia coli) and representative Gram-postitive organism (Bacillus megaterium). An acyl-homoserine lactone (AHL)-dependent system was adapted to send signals from B. megaterium to E. coli. Components of a peptide-dependent microbial signaling pathway were used to send signals fromE. coli to B. megaterium. We anticipate that our communication system, when combined with strategies for fine-tuning ecological interactions, will be a key technology for the implementation of synthetic consortia for bioprocessing and metabolic engineering applications.