(67f) Tunable Synthetic Microbial Consortia: Foundations and Applications

Microbial symbiosis confers many advantages to its participants and has the potential to be utilized beyond naturally occurring communities. One application for this kind of synthetic consortium is the microbial production of molecules that are difficult to synthesize or may take many different steps and/or reactions to produce, such as biofuels or pharmaceuticals. Here we report the construction of a tunable synthetic microbial consortium created via the genetic engineering of E. coli auxotrophs to cross-feed and support each other when grown in co-culture. Genetic and metabolic circuits were designed to allow tunable control of the system via the export of essential amino acids by each of the auxotrophs. In this particular system, a tyrosine auxotroph (Δtyr) produces tryptophan for the tryptophan auxotroph (Δtrp) and vice versa. Inducible promoters are used to control the expression of relevant target genes, which then control the amino acid synthesis and export. It has been previously shown that the growth rate and composition of such a co-culture are determined by the export rate and cellular requirement of such essential molecules. By adding specific amounts of inducers we have been able to produce a gradient of target gene expression and a co-culture with a tunable growth rate and composition.

The relatively simple bacterial community mentioned above could be extended to a more complex inter-kingdom consortium consisting of a bacterium and a fungus, which has the potential to enable efficient and cost-effective cellulosic biofuel production. We have designed such a circuit based on quorum sensing, where the fungal member would produce bacterial signaling molecules that would allow it to control the growth of the bacterium. Through these molecules (the expression of which would be tuned exogenously) the fungus and bacterium would ?communicate? and be able to grow in a coordinated and tunable manner.