Characterizing a Propionate Sensor in E. coli Nissle 1917

Short-chain fatty acids (SCFAs) are commonly found inthe largeintestine, but generally not in the small intestine, and influencemicrobiome composition and host physiology. Thus, synthetic biologistsare interested in developing engineered probiotics capable of in situ detection of SCFAs as biogeography or disease sensors.One SCFA, propionate, is both sensed and consumed by E. coli. Here, we utilize the E. coli transcription factor PrpR, sensitiveto the propionate-derived metabolite (2S,3S)-2-methylcitrate, and its cognate promoter P-prpBCDE to detect extracellular propionate with the probiotic chassis bacterium E. coli Nissle 1917. We identify that PrpR-P-prpBCDE displays stationary phase leakiness and transient bimodality,and we explain these observations through evolutionary rationalesand deterministic modeling, respectively. Our results will help researchersbuild biogeographically sensitive genetic circuits.