Characterizing a Propionate Sensor in E. coli Nissle 1917

Short-chain fatty acids (SCFAs) are commonly found in the large intestine, but generally not in the small intestine, and influence microbiome composition and host physiology. Thus, synthetic biologists are 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, sensitive to 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 rationales and deterministic modeling, respectively. Our results will help researchers build biogeographically sensitive genetic circuits.