Synthetic Gene Circuits Enable Escherichia coli To Use Endogenous H₂S as a Signaling Molecule for Quorum Sensing

Microorganisms often use specific autoinducers other than common metabolites for quorum sensing (QS). Herein, we demonstrated that Escherichia coli produced sulfide (H₂S, HS^-, and S^2-) with the concentrations proportionally correlated to its cell density. We then designed synthetic gene circuits that used H₂S as an autoinducer for quorum sensing. A sulfide/quinone oxidoreductase converted diffusible H₂S to indiffusible hydrogen polysulfide (HSH, n ≥ 2), and a gene regulator CstR sensed the latter to turn on the gene expression. We constructed three element libraries, with which 24 different circuits could be assembled for adjustable sensitivity to cell density. The H₂S-mediated gene circuits endowed E. coli cells within the same batch or microcolony with highly synchronous behaviors. Using them we successfully constructed cell factories capable of an autonomous switch from growth phase to production phase. Thus, these circuits provide a new tool-kit for metabolic engineering and synthetic biology.