Synthetic Gene Circuits Enable To Use Endogenous HS as a Signaling Molecule for Quorum Sensing.

Microorganisms often use specific autoinducers other than common metabolites for quorum sensing (QS). Herein, we demonstrated that produced sulfide (HS, HS, and S) with the concentrations proportionally correlated to its cell density. We then designed synthetic gene circuits that used HS as an autoinducer for quorum sensing. A sulfide/quinone oxidoreductase converted diffusible HS to indiffusible hydrogen polysulfide (HSH, ≥ 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 HS-mediated gene circuits endowed 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.