Escherichia coli is widely used as a host cell for synthesis of valuable macromolecular products such as recombinant proteins. However, L colt has limited ability to secrete such macromolecules so that product harvest from the cells frequently requires chemical, enzymatic, and/or mechanical lysis, thus increasing production costs. In this study, we aimed to enable cell density-dependent auto-regulatory lysis in E. coil to directly aid in extraction of macromolecule products and simplify product harvest processes. Towards this aim, we designed and constructed a lysis genetic circuit based on a transducer-switch scheme by harnessing the characteristics of the stationary phase-operated carbon starvation promoter csiDp, the las quorum sensing regulatory unit, and the lytic protein colicin E7. Our transducer-switch lysis genetic circuit enabled: (i) lysis to be activated exclusively at stationary phase coupled with carbon starvation, which ensured that maximum cell growth was reached before product extraction; (ii) lysis-activating cell density to be controllable by varying input glucose amounts; and (iii) lysis performance to remain consistent independent of the amount of input glucose. Finally, we demonstrated the applicability of the lysis circuit to biotechnological applications by employing plasmid DNA extraction as a testbed. We envision that our novel genetic circuit, which conferred cell density dependent auto regulatory lysis, would serve as an economical, simplistic and environmentally friendly means for extraction of valuable macromolecules produced in E coli. (C) 2013 Elsevier Ltd. All rights reserved.