Autonomous induction of recombinant proteins by minimally rewiring native quorum sensing regulon of E. coli.
Quorum sensing (QS) enables an individual bacterium's metabolic state to be communicated to and ultimately control the phenotype of an emerging population. Harnessing the hierarchical nature of this signal transduction process may enable the exploitation of individual cell characteristics to direct or "program" entire populations of cells. We re-engineered the native QS regulon so that individual cell signals (autoinducers) are used to guide high level expression of recombinant proteins in E. coli populations. Specifically, the autoinducer-2 (AI-2) QS signal initiates and guides the overexpression of green fluorescent protein (GFP), chloramphenicol acetyl transferase (CAT) and beta-galactosidase (LacZ). The new process requires no supervision or input (e.g., sampling for optical density measurement, inducer addition, or medium exchange) and represents a low-cost, high-yield platform for recombinant protein production. Moreover, rewiring a native signal transduction circuit exemplifies an emerging class of metabolic engineering approaches that target regulatory functions.
Tsao
Chen-Yu
CY
Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Hooshangi
Sara
S
Wu
Hsuan-Chen
HC
Valdes
James J
JJ
Bentley
William E
WE
D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006714:Homoserine / Q000031:analogs & derivatives; D007783:Lactones; D053038:Quorum Sensing / Q000235:genetics*; D011994:Recombinant Proteins / Q000378:metabolism; D018085:Regulon / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D007783:Lactones; C091088:N-octanoylhomoserine lactone; D011994:Recombinant Proteins; D006714:Homoserine; D001616:beta-Galactosidase