title: Self-induced metabolic state switching by a tunable cell density sensor for microbial isopropanol production.
abstract: Chemicals production by engineered microorganisms often requires induction of target gene expression at an appropriate cell density to reduce conflict with cell growth. The lux system in Vibrio fischeri is a well-characterized model for cell density-dependent regulation of gene expression termed quorum sensing (QS). However, there are currently no reports for application of the lux system to microbial chemical production. Here, we constructed a synthetic lux system as a tunable cell density sensor-regulator using a synthetic lux promoter and a positive feedback loop in Escherichia coli. In this system, self-induction of a target gene expression is driven by QS-signal, and its threshold cell density can be changed depending on the concentration of a chemical inducer. We demonstrate auto-redirection of metabolic flux from central metabolic pathways toward a synthetic isopropanol pathway at a desired cell density resulting in a significant increase in isopropanol production.
authors.affiliation: Laboratory for Bioinformatics, Graduate School of Systems Biosciences, Kyushu University, 804 Westwing, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Soma
authors.affiliation: Laboratory for Bioinformatics, Graduate School of Systems Biosciences, Kyushu University, 804 Westwing, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: taizo@brs.kyushu-u.ac.jp.
authors.forename: Taizo
authors.initials: T
authors.lastname: Hanai
mesh_terms: D019840:2-Propanol / Q000378:metabolism*; D048908:Aliivibrio fischeri / Q000235:genetics / Q000378:metabolism; D019149:Bioreactors / Q000382:microbiology*; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development*; D015964:Gene Expression Regulation, Bacterial
chemical_list: D019840:2-Propanol
keywords: Metabolic engineering; Metabolic flux redirection; Quorum sensing; Synthetic genetic circuit; Synthetic metabolic pathway; lux system