TY - JOUR
T1 - Self-induced metabolic state switching by a tunable cell density sensor for microbial isopropanol production
AU - Soma, Yuki
AU - Hanai, Taizo
N1 - Funding Information:
We thank J. Hasty (University of California, San Diego) for providing the gene clock plasmid pTD103luxI/GFP, F. Matsuda (Osaka University) for measuring intracellular metabolites using LC-QqQ-MS and GC-Q-MS analysis, J. T. McEwen (University of California, Davis) for language help, and S. Atsumi (University of California, Davis) for helpful advice. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas ( 23119002 ) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) ; Grant-in-Aid for Creative Scientific Research ( 14J10450 ) from Japan Society for the Promotion of Science (JSPS) .
Publisher Copyright:
© 2015 International Metabolic Engineering Society.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/7/1
Y1 - 2015/7/1
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ymben.2015.04.005
DO - 10.1016/j.ymben.2015.04.005
M3 - Article
C2 - 25908185
AN - SCOPUS:84928753819
VL - 30
SP - 7
EP - 15
JO - Metabolic Engineering
JF - Metabolic Engineering
SN - 1096-7176
ER -