title: Metabolic transistor strategy for controlling electron transfer chain activity in Escherichia coli.
abstract: A novel strategy to finely control a large metabolic flux by using a "metabolic transistor" approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its biosynthetic pathway. The change of the basal level of the essential component, considered as a base current in a transistor, has a large effect on the flux through the major pathway. In this way, the fine-tuning of a large flux can be accomplished. The "metabolic transistor" strategy was applied to control electron transfer chain function by manipulation of the quinone synthesis pathway in Escherichia coli. The achievement of a theoretical yield of lactate production under aerobic conditions via this strategy upon manipulation of the biosynthetic pathway of the key participant, ubiquinone-8 (Q8), in an E. coli strain provides an in vivo, genetically tunable means to control the activity of the electron transfer chain and manipulate the production of reduced products while limiting consumption of oxygen to a defined amount.
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, United States; State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, United States.
authors.forename: Leepika
authors.initials: L
authors.lastname: Tuli
authors.affiliation: Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, United States.
authors.forename: George N
authors.initials: GN
authors.lastname: Bennett
authors.affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, United States; Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX 77005, United States. Electronic address: ksan@rice.edu.
authors.forename: Ka-Yiu
authors.initials: KY
authors.lastname: San
mesh_terms: D045222:Electron Transport Chain Complex Proteins / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics*; D014451:Ubiquinone / Q000235:genetics / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D029968:Escherichia coli Proteins; D014451:Ubiquinone; D019344:Lactic Acid; C030778:ubiquinone 8
keywords: Electron transfer chain; Escherichia coli; Lactate; Metabolic transistor; Oxygen; Quinone