title: Cost-benefit tradeoffs in engineered lac operons.
abstract: Cells must balance the cost and benefit of protein expression to optimize organismal fitness. The lac operon of the bacterium Escherichia coli has been a model for quantifying the physiological impact of costly protein production and for elucidating the resulting regulatory mechanisms. We report quantitative fitness measurements in 27 redesigned operons that suggested that protein production is not the primary origin of fitness costs. Instead, we discovered that the lac permease activity, which relates linearly to cost, is the major physiological burden to the cell. These findings explain control points in the lac operon that minimize the cost of lac permease activity, not protein expression. Characterizing similar relationships in other systems will be important to map the impact of cost/benefit tradeoffs on cell physiology and regulation.
authors.affiliation: Graduate Group in Biophysics, MC 2530, University of California, San Francisco, CA 94158-2330, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: Eames
authors.forename: Tanja
authors.initials: T
authors.lastname: Kortemme
mesh_terms: D001483:Base Sequence; D055162:Biocatalysis; D001692:Biological Transport; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D055786:Gene Knockout Techniques; D005818:Genetic Engineering; D007544:Isopropyl Thiogalactoside / Q000378:metabolism; D007763:Lac Operon; D056968:Lac Repressors; D007785:Lactose / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*; D001616:beta-Galactosidase / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D056968:Lac Repressors; C050221:LacY protein, E coli; D009004:Monosaccharide Transport Proteins; D027981:Symporters; D007544:Isopropyl Thiogalactoside; D001616:beta-Galactosidase; D007785:Lactose