Cost-Benefit Tradeoffs in Engineered lac Operons

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Science  18 May 2012:
Vol. 336, Issue 6083, pp. 911-915
DOI: 10.1126/science.1219083

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Accounting for Lac

When Escherichia coli expresses the lac operon, it needs to balance the potential increase in growth rate conferred through having the encoded proteins (which help it to take up and metabolize lactose) with the potential reduction in growth rate because of the resources needed to express and fold the encoded proteins. To investigate these inherent tradeoffs, Eames and Kortemme (p. 911) investigated the costs and benefits associated with the lac operon and surprisingly found that the main constraint on the system is not caused by the manufacture of the proteins themselves but by the lactose permease activity encoded by the LacY gene.


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.

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