Positive Reinforcement

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Science  23 Apr 2010:
Vol. 328, Issue 5977, pp. 406
DOI: 10.1126/science.328.5977.406-b

It's often easier, when formulating rules, to tell people what not to do. Positively encouraging desirable behavior requires all manner of subtle distinctions that simple prohibitions avert. A similar contrast arises in efforts to direct the behavior of bacteria. Advances in genetic engineering have recently enabled researchers to modulate the internal chemistry of organisms such as Escherichia coli in order to favor excess production of a particular metabolite of commercial interest—a strategy prized for its chemical efficiency and waste minimization relative to synthetic elaboration of petroleum feedstocks. The modulation is straightforward when it entails deleting genes that disrupt the path to the desired product; determining which genes may need a boost is rather more complicated, given the interconnected nature of the cell's network of metabolic reactions. Choi et al. have developed a method of simulating metabolic flux for the express purpose of predicting which genes ought to be amplified in order to optimize production of a particular target compound. They demonstrate the method by optimizing for lycopene production in E. coli. Though not every gene identified in the simulation proved beneficial to amplify in practice, the method showed significant promise, particularly in tandem with a more traditional gene knockout simulation.

Appl. Environ. Microbiol. 76, 10.1128/AEM.00115-10 (2010).

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