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. Author manuscript; available in PMC: 2013 Jan 3.
Published in final edited form as: Nat Rev Microbiol. 2012 Feb 27;10(4):291–305. doi: 10.1038/nrmicro2737

Figure 4. Principles of model-guided strain design.

Figure 4

(a) Non-growth-coupled production strains witness a decrease in product yield over time, while growth-coupled strains can enhance product yield. (b) Growth-coupled strain designs are predicted to force product secretion while growing optimally. Several methods have been developed to predict growth-coupled production strains by modeling reaction deletion, gene deletion, or reaction addition. Different reaction deletion algorithms, such as OptKnock68, Objective tilting69, and RobustKnock70 can provide different optimal growth-coupled strain designs, due to algorithmic differences. (d) Many algorithms predict the set of reactions that must be blocked to obtain a desired product. However, methods like OptGene71 and GDLS72, provide a more realistic view by modeling genetic modifications, since some genes catalyze multiple reactions, and other reactions are spontaneous.