We applied elementary mode analysis to a recombinant metabolic network of carotenoid-producing E. coli in order to identify multiple-gene knockouts for an enhanced synthesis of the carotenoids diapolycopendial (DPL) and diapolycopendioic acid (DPA). Based on the model, all inefficient carotenoid biosynthesis pathways were eliminated in a strain containing a combination of eight gene deletions. To validate the model prediction, the designed strain was constructed and tested for its performance. The designed mutant produces the carotenoids at significantly increased yields and rates as compared to the wild-type. The consistency between model prediction and experimental results demonstrates that elementary mode analysis is useful as a guiding tool also for the rational strain design of more complex pathways for secondary metabolite production. © 2009 Elsevier Inc. All rights reserved.
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