Predictive Mathematical Model for Polyhydroxybutyrate Synthesis in Escherichia coli


Angela Dixon

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MD5: 657822f21792043e634abc16f4f28535


Polyhydroxybutyrate has been studied as a potential biodegradable replacement for petrochemical plastics. Polyhydroxybutyrate synthesis is not native to Escherichia coli, but the genes have successfully been inserted through plasmids. However, polyhydroxybutyrate production needs to be more cost-effective before it can be commercially produced. A mathematical model for polyhydroxybutyrate synthesis was developed to identify genes that could be altered to increase polyhydroxybutyrate production. The major metabolic pathways included in the model were glycolysis, acetyl coenzyme-A synthesis, tricarboxylic acid cycle, glyoxylate bypass, and polyhydroxybutyrate synthesis. Reactions were modeled using kinetic mechanisms identified for each enzyme. The transcriptional network was incorporated into the model. The model was validated by comparison with published models and experimental polyhydroxybutyrate data. The predictive model identified two genes and one promoter as genetic engineering targets. Decreasing the substrate affinity of citrate synthase and glyceraldehyde-3-phosphate dehydrogenase, and increasing the activity of the lac promoter that regulates the polyhydroxybutyrate synthesis genes resulted in a 226.8% increase in total polyhydroxybutyrate production and a 275% increase in the rate of production.


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Dixon_2011_PHB_Predictive_Model.sbproj (360 kB)
MD5: 78add221597d4bc6d56418d64d5ce685