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Kinetic Model of Tryptophan Synthesis

其他書名	Construction and Application
出版	University of California, San Diego, 2021
URL	http://books.google.com.hk/books?id=VQL-zgEACAAJ&hl=&source=gbs_api

註釋Tryptophan is a commodity chemical that poses an attractive target for fermentation, but its production is kept tightly controlled by metabolic and transcriptional control mechanisms. Different strain design interventions attempted to increase tryptophan titer, yield and productivity. In this study, a kinetic model of tryptophan synthesis in E. coli is constructed. The model consists of a set of mass action reactions corresponding to the mechanism of each enzyme within glycolysis, pentose phosphate, shikimate, and tryptophan synthesis pathways. This model was then perturbed to recreate the effects of strain design interventions in three case studies. First interventions used in a tryptophan producing strain were simulated, resulting in a 1.89 fold difference between final strain productivity and simulated productivity. Then two different sets of interventions from a study on the inhibitory effect of anthranilate on Indole-3-glycerol-phosphate synthase were simulated. Non-similarity was observed between the strain productivity and the model productivity for the first set of interventions, but the second set of interventions from the same study in a fed-batch set-up led to a final productivity of the model within twice the strain productivity. Finally, the effect of a feed rate profile on a tryptophan producing strain was examined, with overexpression found to dominate the effect of the feed rate profile. A 1.06 fold difference between the final simulated productivity value and the final actual productivity measurement was observed. This work demonstrates the potential of mass action kinetic models to replicate strain design experiments.