title: In silico screening of triple reaction knockout Escherichia coli strains for overproduction of useful metabolites.
abstract: For efficient production of industrially useful metabolites by microorganisms, it is important to design metabolic networks suitable for production. For this purpose, constraint-based metabolic flux simulation is a powerful tool to predict the effect of reaction knockouts on target productivity. In this study, using constraint-based metabolic simulation, in silico screening was performed to identify knockout candidate sets that increase the productivity of 1-butanol, 1-propanol, and 1,3-propanediol by engineered Escherichia coli. Metabolic changes caused by all possible sets of triple reaction knockouts were evaluated using a reduced metabolic model, which was constructed to significantly reduce the computational cost. The results demonstrated the strategies to improve target productivity by gene disruption; some of them could not be achieved by previous screening methods. Such knockout strategies can support further improvements of the target productivity.
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohno
authors.forename: Chikara
authors.initials: C
authors.lastname: Furusawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D020001:1-Butanol / Q000378:metabolism; D000433:1-Propanol / Q000378:metabolism; D019149:Bioreactors; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D005818:Genetic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D008954:Models, Biological; D011409:Propylene Glycols / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D011409:Propylene Glycols; C041787:1,3-propanediol; D020001:1-Butanol; D000433:1-Propanol