title: Fed-batch culture of Escherichia coli for L-valine production based on in silico flux response analysis.
abstract: We have previously reported the development of a 100% genetically defined engineered Escherichia coli strain capable of producing L-valine from glucose with a high yield of 0.38 g L-valine per gram glucose (0.58 mol L-valine per mol glucose) by batch culture. Here we report a systems biological strategy of employing flux response analysis in bioprocess development using L-valine production by fed-batch culture as an example. Through the systems-level analysis, the source of ATP was found to be important for efficient L-valine production. There existed a trade-off between L-valine production and biomass formation, which was optimized for the most efficient L-valine production. Furthermore, acetic acid feeding strategy was optimized based on flux response analysis. The final fed-batch cultivation strategy allowed production of 32.3 g/L L-valine, the highest concentration reported for E. coli. This approach of employing systems-level analysis of metabolic fluxes in developing fed-batch cultivation strategy would also be applicable in developing strategies for the efficient production of other bioproducts.
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering, BK21 Program, KAIST, Daejeon 305-701, Republic of Korea.
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Park
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005285:Fermentation; D005798:Genes, Bacterial; D007218:Industrial Microbiology / Q000379:methods*; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D049490:Systems Biology / Q000379:methods*; D014633:Valine / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; D014633:Valine; D019342:Acetic Acid