title: Systems Metabolic Engineering of Escherichia coli.
abstract: Systems metabolic engineering, which recently emerged as metabolic engineering integrated with systems biology, synthetic biology, and evolutionary engineering, allows engineering of microorganisms on a systemic level for the production of valuable chemicals far beyond its native capabilities. Here, we review the strategies for systems metabolic engineering and particularly its applications in Escherichia coli. First, we cover the various tools developed for genetic manipulation in E. coli to increase the production titers of desired chemicals. Next, we detail the strategies for systems metabolic engineering in E. coli, covering the engineering of the native metabolism, the expansion of metabolism with synthetic pathways, and the process engineering aspects undertaken to achieve higher production titers of desired chemicals. Finally, we examine a couple of notable products as case studies produced in E. coli strains developed by systems metabolic engineering. The large portfolio of chemical products successfully produced by engineered E. coli listed here demonstrates the sheer capacity of what can be envisioned and achieved with respect to microbial production of chemicals. Systems metabolic engineering is no longer in its infancy; it is now widely employed and is also positioned to further embrace next-generation interdisciplinary principles and innovation for its upgrade. Systems metabolic engineering will play increasingly important roles in developing industrial strains including E. coli that are capable of efficiently producing natural and nonnatural chemicals and materials from renewable nonfood biomass.
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Kyeong Rok
authors.initials: KR
authors.lastname: Choi
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Jae Sung
authors.initials: JS
authors.lastname: Cho
authors.affiliation: Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Dongsoo
authors.initials: D
authors.lastname: Yang
authors.affiliation: BioInformatics Research Center, KAIST, Daejeon 34141, Republic of Korea BioProcess Engineering Research Center, KAIST, Daejeon 34141, Republic of Korea Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, Daejeon 34141, Republic of Korea.
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
mesh_terms: D056804:Biofuels; D018533:Biomass; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D019143:Evolution, Molecular; D058025:Interdisciplinary Studies; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics; D058615:Synthetic Biology / Q000379:methods; D049490:Systems Biology / Q000379:methods*
chemical_list: D056804:Biofuels