Integration of systems biology with bioprocess engineering: L: -threonine production by systems metabolic engineering of Escherichia coli.
Random mutation and selection or targeted metabolic engineering without consideration of its impact on the entire metabolic and regulatory networks can unintentionally cause genetic alterations in the region, which is not directly related to the target metabolite. This is one of the reasons why strategies for developing industrial strains are now shifted towards targeted metabolic engineering based on systems biology, which is termed systems metabolic engineering. Using systems metabolic engineering strategies, all the metabolic engineering works are conducted in systems biology framework, whereby entire metabolic and regulatory networks are thoroughly considered in an integrated manner. The targets for purposeful engineering are selected after all possible effects on the entire metabolic and regulatory networks are thoroughly considered. Finally, the strain, which is capable of producing the target metabolite to a high level close to the theoretical maximum value, can be constructed. Here we review strategies and applications of systems biology successfully implemented on bioprocess engineering, with particular focus on developing L: -threonine production strains of Escherichia coli.
Lee
Sang Yup
SY
Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, KAIST, 335 Gwahangno, Yuseong-gu, Daejeon, 305-701, Republic of Korea, leesy@kaist.ac.kr.
Park
Jin Hwan
JH
D004926:Escherichia coli / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000502:physiology*; D023281:Genomics / Q000379:methods*; D060847:Metabolic Engineering / Q000379:methods*; D049490:Systems Biology / Q000379:methods*; D013912:Threonine / Q000096:biosynthesis* / Q000235:genetics*
D029968:Escherichia coli Proteins; D013912:Threonine