Monday, May 5, 2008
7-14

Systems metabolic engineering of Escherichia coli for L-threonine production

Kwang Ho Lee, Jin Hwan Park, Tae Yong Kim, Yu-Sin Jang, and Sang Yup Lee. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 program), BioProcess Engineering Research Center, Center for Systems and Synthetic Biotechnology, Department of BioSystems and Bioinformatics Research Center, Institute for the Biocentury, Korea Advanced Institute of Science and Technology (KAIST), 335 Gwahangno, Yuseong-gu, Daejeon, South Korea

Amino acid producers have traditionally been developed by repeated random mutagenesis owing to the difficulty in rationally engineering the complex and highly regulated metabolic network. By combined genome engineering, transcriptome analysis, and genome-scale metabolic flux analysis, we report the development of the first genetically-defined L-threonine (Thr) overproducing Escherichia coli strain. All known feedback inhibitions, transcriptional attenuation regulations, and those pathways that negatively affect Thr production were removed by genome engineering. Several target genes were identified by transcriptome profiling combined with flux response analysis, and were engineered accordingly. The final engineered E. coli strain was able to produce 82.4 g/l Thr by fed-batch culture. The strategy of systems metabolic engineering reported here can be employed for developing genetically-defined organisms for the efficient production of bioproducts. [This work was supported by the Korean Systems Biology Project of the Ministry of Science and Technology (M10309020000-03B5002-00000). Further supports by the LG Chem Chair Professorship and KOSEF through the CUPS are appreciated].

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