title: Metabolic engineering of Corynebacterium glutamicum for L-arginine production.
abstract: L-arginine is an important amino acid for diverse industrial and health product applications. Here we report the development of metabolically engineered Corynebacterium glutamicum ATCC 21831 for the production of L-arginine. Random mutagenesis is first performed to increase the tolerance of C. glutamicum to L-arginine analogues, followed by systems metabolic engineering for further strain improvement, involving removal of regulatory repressors of arginine operon, optimization of NADPH level, disruption of L-glutamate exporter to increase L-arginine precursor and flux optimization of rate-limiting L-arginine biosynthetic reactions. Fed-batch fermentation of the final strain in 5 l and large-scale 1,500 l bioreactors allows production of 92.5 and 81.2 g l(-1) of L-arginine with the yields of 0.40 and 0.35 g L-arginine per gram carbon source (glucose plus sucrose), respectively. The systems metabolic engineering strategy described here will be useful for engineering Corynebacteria strains for the industrial production of L-arginine and related products.
authors.affiliation: 1] Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea [2] Daesang Corporation Research Center, Icheon-City, Gyeonggi-Do 467-813, Korea.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: 1] Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea [2] BioInformatics Research Center, KAIST, Daejeon 305-701, Korea.
authors.forename: Hyun Uk
authors.initials: HU
authors.lastname: Kim
authors.affiliation: 1] Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea [2] BioInformatics Research Center, KAIST, Daejeon 305-701, Korea.
authors.forename: Tae Yong
authors.initials: TY
authors.lastname: Kim
authors.affiliation: Daesang Corporation Research Center, Icheon-City, Gyeonggi-Do 467-813, Korea.
authors.forename: Jun Seok
authors.initials: JS
authors.lastname: Park
authors.affiliation: Daesang Corporation Research Center, Icheon-City, Gyeonggi-Do 467-813, Korea.
authors.forename: Suok-Su
authors.initials: SS
authors.lastname: Kim
authors.affiliation: 1] Metabolic and Biomolecular Engineering National Research Laboratory, Center for Systems and Synthetic Biotechnology, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Institute for the BioCentury, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea [2] BioInformatics Research Center, KAIST, Daejeon 305-701, Korea [3] BioProcess Engineering Research Center, KAIST, Daejeon 305-701, Korea.
authors.forename: Sang Yup
authors.initials: SY
authors.lastname: Lee
mesh_terms: D001120:Arginine / Q000096:biosynthesis* / Q000737:chemistry; D019149:Bioreactors; D002244:Carbon / Q000737:chemistry; D048230:Corynebacterium glutamicum / Q000378:metabolism*; D005285:Fermentation; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D005947:Glucose / Q000737:chemistry; D018698:Glutamic Acid / Q000378:metabolism; D007218:Industrial Microbiology; D060847:Metabolic Engineering / Q000379:methods*; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009249:NADP / Q000737:chemistry; D013395:Sucrose / Q000737:chemistry
chemical_list: D018698:Glutamic Acid; D009249:NADP; D013395:Sucrose; D002244:Carbon; D001120:Arginine; D005947:Glucose