title: Construction of a Genome-Scale Metabolic Model of Arthrospira platensis NIES-39 and Metabolic Design for Cyanobacterial Bioproduction.
abstract: Arthrospira (Spirulina) platensis is a promising feedstock and host strain for bioproduction because of its high accumulation of glycogen and superior characteristics for industrial production. Metabolic simulation using a genome-scale metabolic model and flux balance analysis is a powerful method that can be used to design metabolic engineering strategies for the improvement of target molecule production. In this study, we constructed a genome-scale metabolic model of A. platensis NIES-39 including 746 metabolic reactions and 673 metabolites, and developed novel strategies to improve the production of valuable metabolites, such as glycogen and ethanol. The simulation results obtained using the metabolic model showed high consistency with experimental results for growth rates under several trophic conditions and growth capabilities on various organic substrates. The metabolic model was further applied to design a metabolic network to improve the autotrophic production of glycogen and ethanol. Decreased flux of reactions related to the TCA cycle and phosphoenolpyruvate reaction were found to improve glycogen production. Furthermore, in silico knockout simulation indicated that deletion of genes related to the respiratory chain, such as NAD(P)H dehydrogenase and cytochrome-c oxidase, could enhance ethanol production by using ammonium as a nitrogen source.
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 3-5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 3-5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.|Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Shimpei
authors.initials: S
authors.lastname: Aikawa
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 3-5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kojima
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Toya
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 3-5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.|Quantitative Biology Center, RIKEN, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Furusawa
authors.affiliation: Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 3-5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.|Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.|Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, 3-5 Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D064751:Ammonium Compounds / Q000378:metabolism; D001669:Biochemical Phenomena; D019149:Bioreactors / Q000382:microbiology*; D002952:Citric Acid Cycle / Q000502:physiology; D003576:Electron Transport Complex IV / Q000235:genetics; D000431:Ethanol / Q000378:metabolism*; D038181:FMN Reductase / Q000235:genetics; D055786:Gene Knockout Techniques; D016680:Genome, Bacterial / Q000235:genetics; D006003:Glycogen / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D010728:Phosphoenolpyruvate / Q000378:metabolism; D053545:Spirulina / Q000235:genetics / Q000378:metabolism*
chemical_list: D064751:Ammonium Compounds; D000431:Ethanol; D010728:Phosphoenolpyruvate; D006003:Glycogen; D038181:FMN Reductase; D003576:Electron Transport Complex IV