Construction of a Genome-Scale Metabolic Model of Arthrospira platensis NIES-39 and Metabolic Design for Cyanobacterial Bioproduction

• Published in: PloS one 2015-12, Vol.10 (12), p.e0144430-e0144430
• Main Authors: Yoshikawa, Katsunori, Aikawa, Shimpei, Kojima, Yuta, Toya, Yoshihiro, Furusawa, Chikara, Kondo, Akihiko, Shimizu, Hiroshi
• Format: Article
• Language: English
• Subjects: Ammonium; Ammonium Compounds - metabolism; Anabaena variabilis; Analysis; Arthrospira; Biochemical Phenomena; Biomass; Bioreactors - microbiology; Biosynthesis; Carbon; Citric Acid Cycle - physiology; Computer simulation; Cyanobacteria; Cytochrome; Cytochrome-c oxidase; Design; Design engineering; E coli; Electron transport; Electron Transport Complex IV - genetics; Encyclopedias; Engineering schools; Escherichia coli; Ethanol; Ethanol - metabolism; FMN Reductase - genetics; Gene Knockout Techniques; Genes; Genetic engineering; Genome, Bacterial - genetics; Genomes; Genomics; Glycogen; Glycogen - metabolism; Industrial production; Information science; Metabolic engineering; Metabolic Engineering - methods; Metabolic flux; Metabolic Networks and Pathways - genetics; Metabolic Networks and Pathways - physiology; Metabolism; Metabolites; Models, Biological; NAD; NADPH dehydrogenase; Phosphoenolpyruvate - metabolism; Raw materials; Scale (ratio); Science; Simulation; Spirulina; Spirulina - genetics; Spirulina - metabolism; Spirulina platensis; Substrates; Synechococcus; Synechocystis; Tricarboxylic acid cycle
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144430

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.