title: Enhanced recombinant protein productivity by genome reduction in Bacillus subtilis.
abstract: The emerging field of synthetic genomics is expected to facilitate the generation of microorganisms with the potential to achieve a sustainable society. One approach towards this goal is the reduction of microbial genomes by rationally designed deletions to create simplified cells with predictable behavior that act as a platform to build in various genetic systems for specific purposes. We report a novel Bacillus subtilis strain, MBG874, depleted of 874 kb (20%) of the genomic sequence. When compared with wild-type cells, the regulatory network of gene expression of the mutant strain is reorganized after entry into the transition state due to the synergistic effect of multiple deletions, and productivity of extracellular cellulase and protease from transformed plasmids harboring the corresponding genes is remarkably enhanced. To our knowledge, this is the first report demonstrating that genome reduction actually contributes to the creation of bacterial cells with a practical application in industry. Further systematic analysis of changes in the transcriptional regulatory network of MGB874 cells in relation to protein productivity should facilitate the generation of improved B. subtilis cells as hosts of industrial protein production.
authors.affiliation: Biological Science Laboratories, Kao Corporation, 2606 Akabane, Ichikai, Haga, Tochigi 321-3497, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Morimoto
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kadoya
authors.forename: Keiji
authors.initials: K
authors.lastname: Endo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Tohata
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Sawada
authors.forename: Shengao
authors.initials: S
authors.lastname: Liu
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Ozawa
authors.forename: Takeko
authors.initials: T
authors.lastname: Kodama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kakeshita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kageyama
authors.forename: Kenji
authors.initials: K
authors.lastname: Manabe
authors.forename: Shigehiko
authors.initials: S
authors.lastname: Kanaya
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Ara
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ozaki
authors.forename: Naotake
authors.initials: N
authors.lastname: Ogasawara
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D044602:Cellulases / Q000235:genetics / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D007218:Industrial Microbiology / Q000379:methods*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D013171:Spores, Bacterial
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D044602:Cellulases; D010450:Endopeptidases; C087822:alkaline protease