title: Enhanced dipicolinic acid production during the stationary phase in Bacillus subtilis by blocking acetoin synthesis.
abstract: Bacterial bio-production during the stationary phase is expected to lead to a high target yield because the cells do not consume the substrate for growth. Bacillus subtilis is widely used for bio-production, but little is known about the metabolism during the stationary phase. In this study, we focused on the dipicolinic acid (DPA) production by B. subtilis and investigated the metabolism. We found that DPA production competes with acetoin synthesis and that acetoin synthesis genes (alsSD) deletion increases DPA productivity by 1.4-fold. The mutant showed interesting features where the glucose uptake was inhibited, whereas the cell density increased by approximately 50%, resulting in similar volumetric glucose consumption to that of the parental strain. The metabolic profiles revealed accumulation of pyruvate, acetyl-CoA, and the TCA cycle intermediates in the alsSD mutant. Our results indicate that alsSD-deleted B. subtilis has potential as an effective host for stationary-phase production of compounds synthesized from these intermediates.
authors.affiliation: a Department of Bioinformatic Engineering , Graduate School of Information Science and Technology, Osaka University , Suita , Japan.|b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Toya
authors.affiliation: a Department of Bioinformatic Engineering , Graduate School of Information Science and Technology, Osaka University , Suita , Japan.|b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|c Department of Bioengineering , Tokyo Institute of Technology , Yokohama , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirasawa
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|d Graduate School of Biological Science , Nara Institute of Science and Technology , Ikoma , Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|d Graduate School of Biological Science , Nara Institute of Science and Technology , Ikoma , Japan.
authors.forename: Onuma
authors.initials: O
authors.lastname: Chumsakul
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|e Biological Science Laboratories , Kao Corporation , Haga , Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Morimoto
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|e Biological Science Laboratories , Kao Corporation , Haga , Japan.
authors.forename: Shenghao
authors.initials: S
authors.lastname: Liu
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|e Biological Science Laboratories , Kao Corporation , Haga , Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|e Biological Science Laboratories , Kao Corporation , Haga , Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kageyama
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|e Biological Science Laboratories , Kao Corporation , Haga , Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Ozaki
authors.affiliation: b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.|d Graduate School of Biological Science , Nara Institute of Science and Technology , Ikoma , Japan.
authors.forename: Naotake
authors.initials: N
authors.lastname: Ogasawara
authors.affiliation: a Department of Bioinformatic Engineering , Graduate School of Information Science and Technology, Osaka University , Suita , Japan.|b Advanced Low Carbon Technology Research and Development Program , Japan Science and Technology Agency (JST, ALCA) , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000093:Acetoin / Q000378:metabolism*; D001412:Bacillus subtilis / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics; D001709:Biotechnology; D046508:Culture Techniques; D005947:Glucose / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D010848:Picolinic Acids / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010848:Picolinic Acids; D000093:Acetoin; D005947:Glucose; C004860:dipicolinic acid
keywords: Bacillus subtilis; alsSD; dipicolinic acid; stationary phase metabolism