Design of novel branched chain amino acids with metabolic control function for clinical improvement of lifestyle diseases.

• Project/Area Number: 22658027
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Applied microbiology
• Research Institution: Kyoto University
• Principal Investigator: OGAWA Jun 京都大学, 大学院・農学研究科, 教授 (70281102)
• Co-Investigator(Kenkyū-buntansha): HIBI Makoto 京都大学, 農学研究科, 助教 (30432347) ; HAGISHITA Tairo 京都大学, 農学研究科, 准教授 (20432346)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,650,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2010: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 分岐鎖アミノ酸 / 4-ヒドロキシイソロイシン / 肥満 / 糖尿病 / ジオキシゲナーゼ / アルドラーゼ / トランスアミナーゼ / 水酸化アミノ酸

Research Abstract

In this study, we attempted to construct novel synthetic procedures for the physiologically active amino acid production, such as hydroxylated branched chain amino acid derivatives, using enzymes involved in newly found microbial branched chain amino acid metabolisms. As the results, streroselectve fine syntheses, such as hydroxylated aliphatic amino acids by dioxygenases, hydroxylated amino acids by aldolases, and 4-hydroxyisoleucine stereoisomers by oxidoreductases were established.

Research Products

• [Journal Article] Characterization of Bacillus thuringiensis L-isoleucine dioxygenase toward the production of useful amino acids (2011)
  • Author(s): Hibi, M., T.Kawashima, T.Kodera, S.V.Smirnov, P.M.Sokolov, M.Sugiyama, S.Shimizu, K.Yokozeki, J.Ogawa
  • Journal Title: Appl.Environ.Microbiol. Volume: 77 Issue: 19 Pages: 6926-6930
  • DOI: 10.1128/aem.05035-11
  • Peer Reviewed
• [Journal Article] アミノ酸水酸化触媒としてのα-ケトグルタル酸依存性ジオキシゲナーゼ (2011)
  • Author(s): 日比慎、小川順
  • Journal Title: バイオサイエンスとインダストリー Volume: Vol.69 Pages: 384-38
  • NAID: 10029466411
• [Journal Article] 代謝的視点からの機能探索に基づく産業プロセス用酵素開発 (2011)
  • Author(s): 小川順、櫻谷英治、岸野重信、日比慎(4)、堀之内伸行、横関健三、清水昌
  • Journal Title: BIOINDUSTRY Volume: Vol.28 Pages: 7-1
• [Journal Article] A novel l-isoleucine metabolism in Bacillus thuringiensis generating(2S, 3R, 4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid (2011)
  • Author(s): Ogawa, J., T. Kodera, S. V. Smirnov, M. Hibi N. N. Samsonova, R. Koyama, H. Yamanaka, J. Mano, T. Kawashima, K. Yokozeki, S. Shimizu
  • Journal Title: Applied Microbiology and Biotechnology Volume: Vol.89 Issue: 6 Pages: 1929-1938
  • DOI: 10.1007/s00253-010-2983-7
  • Peer Reviewed
• [Journal Article] Metabolic engineering of Escherichia call to produce(2S, 3R, 4S)-4-hydroxyi soleucine (2011)
  • Author(s): Smirnov, S. V., T. Kodera, N. N. Samsonova, V. A. Kotlyarov a, N. Y. Rushkevich, A. D. Kivero, P. M. Sokolov, M. Hibi, J. Ogawa, S. Shimizu.
  • Journal Title: Applied Microbiology and Biotechnology Volume: Vol.88 Issue: 3 Pages: 719-726
  • DOI: 10.1007/s00253-010-2772-3
  • Peer Reviewed
• [Journal Article] A novel l-isoleucine metabolism in Bacillus thuringiensis generating (2S,3R,4S)-4-hydroxyisoleucine, a potential insulinotropic and anti-obesity amino acid. (2011)
  • Author(s): J.Ogawa, et.al.
  • Journal Title: Appl Microbiol.Biotechnol. Volume: 89(6)(in press) Pages: 1929-1938
  • Peer Reviewed
• [Journal Article] Metabolic engineering of Escherichia coli to produce (2S,3R,4S)-4-hydroxyisoleucine (2010)
  • Author(s): S.V.Smirnov, J.Ogawa, et.al.
  • Journal Title: Appl.Microbiol.Biotechnol. Volume: 88(3) Pages: 719-726
  • Peer Reviewed
• [Presentation] Bacillus thuringiensis 2e2株由来Fe(II)/α-ケトグルタル酸依存性ジオキシゲナーゼによる光学活性スルフォキシド生産 (2012)
  • Author(s): 日比慎、清水昌、横関健三、小川順
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都(京都女子大学)
  • Year and Date: 2012-03-25
• [Presentation] アミノ基修飾酵素と水酸化酵素を共役させたβ-ヒドロキシアミノ酸生産系の開発 (2012)
  • Author(s): 日比慎、笠原拓也、河嶋隆志、横関健三、清水昌、小川順
  • Organizer: 日本農芸化学会2012年度大会
  • Place of Presentation: 京都(京都女子大学)
  • Year and Date: 2012-03-25
• [Presentation] Novel dioxygenases for hydroxy amino acid production (2011)
  • Author(s): Hibi M., Shimizu S., Yokozeki K., Ogawa J.
  • Organizer: Biotrans 2011
  • Place of Presentation: Sicilia, Italia
  • Year and Date: 2011-10-04
• [Presentation] α-ケトグルタル酸依存性ジオキシゲナーゼを利用した有用アミノ酸の立体選択的生産 (2011)
  • Author(s): 日比慎、河嶋隆志、清水昌、横関健三、小川順
  • Organizer: 第63回日本生物工学会大会
  • Place of Presentation: 東京(東京大学)
  • Year and Date: 2011-09-26
• [Presentation] α-Ketoglutarate-dependent dioxyge-nase : Biocatalyst for useful amino acid production (2011)
  • Author(s): Hibi M., Shimizu S., Yokozeki K., Ogawa J
  • Organizer: The 16th Japanese-German Workshop on Enzyme Technology
  • Place of Presentation: 富山(富山国際会議場)
  • Year and Date: 2011-09-14
• [Presentation] Development of Microbial Multi-component Enzyme Systems (2011)
  • Author(s): J.Ogawa, et.al.
  • Organizer: IUMS 2011 XIII International Congress of Bacteriology and Applied Microbiology
  • Place of Presentation: 札幌コンベンションセンター(招待講演)
  • Year and Date: 2011-09-07
• [Presentation] Bacillus thuringiensis 2e2株由来L-isoleucine dioxygenaseによる有用アミノ酸の立体選択的合成 (2011)
  • Author(s): 日比慎、河嶋隆志、清水昌、横関健三、小川順
  • Organizer: 日本農芸化学会2011年度大会
  • Place of Presentation: 京都(京都女子大学)
  • Year and Date: 2011-03-26
• [Presentation] バイオベースケミカルインダストリーを創出する有用微生物機能の設計・探索・開発 (2010)
  • Author(s): 小川順
  • Organizer: JBA新資源生物変換研究会シンポジウム「2020年のバイオインダストリー」
  • Place of Presentation: 東京大学(東京)
  • Year and Date: 2010-10-01
• [Presentation] A novel aliphatic amino acid metabolism in bacteria generating apotential insulinotropic and antiobesity amino acid (2010)
  • Author(s): J.Ogawa, et.al.
  • Organizer: 101st AOCS Annual Meeting & Expo
  • Place of Presentation: Phoenix(USA)
  • Year and Date: 2010-05-17