Discovery of novel enantioselective imine reductases and efficient enzyme synthesis of optically active amines

• Project/Area Number: 23560941
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biofunction/Bioprocess
• Research Institution: Gifu University
• Principal Investigator: MITSUKURA Koichi 岐阜大学, 工学部, 准教授 (70324283)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Toyokazu 岐阜大学, 工学部, 教授 (90220657)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: Chiral amine / Enantioselectivity / Enzymatic synthesis / Imine reductase / イミン還元酵素 / エナンチオ選択的 / キラルアミン / 基質特異性 / 組換え菌作製 / 不斉還元 / 光学活性アミン / イミン不斉還元

Research Abstract

Chiral amines are useful compounds for the synthesis of pharmaceuticals. In an efficient chemical synthesis of optically active amine, asymmetric reduction of imine has been well studied. However, enzymatic reduction of synthetic imine have not been reported yet. We therefore surveyed imine reductase from soil samples , and first found R-and S-imine reductases. After purification and characterization of the enzymes, gene analysis and preparation of recombinant cells were performed. We efficiently synthesized optically active amines with high optical purity using their imine reductases.

Research Products

• [Journal Article] A NADPH-dependent (S)-imine reductase (SIR) from Streptomyces sp. GF3546 for asymmetric synthesis of optically active amines : purification,characterization,gene cloning,and expression (2013)
  • Author(s): 満倉浩一, 倉本達也, 吉田豊和, 木本訓弘, 山本浩明, 長津透
  • Journal Title: Appl. Microbiol. Biotechnol. Volume: 97 Pages: 8079-8086
  • Peer Reviewed
• [Journal Article] A NADPH-dependent (S)-imine reductase (SIR) from Streptomyces sp. GF3546 for asymmetric synthesis of optically active amines: purification, characterization, gene cloning, and expression. (2013)
  • Author(s): K. Mitsukura, T. Kuramoto, T. Yoshida, N. Kimoto, H. Yamamoto and T. NagasawaK. Mitsukura, M. Suzuki, S. Shinoda, T. Kuramoto, T. Yoshida and T. Nagasawa
  • Journal Title: Appl. Microbiol. Biotechnol. Volume: 97 Issue: 18 Pages: 8079-8086
  • DOI: 10.1007/s00253-012-4629-4
  • Peer Reviewed
• [Journal Article] 化学と生物新規エナンチオ選択的イミン還元酵素の探索と発見 (2012)
  • Author(s): 満倉浩一, 長津透
  • Volume: 65
  • Pages: 158-160
• [Journal Article] 新規エナンチオ選択的イミン還元酵素の探索と発見 (2012)
  • Author(s): 滿倉浩一、長澤 透
  • Journal Title: 化学と生物 Volume: 50(3) Pages: 158-160
• [Journal Article] Purification and characterization of a novel (R)-Imine reductase from Streptomyces sp. GF3587 (2011)
  • Author(s): 満倉浩一, 鈴木麻衣, 篠田祥, 倉本達也, 吉田豊和, 長津透
  • Journal Title: Biosci. Biotechnol. Biochem. Volume: 75 Pages: 1778-1782
  • NAID: 10029757388
  • Peer Reviewed
• [Journal Article] 新規エナンチオ選択的イミン還元酵素の発見とその特徴解析 (2011)
  • Author(s): 満倉浩一, 長津透
  • Journal Title: 酵素工学ニュース Volume: 50 Pages: 23-25
• [Journal Article] (R)-イミン還元酵素の精製と特徴解析 (2011)
  • Author(s): 滿倉浩一、鈴木麻衣、篠田 祥、倉本達也、吉田豊和、長澤 透
  • Journal Title: BIOSCIENCE, BIOTECHNOLOGY AND BIOCHEMISTRY Volume: 75(9) Pages: 1778-1782
  • Peer Reviewed
• [Presentation] Application of enantioselective imine reductases for the synthesis of optically active amines (2013)
  • Author(s): 満倉浩一, 吉田豊和, 長津透
  • Organizer: Enzyme Engineering XXII
  • Place of Presentation: 富山
  • Year and Date: 2013-09-24
• [Presentation] Asymmetric synthesis of optically active amines from imines using enantioselective imine reductases (2013)
  • Author(s): 満倉浩一, 吉田豊和, 長津透
  • Organizer: Biotrans 2013
  • Place of Presentation: マンチェスター、イギリス
  • Year and Date: 2013-07-22
• [Presentation] Asymmetric Synthesis of Optically Active Amines from Imines using Enantioselective Imine Reductases (2013)
  • Author(s): K. Mitsukura
  • Organizer: Biotrans2013
  • Place of Presentation: Manchester, UK
• [Presentation] エナンチオ選択的イミン還元酵素を利用した光学活性アミン合成 (2012)
  • Author(s): 満倉浩一, 吉田豊和, 長津透
  • Organizer: 生体触媒化学シンポジウム
  • Place of Presentation: 富山
  • Year and Date: 2012-11-30
• [Presentation] (S)-イミン還元酵素による光学活性アミン合成 (2012)
  • Author(s): 満倉浩一, 福岡達也, 倉本達也, 吉田豊和, 長津透
  • Organizer: 日本生物工学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-10-24
• [Presentation] (S)-イミン還元酵素による光学活性アミン合成 (2012)
  • Author(s): 満倉浩一，○福岡達也，倉本達也，吉田豊和，長澤 透
  • Organizer: 日本生物工学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Occurrence and characterization of a novel imine reductase (2011)
  • Author(s): 満倉浩一, 吉田豊和, 長津透
  • Organizer: Biotrans 2011
  • Place of Presentation: シチリア島、イタリア
  • Year and Date: 2011-10-03
• [Presentation] Occurrence and Characterization of Novel Imine Reductase (2011)
  • Author(s): ○満倉浩一，吉田豊和，長澤 透
  • Organizer: BIOTRANS2011
  • Place of Presentation: イタリア、シチリア島