Laboratory-scale production of (<i>S</i>)-reticuline, an important intermediate of benzylisoquinoline alkaloids, using a bacterial-based method

  • Eitaro Matsumura
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan
  • Akira Nakagawa
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan
  • Yusuke Tomabechi
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan
  • Takashi Koyanagi
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan
  • Hidehiko Kumagai
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan
  • Kenji Yamamoto
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan
  • Takane Katayama
    Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
  • Fumihiko Sato
    Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University, Kyoto, Japan
  • Hiromichi Minami
    Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi, Japan

説明

<jats:title>Abstract</jats:title> <jats:p>Benzylisoquinoline alkaloids (BIAs) are a group of plant secondary metabolites that have been identified as targets for drug discovery because of their diverse pharmaceutical activities. Well-known BIAs are relatively abundant in plants and have therefore been extensively studied. However, although unknown BIAs are also thought to have valuable activities, they are difficult to obtain because the raw materials are present at low abundance in nature. We have previously reported the fermentative production of an important intermediate (S)-reticuline from dopamine using Escherichia coli. However, the yield is typically limited. Here, we improved production efficiency by combining in vivo tetrahydropapaveroline production in E. coli with in vitro enzymatic synthesis of (S)-reticuline. Finally, 593 mg of pure (S)-reticuline was obtained from 1 L of the reaction mixture. Because this bacterial-based method is simple, it could be widely used for production of (S)-reticuline and related BIAs, thereby facilitating studies of BIAs for drug discovery.</jats:p>

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