title: Laboratory-scale production of (S)-reticuline, an important intermediate of benzylisoquinoline alkaloids, using a bacterial-based method.
abstract: 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.
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Eitaro
authors.initials: E
authors.lastname: Matsumura
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawa
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tomabechi
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Kumagai
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: b Division of Integrated Life Science, Graduate School of Biostudies , Kyoto University , Kyoto , Japan.
authors.forename: Takane
authors.initials: T
authors.lastname: Katayama
authors.affiliation: b Division of Integrated Life Science, Graduate School of Biostudies , Kyoto University , Kyoto , Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.affiliation: a Research Institute for Bioresources and Biotechnology , Ishikawa Prefectural University , Nonoichi , Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Minami
mesh_terms: D044182:Benzylisoquinolines / Q000737:chemistry* / Q000378:metabolism; D019149:Bioreactors / Q000382:microbiology*; D004298:Dopamine / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism*; D007753:Laboratories; D013765:Tetrahydropapaveroline / Q000378:metabolism
chemical_list: D044182:Benzylisoquinolines; D013765:Tetrahydropapaveroline; D004298:Dopamine; C003298:reticuline
keywords: bacterial production; benzylisoquinoline alkaloid; drug discovery; reticuline; synthetic biology