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A bacterial platform for fermentative production of plant alkaloids

Author

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  • Akira Nakagawa

    (Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-machi)

  • Hiromichi Minami

    (Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-machi)

  • Ju-Sung Kim

    (Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-machi
    Present address: College of Applied Life Sciences, Jeju National University, Jeju 690-756, South Korea.)

  • Takashi Koyanagi

    (Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-machi)

  • Takane Katayama

    (Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-machi)

  • Fumihiko Sato

    (Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku)

  • Hidehiko Kumagai

    (Research Institute for Bioresources and Biotechnology, Ishikawa Prefectural University, Nonoichi-machi)

Abstract

The secondary metabolites of higher plants include diverse chemicals, such as alkaloids, isoprenoids and phenolic compounds (phenylpropanoids and flavonoids). Although these compounds are widely used in human health and nutrition, at present they are mainly obtained by extraction from plants and extraction yields are low because most of these metabolites accumulate at low levels in plant cells. Recent advances in synthetic biology and metabolic engineering have enabled tailored production of plant secondary metabolites in microorganisms, but these methods often require the addition of expensive substrates. Here we develop an Escherichia coli fermentation system that yields plant alkaloids from simple carbon sources, using selected enzymes to construct a tailor-made biosynthetic pathway. In this system, engineered cells cultured in growth medium without additional substrates produce the plant benzylisoquinoline alkaloid, (S)-reticuline (yield, 46.0 mg l−1 culture medium). The fermentation platform described here offers opportunities for low-cost production of many diverse alkaloids.

Suggested Citation

  • Akira Nakagawa & Hiromichi Minami & Ju-Sung Kim & Takashi Koyanagi & Takane Katayama & Fumihiko Sato & Hidehiko Kumagai, 2011. "A bacterial platform for fermentative production of plant alkaloids," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1327
    DOI: 10.1038/ncomms1327
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    Cited by:

    1. Yue Gao & Fei Li & Zhengshan Luo & Zhiwei Deng & Yan Zhang & Zhenbo Yuan & Changmei Liu & Yijian Rao, 2024. "Modular assembly of an artificially concise biocatalytic cascade for the manufacture of phenethylisoquinoline alkaloids," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    2. Christopher J. Vavricka & Shunsuke Takahashi & Naoki Watanabe & Musashi Takenaka & Mami Matsuda & Takanobu Yoshida & Ryo Suzuki & Hiromasa Kiyota & Jianyong Li & Hiromichi Minami & Jun Ishii & Kenji T, 2022. "Machine learning discovery of missing links that mediate alternative branches to plant alkaloids," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Yu Wang & Fabiana Subrizi & Eve M. Carter & Tom D. Sheppard & John M. Ward & Helen C. Hailes, 2022. "Enzymatic synthesis of benzylisoquinoline alkaloids using a parallel cascade strategy and tyrosinase variants," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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