A bacterial platform for fermentative production of plant alkaloids

Akira Nakagawa, Hiromichi Minami (), Ju-Sung Kim, Takashi Koyanagi, Takane Katayama, Fumihiko Sato and Hidehiko Kumagai
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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
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

Nature Communications, 2011, vol. 2, issue 1, 1-9

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1327

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