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Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route

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Abstract

Herein, we report a biocatalytic approach to synthesize plant tetrahydroisoquinoline alkaloids (THIQAs) from dihydroisoquinoline (DHIQ) precursors using imine reductases and N-methyltransferase (NMT). The imine reductase IR45 was engineered to significantly expand its substrate specificity, enabling efficient and stereoselective conversion of 1-phenyl and 1-benzyl 6,7-dimethoxy-DHIQs into the corresponding (S)-tetrahydroisoquinolines (S-THIQs). Coclaurine N-methyltransferase (CNMT) was able to further efficiently convert these (S)-THIQ intermediates into (S)-THIQAs. By assembling IRED, CNMT, and glucose dehydrogenase (GDH) in one reaction, we effectively constituted two artificial biosynthetic pathways in Escherichia coli and successfully applied them to the production of five (S)-THIQAs. This highly efficient (100% yield from DHIQs) and easily tailorable (adding other genes) biosynthetic approach will be useful for producing a variety of plant THIQAs.

Graphical abstract: Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route

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Publication details

The article was received on 30 Jul 2019, accepted on 17 Nov 2019 and first published on 18 Nov 2019


Article type: Edge Article
DOI: 10.1039/C9SC03773J
Chem. Sci., 2020, Advance Article
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route

    L. Yang, J. Zhu, C. Sun, Z. Deng and X. Qu, Chem. Sci., 2020, Advance Article , DOI: 10.1039/C9SC03773J

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