Issue 2, 2020

Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route

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

Supplementary files

Article information

Article type
Edge Article
Submitted
30 7月 2019
Accepted
17 11月 2019
First published
18 11月 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2020,11, 364-371

Biosynthesis of plant tetrahydroisoquinoline alkaloids through an imine reductase route

L. Yang, J. Zhu, C. Sun, Z. Deng and X. Qu, Chem. Sci., 2020, 11, 364 DOI: 10.1039/C9SC03773J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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