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Acetylation serves as a protective group in noscapine biosynthesis in opium poppy

Nature Chemical Biology volume 11, pages 104–106 (2015)Cite this article

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Abstract

We have characterized four sequential enzymes that transform 1-hydroxy-N-methylcanadine to narcotoline hemiacetal, completing our elucidation of noscapine biosynthesis in opium poppy. Two cytochromes P450 catalyze hydroxylations at C13 and C8 on the protoberberine scaffold, the latter step inducing ring opening and the formation of an aldehyde moiety. Acetylation at C13 before C8 hydroxylation introduces a protective group subsequently hydrolyzed by a carboxylesterase, which triggers rearrangement to a cyclic hemiacetal.

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Figure 1: Biosynthesis of noscapine from (S)-N-methylcanadine in opium poppy.
Figure 2: Enzymatic functions of CYP82X2, AT1, CYP82X1 and CXE1.
Figure 3: VIGS supports the involvement of CYP82X1, CYP82X2, AT1 and CXE1 in the biosynthesis of noscapine in opium poppy.

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Acknowledgements

We thank D. Burns and J. Hagel for the NMR and LTQ-Orbitrap analyses, respectively. T.-T.T.D. is the recipient of the Alberta Innovates Technology Futures and University of Calgary Eyes High graduate scholarships. Funding was provided through grants from Genome Canada, Genome Alberta, the Government of Alberta (URSI-10-004-SEG), the Canada Foundation for Innovation (CFI-21695) and the Natural Sciences and Engineering Research Council of Canada (RGPIN/183573-2009) to P.J.F.

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  1. Thu-Thuy T Dang and Xue Chen: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Sciences, University of Calgary, Calgary, Alberta, Canada

    Thu-Thuy T Dang, Xue Chen & Peter J Facchini

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  1. Thu-Thuy T Dang
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  2. Xue Chen
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Contributions

T.-T.T.D. and X.C. contributed equally to all experiments. P.J.F. was responsible for experimental design. All authors contributed to the preparation of the manuscript.

Corresponding author

Correspondence to Peter J Facchini.

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Competing interests

P.J.F., T.-T.T.D. and X.C. have filed a patent application (Patent Cooperation Treaty Application PCT/CA2014/050782) covering compositions and methods related to the manufacture of noscapine and synthesis intermediates thereof.

Supplementary information

Supplementary Text and Figures

Supplementary Results, Supplementary Figures 1–18 and Supplementary Tables 1–7. (PDF 20145 kb)

Supplementary Data Set 1

1H, 13C, COSY, HSQC, HMBC, and NOESY NMR spectral data for (13S,14R)-1,13-dihydroxy-N-methylcanadine (m/z 386) and 1H, COSY, HSQC and HMBC NMR spectral data for (13S,14R)-1-hydroxy-13-O-acetyl-N-methylcanadine (m/z 428). (PDF 898 kb)

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Dang, TT., Chen, X. & Facchini, P. Acetylation serves as a protective group in noscapine biosynthesis in opium poppy. Nat Chem Biol 11, 104–106 (2015). https://doi.org/10.1038/nchembio.1717

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