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Structural determinants of reductive terpene cyclization in iridoid biosynthesis

Nature Chemical Biology volume 12, pages 6–8 (2016)Cite this article

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Abstract

The carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. Here we report the crystal structure of the recently discovered iridoid cyclase (from Catharanthus roseus) bound to a mechanism-inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. Key features that distinguish iridoid synthase from its close homolog progesterone 5β-reductase are highlighted.

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Figure 1: Mechanism of iridoid synthase (ISY).
Figure 2: Structure of ISY (Catharanthus roseus, CrISY).
Figure 3: Open and closed forms of loop Gly150–Val158 in CrISY.

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  • 11 May 2018

    In the version of this article originally published, the grant number given for funding by the European Research Council was R20359 instead of 311363. The error has been corrected in the HTML and PDF versions of the paper.

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Acknowledgements

Funds were made available by the European Research Council (ERC 311363) and a BBSRC Institute Strategic Programme grant (MET; BB/J004561/1) to S.E.O'C., and an SNF Early Postdoc Mobility Fellowship to H.K. The Diamond Light Source provided access to beamlines I03, I04 and I04-1 (proposal MX9475).

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Author notes

  1. Hajo Kries and Lorenzo Caputi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biological Chemistry, The John Innes Centre, Norwich Research Park, Norwich, UK

    Hajo Kries, Lorenzo Caputi, Clare E M Stevenson, Mohammed O Kamileen, Nathaniel H Sherden, David M Lawson & Sarah E O'Connor

  2. Department of Plant and Environmental Sciences, University of Copenhagen, Copenhagen Plant Science Centre & Section for Plant Biochemistry, Copenhagen, Denmark

    Fernando Geu-Flores

Authors
  1. Hajo Kries
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  2. Lorenzo Caputi
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  6. Fernando Geu-Flores
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  7. David M Lawson
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  8. Sarah E O'Connor
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Contributions

L.C., H. K., N.H.S., F.G.-F., and S.E.O'C. designed the project; L.C., H.K., M.O.K., and F.G.-F. performed molecular cloning/enzyme assays; C.E.M.S. assisted with crystallization and X-ray data acquisition; H.K., F.G.-F., and N.H.S. performed chemical synthesis; H.K., L.C., and D.M.L. refined structures; S.E.O'C. supervised the work; H.K. and S.E.O'C. wrote the manuscript.

Corresponding author

Correspondence to Sarah E O'Connor.

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The authors declare no competing financial interests.

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Supplementary Tables 1–4 and Supplementary Figures 1–14. (PDF 6518 kb)

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Kries, H., Caputi, L., Stevenson, C. et al. Structural determinants of reductive terpene cyclization in iridoid biosynthesis. Nat Chem Biol 12, 6–8 (2016). https://doi.org/10.1038/nchembio.1955

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