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A potential energy surface bifurcation in terpene biosynthesis

Nature Chemistry volume 1, pages 384–389 (2009)Cite this article

Abstract

Terpenes comprise a class of natural products that includes molecules with thousands of distinct structurally and stereochemically complex molecular architectures. The core hydrocarbon frameworks of these molecules are constructed via carbocation rearrangements promoted by terpene synthase (cyclase) enzymes. Although many mechanistic details for such reactions have been uncovered, the factors that control which carbocation intermediates and transition-state structures form are not well understood. Here we show that rearrangement pathways that pass through particular transition-state structures can bifurcate after the transition state. The resulting pathways lead to terpenes with distinctly different skeletons from each other. Although these types of bifurcating pathways have been described previously for some small molecules, the possibility that they may have an important role in the production of complex molecules in nature has, to our knowledge, not previously been considered.

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Figure 1: The putative intramolecular proton-transfer step in the reaction of copalyl diphosphate, catalysed by abietadiene synthase, to give abietadiene.
Figure 2: Computed energies for structures involved in the rearrangement of 1a and 1b.
Figure 3: Dyotropic rearrangement that interconverts 4b and 3b/c.
Figure 4: Computed reaction pathways through TSre (1b–3b/4b) and TS (3b–4b).

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Acknowledgements

We gratefully acknowledge the University of California, Davis, and the National Science Foundation's CAREER and Partnership for Advanced Computational Infrastructure programmes for their support. We are also grateful to M. W. Lodewyk, M. R. Siebert and S. C. Wang (University of California, Davis) for helpful comments.

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Authors and Affiliations

  1. Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California, 95616, USA

    Young J. Hong & Dean J. Tantillo

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  1. Young J. Hong
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Contributions

D.J.T. and Y.J.H. conceived and designed the experiments, analysed the data and co-wrote the paper. Y.J.H. performed the experiments.

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Correspondence to Dean J. Tantillo.

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Hong, Y., Tantillo, D. A potential energy surface bifurcation in terpene biosynthesis. Nature Chem 1, 384–389 (2009). https://doi.org/10.1038/nchem.287

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