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New insights into short-chain prenyltransferases: structural features, evolutionary history and potential for selective inhibition

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Abstract

Isoprenoids form an extensive group of natural products involved in a number of important biological processes. Their biosynthesis proceeds through sequential 1′-4 condensations of isopentenyl diphosphate (C5) with an allylic acceptor, the first of which is dimethylallyl diphosphate (C5). The reactions leading to the production of geranyl diphosphate (C10), farnesyl diphosphate (C15) and geranylgeranyl diphosphate (C20), which are the precursors of mono-, sesqui- and diterpenes, respectively, are catalyzed by a group of highly conserved enzymes known as short-chain isoprenyl diphosphate synthases, or prenyltransferases. In recent years, the sequences of many new prenyltransferases have become available, including those of several plant and animal geranyl diphosphate synthases, revealing novel mechanisms of product chain-length selectivity and an intricate evolutionary path from a putative common ancestor. Finally, there is considerable interest in designing inhibitors specific to short-chain prenyltransferases, for the purpose of developing new drugs or pesticides that target the isoprenoid biosynthetic pathway.

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Acknowledgments

This work was supported by a PhD scholarship to S.V., awarded by the “Fonds pour la formation à la Recherche dans l’Industrie et l’Agriculture” (Belgium) and an NSERC Discovery Grant to M.C.

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  1. Department of Functional and Evolutionary Entomology, Gembloux Agricultural University, Passage des Déportés 2, 5030, Gembloux, Belgium

    Sophie Vandermoten & Éric Haubruge

  2. Laurentian Forestry Centre, Canadian Forest Service, Natural Resources Canada, 1055 du PEPS, P.O. Box 10380, Stn. Ste-Foy, Quebec, QC, G1V4C7, Canada

    Michel Cusson

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  1. Sophie Vandermoten
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Correspondence to Sophie Vandermoten.

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Vandermoten, S., Haubruge, É. & Cusson, M. New insights into short-chain prenyltransferases: structural features, evolutionary history and potential for selective inhibition. Cell. Mol. Life Sci. 66, 3685–3695 (2009). https://doi.org/10.1007/s00018-009-0100-9

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