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Science 19 September 1997:
Vol. 277. no. 5333, pp. 1815 - 1820
DOI: 10.1126/science.277.5333.1815
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Reports

Structural Basis for Cyclic Terpene Biosynthesis by Tobacco 5-Epi-Aristolochene Synthase

Courtney M. Starks, Kyoungwhan Back, Joseph Chappell, Joseph P. Noel *

Terpene cyclases catalyze the synthesis of cyclic terpenes with 10-, 15-, and 20-carbon acyclic isoprenoid diphosphates as substrates. Plants have been a source of these natural products by providing a homologous set of terpene synthases. The crystal structures of 5-epi-aristolochene synthase, a sesquiterpene cyclase from tobacco, alone and complexed separately with two farnesyl diphosphate analogs were analyzed. These structures reveal an unexpected enzymatic mechanism for the synthesis of the bicyclic product, 5-epi-aristolochene, and provide a basis for understanding the stereochemical selectivity displayed by other cyclases in the biosynthesis of pharmacologically important cyclic terpenes. As such, these structures provide templates for the engineering of novel terpene cyclases.

C. M. Starks and J. P. Noel, Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA, and Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0301, USA.
K. Back and J. Chappell, Plant Physiology, Biochemistry, and Molecular Biology Program, University of Kentucky, Lexington, KY 40546-0091, USA.
*   To whom correspondence should be addressed. E-mail: noel{at}sbl.salk.edu

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From the Cover: Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade.
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   Abstract »    Full Text »    PDF »


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