Structural basis for cyclic terpene biosynthesis by tobacco 5-epi-aristolochene synthase.
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.
Starks
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CM
Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
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Chappell
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D019883:Alkyl and Aryl Transferases; D001665:Binding Sites; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D018360:Crystallography, X-Ray; D003500:Cyclization; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D010947:Plants, Toxic; D011106:Polyisoprenyl Phosphates / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011522:Protons; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D014026:Nicotiana / Q000201:enzymology*; D014166:Transferases / Q000737:chemistry* / Q000378:metabolism
C108196:5-epi-aristolochene; D011106:Polyisoprenyl Phosphates; D011522:Protons; D012717:Sesquiterpenes; C004808:farnesyl pyrophosphate; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C078217:5-epi-aristolochene synthase; C092952:vetispiradiene synthase; D008274:Magnesium