InterPro domain: IPR044814

This entry includes a diverse group of monomeric plant terpene cyclases (Tspa-Tspf) that convert the acyclic isoprenoid diphosphates, geranyl diphosphate (GPP), farnesyl diphosphate (FPP), or geranylgeranyl diphosphate (GGPP) into cyclic monoterpenes, diterpenes, or sesquiterpenes, respectively; a few form acyclic species. Terpenoid cyclases are soluble enzymes localized to the cytosol (sesquiterpene synthases) or plastids (mono- and diterpene synthases). All monoterpene and diterpene synthases have restrict substrate specificity, however, some sesquiterpene synthases can accept both FPP and GPP [ 1 , 2 , 3 ].

The catalytic site consists of a large central cavity formed by mostly antiparallel alpha helices with two aspartate-rich regions located on opposite walls. These residues mediate binding of prenyl diphosphates, via bridging Mg2+ ions (K+ preferred by gymnosperm cyclases), inducing conformational changes such that an N-terminal region forms a cap over the catalytic core. Loss of diphosphate from the enzyme-bound substrate (GPP, FPP, or GGPP) results in an allylic carbocation that electrophilically attacks a double bond further down the terpene chain to effect the first ring closure. Unlike monoterpene, sesquiterpene, and macrocyclic diterpenes synthases, which undergo substrate ionization by diphosphate ester scission, Tpsc-like diterpene synthases catalyse cyclization reactions by an initial protonation step producing a copalyl diphosphate intermediate. These enzymes lack the aspartate-rich sequences mentioned above [ 4 , 5 , 6 ]. Most diterpene synthases have an N-terminal, internal element (approx 210 aa) whose function is unknown.

1. Structure, mechanism and function of prenyltransferases. Eur. J. Biochem. 269, 3339-54
2. Molecular scaffolds for chemical wizardry: learning nature's rules for terpene cyclases. Proc. Natl. Acad. Sci. U.S.A. 98, 13479-81
3. The biosynthesis of C5-C25 terpenoid compounds. Nat Prod Rep 19, 181-222
4. Plant terpenoid synthases: molecular biology and phylogenetic analysis. Proc. Natl. Acad. Sci. U.S.A. 95, 4126-33
5. Structural basis for cyclic terpene biosynthesis by tobacco 5-epi-aristolochene synthase. Science 277, 1815-20
6. Bornyl diphosphate synthase: structure and strategy for carbocation manipulation by a terpenoid cyclase. Proc. Natl. Acad. Sci. U.S.A. 99, 15375-80