InterPro domain: IPR034686

Characterized enzymes in the terpene cyclase like 2 family include sesquiterpene cyclases, such as epi-isozizaene synthase and pentalenene synthase, as well as 2-methylisoborneol synthase, which processes a naturally occuring noncanonical isoprenoid substrate [ 1 , 2 ]. As with other enzymes with the 'terpenoid synthase fold', they have two conserved metal binding motifs, proposed to coordinate Mg2+ ion-bridged binding of the diphosphate moiety of FPP to the enzymes. Metal-triggered substrate ionization initiates catalysis, and the alpha-barrel active site serves as a template to channel and stabilize the conformations of reactive carbocation intermediates through a complex cyclization cascade. These enzymes function in the monomeric form and are found mostly in fungi and bacteria [ 3 , 4 ].

1. Structure of epi-isozizaene synthase from Streptomyces coelicolor A3(2), a platform for new terpenoid cyclization templates. Biochemistry 49, 1787-97
2. Structure of 2-Methylisoborneol Synthase from Streptomyces coelicolor and Implications for the Cyclization of a Noncanonical C-Methylated Monoterpenoid Substrate. Biochemistry 51, 3011-20
3. Crystal structure determination of aristolochene synthase from the blue cheese mold, Penicillium roqueforti. J. Biol. Chem. 275, 25533-9
4. Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology. Science 277, 1820-4