Terpene synthase (TPS)

Terpene synthases (TPS) are a diverse superfamily of enzymes that catalyze the formation of complex cyclic and linear hydrocarbon scaffolds from acyclic prenyl diphosphate precursors. This process is the fundamental step in the biosynthesis of terpenes and terpenoids, the largest and most structurally varied class of natural products, which include essential compounds like cholesterol, steroid hormones, and fat-soluble vitamins. In humans, the most prominent member of this family is squalene synthase (FDFT1), which mediates the first committed step in the cholesterol biosynthetic pathway by condensing two molecules of farnesyl diphosphate. Because they regulate sterol flux, terpene synthases are major therapeutic targets for the treatment of hypercholesterolemia and cardiovascular disease. Unlike statins, TPS inhibitors such as lapaquistat target a downstream point in the pathway, potentially avoiding the side effects associated with depleting upstream metabolites like coenzyme Q10 and dolichol. Additionally, microbial terpene synthases are being explored as targets for novel antimicrobial drugs to disrupt essential metabolic processes in pathogens.

Other names

Terpene cyclaseIsoprenoid synthaseSqualene synthasePrenyl cyclaseFarnesyl-diphosphate farnesyltransferase

Competitive or non-competitive inhibition of the enzyme's catalytic site to prevent the cyclization or condensation of prenyl diphosphate precursors, thereby blocking the synthesis of downstream sterols or terpenes.