Terpene synthase (TPS) (TPS)

Terpene synthases (TPS) are a vast superfamily of enzymes responsible for generating the structural diversity of terpenoids, the largest class of natural products found in nature (Tholl, 2006). These enzymes catalyze the complex cyclization and rearrangement of acyclic prenyl diphosphate precursors—such as geranyl diphosphate (GPP), farnesyl diphosphate (FPP), and geranylgeranyl diphosphate (GGPP)—into a wide array of hydrocarbon skeletons (Christianson, 2017). In humans, the most medically relevant terpene synthases are squalene synthase (FDFT1) and lanosterol synthase (LSS), which are pivotal in the cholesterol biosynthetic pathway (UniProt Consortium, 2023). Inhibition of these enzymes has been explored as a therapeutic strategy for managing hypercholesterolemia and preventing cardiovascular disease, offering a potential alternative or adjunct to statin therapy (Gao et al., 2012). Beyond human health, microbial terpene synthases are critical for the production of specialized metabolites and virulence factors, making them promising targets for the development of novel antibiotics and antiparasitic drugs (Pateraki et al., 2015). Additionally, terpene synthases are extensively utilized in metabolic engineering to produce high-value compounds, including the antimalarial drug artemisinin and the chemotherapeutic agent paclitaxel (Bohlmann & Keeling, 2008).

Other names

Terpene cyclaseTerpenoid cyclaseIsoprenoid synthasePrenyl cyclase

Competitive inhibition of the enzyme's active site, preventing the conversion of prenyl diphosphate precursors into cyclic or rearranged terpene products.