2026-04-17T12:00:11Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4388492024-10-31T03:39:09Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Liu, Qing author Beyraghdar Kashkooli, Arman author Manzano, David author Pateraki, Irini author Richard, Lea author Kolkman, Pim author Lucas, Maria Fátima author Guallar, Victor author de Vos, Ric C. H. author Franssen, Maurice C. R. author van der Krol, Alexander author Bouwmeester, Harro author 2018 Guaianolides are an important class of sesquiterpene lactones with unique biological and pharmaceutical properties. They have been postulated to be derived from germacranolides, but for years no progress has been made in the elucidation of their biosynthesis that requires an unknown cyclization mechanism. Here we demonstrate the isolation and characterization of a cytochrome P450 from feverfew (Tanacetum parthenium), kauniolide synthase. Kauniolide synthase catalyses the formation of the guaianolide kauniolide from the germacranolide substrate costunolide. Unlike most cytochrome P450s, kauniolide synthase combines stereoselective hydroxylation of costunolide at the C3 position, with water elimination, cyclization and regioselective deprotonation. This unique mechanism of action is supported by in silico modelling and docking experiments. The full kauniolide biosynthesis pathway is reconstructed in the heterologous hosts Nicotiana benthamiana and yeast, paving the way for biotechnological production of guaianolide-type sesquiterpene lactones. Biosynthetic Pathways Cyclization Cytochrome P-450 Enzyme System Hydroxylation Molecular Docking Simulation Saccharomyces cerevisiae Sesquiterpenes Tanacetum Tobacco Kauniolide synthase is a P450 with unusual hydroxylation and cyclization-elimination activity