Kauniolide synthase is a P450 with unusual hydroxylation and cyclization-elimination activity
Liu, Qing (University of Copenhagen. Department of Plant and Environmental Sciences)
Beyraghdar Kashkooli, Arman (Wageningen University and Research. Laboratory of Plant Physiology)
Manzano, David (Centre de Recerca en Agrigenòmica)
Pateraki, Irini (University of Copenhagen. Department of Plant and Environmental Sciences)
Richard, Lea (Wageningen University and Research. Laboratory of Plant Physiology)
Kolkman, Pim (Wageningen University and Research. Laboratory of Plant Physiology)
Lucas, Maria Fátima (Barcelona Supercomputing Center)
Guallar, Victor (Institució Catalana de Recerca i Estudis Avançats)
de Vos, Ric C. H. (Wageningen University and Research. Wageningen Plant Research)
Franssen, Maurice C. R. (Wageningen University. Laboratory of Organic Chemistry)
van der Krol, Alexander (Wageningen University and Research. Laboratory of Plant Physiology)
Bouwmeester, Harro (University of Amsterdam. Swammerdam Institute for Life Sciences)

Data:	2018
Resum:	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.
Ajuts:	European Commission 227448
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biosynthetic Pathways ; Cyclization ; Cytochrome P-450 Enzyme System ; Hydroxylation ; Molecular Docking Simulation ; Saccharomyces cerevisiae ; Sesquiterpenes ; Tanacetum ; Tobacco
Publicat a:	Nature communications, Vol. 9 (November 2018) , art. 4657, ISSN 2041-1723

DOI: 10.1038/s41467-018-06565-8
PMID: 30405138

13 p, 1.7 MB

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