Kauniolide synthase is a P450 with unusual hydroxylation and cyclization-elimination activity

Qing Liu, Arman Beyraghdar Kashkooli (), David Manzano, Irini Pateraki, Lea Richard, Pim Kolkman, Maria Fátima Lucas, Victor Guallar, Ric C.H. de Vos, Maurice C. R. Franssen, Alexander van der Krol and Harro Bouwmeester ()
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Qing Liu: Wageningen University and Research
Arman Beyraghdar Kashkooli: Wageningen University and Research
David Manzano: Centre for Research in Agricultural Genomics (CRAG) (CSIC-IRTA-UAB-UB), 08193
Irini Pateraki: University of Copenhagen
Lea Richard: Wageningen University and Research
Pim Kolkman: Wageningen University and Research
Maria Fátima Lucas: Barcelona Supercomputing Center (BSC)
Victor Guallar: Barcelona Supercomputing Center (BSC)
Ric C.H. de Vos: Wageningen University and Research
Maurice C. R. Franssen: Wageningen University
Alexander van der Krol: Wageningen University and Research
Harro Bouwmeester: Wageningen University and Research

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-06565-8

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