Abstract
Sesquiterpene lactone (STL) is a characteristic secondary metabolite most often found in Asteraceae family. Despite the pharmaceutical importance of STLs, most of their biosynthesis remains unknown. Since costunolide is the simplest STL and is believed to be a central precursor of diverse STLs, we have focused on the understanding of costunolide biosynthesis as an important first step for STL biochemistry. Costunolide is biosynthesized from farnesyl diphosphate (FPP) via germacrene A and germacrene A acid (GAA). While the biosynthetic genes of GAA from FPP have been identified, P450 gene which is responsible for lactone ring formation from GAA to costunolide was unknown. By utilizing sunflower capitate glandular trichome EST library, we identified a novel P450 gene which can hydroxylate GAA, and the use of this gene information led us to successful isolation of costunolide synthase gene from lettuce. Reconstitution of costunolide biosynthesis in engineered yeast enabled de novo biosynthesis of costunolide. The reaction products of the novel sunflower P450 and lettuce costunolide synthase give us a clue for better understanding of STL biosynthesis in Asteraceae family.
