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 at the molecular level. Since costunolide is the simplest type of 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 FPP is converted to germacrene A by a terpene synthase, the gene of which is already known, we recently identified the gene of germacrene A oxidase that catalyzes 3 step-oxidation from germacrene A to GAA. Since the last step from GAA to costunolide is reported as a P450 reaction, we are trying to isolate the corresponding P450 gene using sunflower trichome EST library and lettuce EST information. Although the difficulty was to obtain GAA, the substrate of the targeted P450, we overcame it with the aid of synthetic biological approach; i.e., we expressed GAA biosynthetic genes in engineered FPP high-producing yeast to produce GAA.
