Taxadiene synthase structure and evolution of modular architecture in terpene biosynthesis

The first step in the biosynthesis of the anticancer compound Taxol (paclitaxel) and many other natural C20 diterpenes is the cyclization of an isoprenoid, catalysed by taxadiene synthase. The X-ray crystal structure of this enzyme from the Pacific yew has now been determined. Its C-terminal catalytic domain binds and activates the substrate in a manner seen in class I terpenoid cyclases, but the N-terminal domain and a third 'insertion' domain adopt the fold of a class II terpenoid cyclase. This suggests that this enzyme could be the ancestral progenitor of all terpenoid cyclases.