Structural Biology of Template-Directed Catalysis by Terpene Synthases

Abstract

More than 80,000 terpenes have been identified to date, making this the largest known family of natural products. The molecular basis of chemodiversity is rooted in terpene synthases. This enzyme family consists of prenyltransferases that link linear isoprenoids to isoprenoid or nonisoprenoid cosubstrates, and terpene cyclases that utilize linear isoprenoids as substrates for complex multistep cyclization reactions. The era of terpene synthase structural biology began with the first X-ray crystal structure determinations of terpene synthases more than 20years ago—a class I prenyltransferase, two class I terpene cyclases, and one class II terpene cyclase. Since then, myriad structural, enzymological, and protein engineering studies have shown how these enzymes catalyze the most complex carbon–carbon bond-forming reactions in nature. This article focuses specifically on the past, present, and future of class I terpene synthases.