Advances in the Enzymology of Monoterpene Cyclization Reactions

Abstract

Monoterpene cyclases catalyze the electrophilic isomerization–cyclization of the C10 prenyl diphosphate, geranyl diphosphate (GPP), to generate a diverse selection of monoterpenes. This tightly coupled reaction proceeds through the tertiary, enzyme-bound intermediate, linalyl diphosphate (LPP), which following internal addition (cyclization) may undergo numerous rearrangements and secondary cyclizations before reaction termination by deprotonation or nucleophile capture. This chapter provides a detailed overview of the reaction chemistry, and the stereochemistry and cyclization mechanisms of monoterpene cyclases. A survey of the molecular biology of monoterpene cyclases is presented taking into account their evolutionary relatedness and their potential diversity based on recent genome sequencing projects. General structural themes for terpene cyclases are presented before the structures of (−)-limonene synthase (LS), (+)-bornyl diphosphate synthase ((+)-BS), and 1,8-cineole synthase (CS) are presented in the context of each of their respective reaction mechanisms.