Trichodiene Synthase. Enzymatic Formation of Multiple Sesquiterpenes by Alteration of the Cyclase Active Site

摘要

Sesquiterpene syntheses are versatile catalysts which together are responsible for the formation of more than 200 distinct sesquiterpene carbon skeletons. Intriguingly, each individual synthase is capable of converting the universal acyclic precursorfarnesyl diphosphate (FPP, 1) to a distinct sesquiterpene, all the while utilizing a common mechanism involving ionization of the allylic pyrophosphate ester followed by a precise sequence of intramolecular electrophilic addition reactions. A major determinant of the structure and stereochemistry of the ultimately formed sesquiterpene is believed to be the precise folding of the FPP substrate at the cyclase active site. Although many of the mechanistic and stereochemical features of this model have beenverified by a wealth of isotopic labeling experiments, little is known about the active site of any cyclase or the manner in which a sesquiterpene synthase imposes a particular conformation on its highly lipophilic substrate, precisely controls the resulting cascade of electrophilic cyclizatipns, and ultimately quenches the positive charge.