Triterpenoids triterpene synthases

Chimeric enzymes constructed fi"om two different angiosperms (Panax ginseng, Araliaceae, and Arabidopsis thaliana, Brassicaceae) yielded mixtures of triterpenoids, p-amirin and lupeol, at a composition depending on the particular chimera methyl scrambling was observed for lupeol only (Kushiro 1999). A few differences in the amino acids at the active site are responsible for these effects. This implies that the high variety of plant triterpenoids owes more to chimeric enzymes than product-specific triterpene synthases. It was proposed that these chimeric enzymes act as multifunctional triterpene synthases (Kushiro 1999). 

Terpene synthesis in nature is a complex process involving successive electrophilic additions followed by a variety of skeletal rearrangements, including those of the Wagner-Meerwein variety. These reactions are typically catalyzed by enzymes and are responsible for the wide array of structural diversity in these compounds, including 6-6-6-5 tetracycles, 6-6-6-6-5 pentacycles, 6-6-6-6-6 pentacycles, and the less abundant acyclic, monocyclic, bicyclic, tricyclic, and hexacyclic triterpenoids. Each of the more than 100 triterpene skeletons identified in nature are formed through the involvement of several multifunctional triterpene synthases. 

Class 11 terpene cyclases are known for the cycUzation of di-, sester-, and triterpenoids. Prominent examples of triterpene cyclases are the human lanosterol synthase (oxidosqualene cyclase, OSC) and the squalene/hopene cyclase (SHC) firom A. acidocaldarius [1]. Both enzymes have a py-domain architecture (Fig. 87.15a). The p-domain exhibits a highly regular Oe-Oe barrel structure with six inner and six outer helices surrounding a central cavity (Fig. 87.15b) [198,199, 208]. The y-domains may have originated from the p-domains by gene duplicatimi... 

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