Humulene cyclase

Terpene cyclase enzymes catalyze the cychzation of allylic pyrophosphate substrates to form carbocyclic products via car-bocation reaction intermediates. One well-studied example is pentalenene synthase (11, 12), which catalyzes the cychzation of farnesyl pyrophosphate to give pentalenene, whose reaction mechanism is shown in Fig. 15. Cychzation of farnesyl pyrophosphate is proposed to form an 11-membered intermediate, humulene, which is followed by a five-membered ring closure to form a bicychc tertiary carbocation. 1,2-Hydride migration followed by an additional five-membered ring closure gives a tricyclic carbocation, which gives pentalenene, at elimination. 

Two of the most common sesquiterpenes, humulene (10) and P-caryophyllene (11), were synthesized by a soluble enzyme preparation from leaves of sage (Salvia officinalis, Lamiaceae). Partial purification of the extracts allowed resolution of the two cyclizing activities. Both cyclases had molecular weights of 58,000 and depended on the presence of a divalent cation Mg " " was preferred (Cane, 1990). 

Dehal, S. S. and R. Croteau, Partial purification and characterization of two sesquiterpene cyclases from sage (Salvia officinalis) which catalyze the respective conversion of famesyl pyrophosphate to humulene and caryophyllene. Arch. Biochem. Biophys., 261, 346-356 (1988). 

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