THC usually accumulates at a quite a low level in the fresh leaves of
C. sativa and is shown to be derived artificially from the acidic cannabinoid Δ
1-tetrahydrocannabinolic acid (THCA) by non-enzymatic decarboxylation during storage and smoking (Yamauchi
et al., 1967; Kimura & Okamoto, 1970). Our biosynthetic studies demonstrated that THCA, which had been believed to be formed through isomerization of cannabidiolic acid (CBDA), was actually derived from cannabigerolic acid (CBGA; Taura
et al., 1995, 1996; Fig. 1
). Furthermore, we identified and purified an oxidoreductase named THCA synthase which catalyzes THCA biosynthesis in rapidly expanding leaves of C. sativa (Taura et al., 1995). Biochemical investigation using the purified enzyme established that THCA synthase oxidatively cyclizes the monoterpene moiety of CBGA to stereospecifically form THCA (Taura et al., 1995; Sirikantaramas et al., 2004). Because enzymes catalyzing such an oxidocyclization have been not identified to date, it is of great interest to precisely reveal the structure of THCA synthase and to understand the mechanism of the THCA synthase reaction.
THCA biosynthesis. THCA synthase catalyzes oxidative cyclization of the monoterpene moiety of CBGA to form THCA. THC is derived from THCA by non-enzymatic decarboxylation.