8.2.4 Geranyl Pyrophosphate:Olivetolate
Geranyltransferase
CBGA is an important cannabinoid as it is the central precursor of various
cannabinoids. This cannabinoid is formed by the condensation between OLA and
geranyl pyrophosphate (GPP), and catalyzed by the prenyltransferase geranyl
pyrophosphate:olivetolate geranyltransferase (GOT) (Fig.8.9). The excellent
enzymological study conducted by Fellermeier and Zenk ( 1998 ) identified this
novel prenyltransferase in the expanding leaves ofC. sativa. With respect to sub-
strate specificity, GOT preferred GPP as the prenyl donor. Interestingly, olivetol,
the decarboxylation product of OLA (the prenyl acceptor), was not a substrate for
this enzyme. Therefore, the carboxyl group is crucial for the GOT reaction. This is
reasonable because not all of the downstream cannabinoid synthases (THCA,
CBDA, and CBCA synthase) can accept cannabigerol as a substrate (Taura et al.
1995 , 1996 ; Morimoto et al. 1998 ).
Professor Zenk’s group also reported the biosynthetic origin of the phenolic and
terpenic portion of cannabinoids based on incorporation experiments using
(^13) C-labeled glucose (Fellermeier et al. 2001 ). They clearly demonstrated that the
alkylphenol moieties of cannabinoids are derived from a polyketide pathway,
whereas monoterpene moieties are completely or predominantly from the
methylerythritol 4-phosphate (MEP) pathway. Because the MEP pathway generally
operates in the plastids of higher plants (Eisenreich et al. 1998 ; Rodríguez-
Concepción and Boronat 2015 ), GOT as well as GPP synthase would function in
the plastids ofC. sativa. If so, CBGA would be transported from plastids to tri-
chome secretory cavities for the oxidocyclization reactions and production of the
final products such as THCA.
Recently, Page’s group reported the cDNA cloning and characterization of a
C. sativaprenyltransferase (CsPT-1) (Page and Boubakir 2011 ). The recombinant
CsPT-1 synthesized CBGA from OLA and GPP as reported for GOT, together with
small amount of a byproduct 5-geranyl olivetolate. The primary structure of CsPT-1
Fig. 8.9 The reaction catalyzed by geranyl pyrophosphate: olivetolate geranyltransferase (GOT).
OLAolivetolic acid;CBGAcannabigerolic acid
194 S. Sirikantaramas and F. Taura