Cannabis sativa L. - Botany and Biotechnology

almost exclusively synthesized byC. sativa(Gertsch et al. 2010 ) and are valued as
promising therapeutics to treat several medical conditions (Stott and Guy 2004 ;Hill
et al. 2012 ; Velasco et al. 2012 ; Devinsky et al. 2014 ). The cannabinoid pathway
synthesizes at least 70 metabolites valued for their pharmacological properties
(ElSohly and Slade 2005 ). THCA is the major cannabinoid in marijuana cultivars
while cannabidiolic acid (CBDA) is the principal compound in hemp cultivars (van
Bakel et al. 2011 ; Weiblen et al. 2015 ; Fig.16.1). Cannabinoids are synthesized in
an acidic form (THCA and CBDA) that become decarboxylated into their neutral

Polyketide synthase (PKS)/

Olivetol synthase (OLS)

Aromatic

prenyltransferase

Hexanoyl-CoA synthetase/

Acyl-activating enzyme1 (CsAAE1)

3 x malonyl-CoA

THCA synthase

(THCAS) CBDA synthase

Geranyldiphosphate

CoA

Fatty acid

biosynthesis Hexanoic acid Hexanoyl-CoA

Olivetolic

acid (OLA)

Cannabigerolic

acid (CBGA)

Cannabidiolic

acid (CBDA)

Δ^9 -Tetrahydrocannabinolic

acid (THCA)

Cannabidiol

(CBD)

Δ^9 -Tetrahydrocannabinol

(THC)

Non-enzymatic

CO 2 decarboxylation CO 2

Olivetolic acid cyclase (OAC)

+

H 2 O 2

Fig. 16.1 Overview of the cannabinoid biosynthetic pathway that leads to the major cannabi-
noids, THCA and CBDA, and the non-enzymatic decarboxylation to THC and CBD. Modified
from Stout et al. 2012

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