206
13
What You Will Learn in This Chapter
Besides the classical groups of alkaloids, phenylpropanoids and isoprenoids, several other
biosynthesis pathways produce important classes of secondary metabolites. These include
especially cannabinoids and fatty acid-derived compounds.
13.1 Quinone
Naphthoquinone biosynthesis can use chorismate, a phenylpropanoid, as a precursor (see above, 7 Chap. 11). The addition of 2-oxoglutarate leads to the intermediate
2- succinylbenzoate. In addition, the shikimate/mevalonate or polyketide pathway can
be utilized for modifications. 2-carboxy-1,4-naphthoquinol is a branch point leading to
the biosynthesis of phylloquinone (vitamin K1), two-ring naphthoquinones such as lawsone (red-orange pigment present in the leaves of the henna plant, Lawsonia inermis),
juglone (a phytotoxic and therefore allelopathic compound mainly found in walnut,
Juglans regia) and the three-ring anthraquinones such as alizarin (a red dye isolated
from Rubiaceae).
13.2 Polyketide (e.g. Cannabinoids)
Polyketides are structurally and functionally diverse secondary metabolites produced in
bacteria, fungi, and plants. They are synthesized from a starter unit, usually an acyl-CoA,
fused sequentially with malonyl-CoA and catalysed by polyketide synthases (PKSs), a reaction similar to fatty acid biosynthesis. PKSs are large, multifunctional enzymes with several enzymatic domains able to generate complex structures. Intramolecular cyclation can
occur by Claisen condensation, aldol condensation, and lactonization. Additionally, units
can be added, such as acetate, malonate, propionate, butyrate, and glycolate. Polyketide
synthesis in fungi or bacteria can be combined with non-ribosomal peptide synthesis,
where carboxylic and amino acid extender units are sequentially added to a growing acyl
or peptidyl chain (similar to ergot biosynthesis, see above, 7 Sect. 12.2). Polyketides from
bacteria are often used as antibiotics or immunosuppressants, e.g. lovastatin (p resent in
fermented tea or rice, used for the treatment of hypercholesterolemia due to an inhibition
of the HMG-CoA-Reductase) and actinorhodin (an antibiotic).
Phytocannabinoids are terpeno-phenolic compounds predominantly produced in
Cannabis sativa (Cannabaceae). The precursors of cannabinoids are derived from the
polyketide pathway starting with the short-chain fatty acid hexanoate via hexanoyl-CoA
(Flores-Sanchez and Verpoorte 2008; Stout et al. 2012). Sequential aldol condensation
with three molecules of malonyl-CoA leads to olivetolic acid with the help of the polyketide
synthase olivetolic acid cyclase (OAC)(Gagne et al. 2012). A prenyltransferase adds GPP
derived from the MEP pathway leading to the formation of cannabigerolic acid (CBGA)
(. Fig. 13.1). Oxidocyclases are responsible for the diversity. The main compounds are
Δ 9 - tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA). The decarboxylated derivatives are Δ 9 -tetrahydrocannabinol (THC),
cannabidiol (CBD) and cannabichromene (CBC) (Raharjo et al. 2004). The decarboxylation occurs non-enzymatically by harvesting or heating. The Cannabis variety used for
textiles contains the cannabinoids CBDA and CBCA at high concentrations in contrast to
THCA (Kim and Mahlberg 1997; Kim and Mahlberg 2003). CBCA accumulates mainly
Chapter 13 · Minor Groups of Secondary Metabolites
13
What You Will Learn in This Chapter
Besides the classical groups of alkaloids, phenylpropanoids and isoprenoids, several other
biosynthesis pathways produce important classes of secondary metabolites. These include
especially cannabinoids and fatty acid-derived compounds.
13.1 Quinone
Naphthoquinone biosynthesis can use chorismate, a phenylpropanoid, as a precursor (see above, 7 Chap. 11). The addition of 2-oxoglutarate leads to the intermediate
2- succinylbenzoate. In addition, the shikimate/mevalonate or polyketide pathway can
be utilized for modifications. 2-carboxy-1,4-naphthoquinol is a branch point leading to
the biosynthesis of phylloquinone (vitamin K1), two-ring naphthoquinones such as lawsone (red-orange pigment present in the leaves of the henna plant, Lawsonia inermis),
juglone (a phytotoxic and therefore allelopathic compound mainly found in walnut,
Juglans regia) and the three-ring anthraquinones such as alizarin (a red dye isolated
from Rubiaceae).
13.2 Polyketide (e.g. Cannabinoids)
Polyketides are structurally and functionally diverse secondary metabolites produced in
bacteria, fungi, and plants. They are synthesized from a starter unit, usually an acyl-CoA,
fused sequentially with malonyl-CoA and catalysed by polyketide synthases (PKSs), a reaction similar to fatty acid biosynthesis. PKSs are large, multifunctional enzymes with several enzymatic domains able to generate complex structures. Intramolecular cyclation can
occur by Claisen condensation, aldol condensation, and lactonization. Additionally, units
can be added, such as acetate, malonate, propionate, butyrate, and glycolate. Polyketide
synthesis in fungi or bacteria can be combined with non-ribosomal peptide synthesis,
where carboxylic and amino acid extender units are sequentially added to a growing acyl
or peptidyl chain (similar to ergot biosynthesis, see above, 7 Sect. 12.2). Polyketides from
bacteria are often used as antibiotics or immunosuppressants, e.g. lovastatin (p resent in
fermented tea or rice, used for the treatment of hypercholesterolemia due to an inhibition
of the HMG-CoA-Reductase) and actinorhodin (an antibiotic).
Phytocannabinoids are terpeno-phenolic compounds predominantly produced in
Cannabis sativa (Cannabaceae). The precursors of cannabinoids are derived from the
polyketide pathway starting with the short-chain fatty acid hexanoate via hexanoyl-CoA
(Flores-Sanchez and Verpoorte 2008; Stout et al. 2012). Sequential aldol condensation
with three molecules of malonyl-CoA leads to olivetolic acid with the help of the polyketide
synthase olivetolic acid cyclase (OAC)(Gagne et al. 2012). A prenyltransferase adds GPP
derived from the MEP pathway leading to the formation of cannabigerolic acid (CBGA)
(. Fig. 13.1). Oxidocyclases are responsible for the diversity. The main compounds are
Δ 9 - tetrahydrocannabinolic acid (THCA), cannabidiolic acid (CBDA) and cannabichromenic acid (CBCA). The decarboxylated derivatives are Δ 9 -tetrahydrocannabinol (THC),
cannabidiol (CBD) and cannabichromene (CBC) (Raharjo et al. 2004). The decarboxylation occurs non-enzymatically by harvesting or heating. The Cannabis variety used for
textiles contains the cannabinoids CBDA and CBCA at high concentrations in contrast to
THCA (Kim and Mahlberg 1997; Kim and Mahlberg 2003). CBCA accumulates mainly
Chapter 13 · Minor Groups of Secondary Metabolites