162
10
present in GGPP whereas class II diterpene cyclases leave this bond intact to be modified
by subsequently acting class I diterpene synthases. Both belong to the enzymatic group
of TPS (7 Box. 10.1). In the most common pathway GGPP gives rise to the bicyclic entcopalyl pyrophosphate via a class II cyclase which forms the bicyclic labdane carbon skeleton (Peters 2010). A type I cyclase closes the third ring leading to ent-kaurene, which is a
precursor for the hormone gibberellin.
Other components derived from ent-kaurene are steviol, an intermediate for the biosynthesis of the sweetener stevioside (which is a glycosylated derivative) found in Stevia
rebaudiana; cafestol and kahweol, which are found in coffee, adding to the effect of caffeine; and kauralexins, which are phytoalexins from maize. Furthermore, diterpene resin
acids are characterized by tricyclic parent skeletons and are major components of the
defense system of pine trees, often accumulating in the resin ducts of the phloem and cortex. In addition, grayanotoxins, toxins found in rhododendrons and other Ericaceae, are
suggested to derive from ent-kaurene. The toxins can also be found in the nectar, which
when used by honey bees can lead to contamination of the honey (“mad honey”) (see
7 Box 1.1). Grayanotoxins can bind to the group II receptor site in voltage-gated sodium
channels within the cell (see . Fig. 4.2b). Forskolin also has a labdane skeleton formed via
Copal 8-ol pyrophosphate from the intermediate 13R-manoyl oxide. This compound is
found in Plectranthus barbatus (Syn. Coleus forskohlii, Lamiaceae), where it accumulates
in the root cork. It has been shown to activate the enzyme adenylyl cyclase and thereby
increases intracellular levels of cAMP in humans.
Salvinorin A biosynthesis in Salvia divinorum (Lamiaceae), a κ-opiate receptor agonist, is not completely understood but seems to happen via the formation of (-)-kolavenyl
diphosphate (Chen et al. 2017). Salvinorin A is a highly oxidized diterpene that is also
methylated and acetylated. Peltate glandular trichomes were identified as the major site of
salvinorin A accumulation in S. divinorum (Siebert 2004).
Derivatives of class I diterpene synthases are, for example, casbene, the antifungal
component in castor bean (Ricinus communis). Bicyclic diterpenes can be further changed
into polycyclic diterpenes, such as the pentacyclic ryanodine (from Ryania speciosa,
Salicaceae), which interacts with the ryanodine receptor. Others are the tetracyclic phorbol ester present in the latex of many Euphorbiaceae and Thymelaeaceae, which mimics
the action of diacylglycerol, and resiniferatoxin, which is present in the latex of Euphorbia
resinifera (Euphorbiaceae) and hyperactivates the transient vanilloid receptor 1 (TRPV1).
Other diterpenoids are formed by macrocyclic-forming steps leading to cembranes and
taxanes. Taxol, sold as paclitaxel, is a known anticancer medication.
The diterpene synthases mostly produce olefins, which are highly hydrophobic.
Introduction of oxygen increases the solubility and adds hydrogen-bonding potential, a
step catalyzed by Cyt P450 enzymes. Some of the compounds, especially if they act as
defense compounds, are produced in glandular trichomes such as cembratrieneols in
tobacco or carnosol and carnosic acid in rosemary and sage, which seems to have antioxidative and antimicrobial properties.
10.4 Tetraterpene (From MEP Pathway, C40)
Tetraterpenes are produced by the fusion of two GGPP, usually via head-to-head condensation (Ruiz-Sola and Rodriguez-Concepcion 2012; Nisar et al. 2015). This leads to the
formation of phytoene by the phytoensynthase. The next step leads to the formation of
Chapter 10 · Terpenes and Terpenoids
10
present in GGPP whereas class II diterpene cyclases leave this bond intact to be modified
by subsequently acting class I diterpene synthases. Both belong to the enzymatic group
of TPS (7 Box. 10.1). In the most common pathway GGPP gives rise to the bicyclic entcopalyl pyrophosphate via a class II cyclase which forms the bicyclic labdane carbon skeleton (Peters 2010). A type I cyclase closes the third ring leading to ent-kaurene, which is a
precursor for the hormone gibberellin.
Other components derived from ent-kaurene are steviol, an intermediate for the biosynthesis of the sweetener stevioside (which is a glycosylated derivative) found in Stevia
rebaudiana; cafestol and kahweol, which are found in coffee, adding to the effect of caffeine; and kauralexins, which are phytoalexins from maize. Furthermore, diterpene resin
acids are characterized by tricyclic parent skeletons and are major components of the
defense system of pine trees, often accumulating in the resin ducts of the phloem and cortex. In addition, grayanotoxins, toxins found in rhododendrons and other Ericaceae, are
suggested to derive from ent-kaurene. The toxins can also be found in the nectar, which
when used by honey bees can lead to contamination of the honey (“mad honey”) (see
7 Box 1.1). Grayanotoxins can bind to the group II receptor site in voltage-gated sodium
channels within the cell (see . Fig. 4.2b). Forskolin also has a labdane skeleton formed via
Copal 8-ol pyrophosphate from the intermediate 13R-manoyl oxide. This compound is
found in Plectranthus barbatus (Syn. Coleus forskohlii, Lamiaceae), where it accumulates
in the root cork. It has been shown to activate the enzyme adenylyl cyclase and thereby
increases intracellular levels of cAMP in humans.
Salvinorin A biosynthesis in Salvia divinorum (Lamiaceae), a κ-opiate receptor agonist, is not completely understood but seems to happen via the formation of (-)-kolavenyl
diphosphate (Chen et al. 2017). Salvinorin A is a highly oxidized diterpene that is also
methylated and acetylated. Peltate glandular trichomes were identified as the major site of
salvinorin A accumulation in S. divinorum (Siebert 2004).
Derivatives of class I diterpene synthases are, for example, casbene, the antifungal
component in castor bean (Ricinus communis). Bicyclic diterpenes can be further changed
into polycyclic diterpenes, such as the pentacyclic ryanodine (from Ryania speciosa,
Salicaceae), which interacts with the ryanodine receptor. Others are the tetracyclic phorbol ester present in the latex of many Euphorbiaceae and Thymelaeaceae, which mimics
the action of diacylglycerol, and resiniferatoxin, which is present in the latex of Euphorbia
resinifera (Euphorbiaceae) and hyperactivates the transient vanilloid receptor 1 (TRPV1).
Other diterpenoids are formed by macrocyclic-forming steps leading to cembranes and
taxanes. Taxol, sold as paclitaxel, is a known anticancer medication.
The diterpene synthases mostly produce olefins, which are highly hydrophobic.
Introduction of oxygen increases the solubility and adds hydrogen-bonding potential, a
step catalyzed by Cyt P450 enzymes. Some of the compounds, especially if they act as
defense compounds, are produced in glandular trichomes such as cembratrieneols in
tobacco or carnosol and carnosic acid in rosemary and sage, which seems to have antioxidative and antimicrobial properties.
10.4 Tetraterpene (From MEP Pathway, C40)
Tetraterpenes are produced by the fusion of two GGPP, usually via head-to-head condensation (Ruiz-Sola and Rodriguez-Concepcion 2012; Nisar et al. 2015). This leads to the
formation of phytoene by the phytoensynthase. The next step leads to the formation of
Chapter 10 · Terpenes and Terpenoids