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Information on EC 5.5.1.12 - copalyl diphosphate synthase
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EC Tree
5.5.1.12 copalyl diphosphate synthaseIUBMB Comments
In some plants, such as Salvia miltiorrhiza, this enzyme is monofunctional. In other plants this activity is often a part of a bifunctional enzyme. For example, in Selaginella moellendorffii this activity is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.131, miltiradiene synthase, while in the tree Abies grandis (grand fir) it is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.18, abietadiene synthase.
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Word Map
- 5.5.1.12
-
geranylgeranyl
- salvia
- gibberellin
-
diterpenoids
- miltiorrhiza
- tanshinone
- ent-kaurene
- miltiradiene
-
kaurene
-
carbocation
-
+-copalyl
-
protonation-initiated
-
ent-copalyl
-
abietane-type
- cryptotanshinone
-
ditpss
- ferruginol
-
e,e,e-geranylgeranyl
-
manoyl
- dihydrotanshinone
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abietane
-
labdane
- phaeosphaeria
-
norditerpenoids
- steviol
-
labdane-related
-
abietic
- synthesis
The enzyme appears in viruses and cellular organisms
Synonyms
copalyl diphosphate synthase, abietadiene synthase, smcps, smcps1, bifunctional diterpene cyclase, class ii diterpene synthase, class ii ditps, (+)-copalyl diphosphate synthase, rocps1, mvcps3, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(-)-abietadiene synthase
-
-
-
-
abietadiene cyclase
-
-
-
-
abietadiene synthase
bifunctional LAS-type diTPS
class II diterpene synthase
class II diTPS
CPS1
CPS2
cyclase, abietadiene
-
-
-
-
ISO
isopimaradiene synthase-type diTPS
LAS
levopimaradiene/abietadiene synthase-type diTPS
SmCPS1
SmCPS2
additional information
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
geranylgeranyl diphosphate = (+)-copalyl diphosphate
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclization
-
bifunctional enzyme that catalyzes two sequential cyclization reactions in distinct active sites
intramolecular cyclization
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-
-
-
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PATHWAY SOURCE
PATHWAYS
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SYSTEMATIC NAME
IUBMB Comments
(+)-copalyl-diphosphate lyase (decyclizing)
In some plants, such as Salvia miltiorrhiza, this enzyme is monofunctional. In other plants this activity is often a part of a bifunctional enzyme. For example, in Selaginella moellendorffii this activity is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.131, miltiradiene synthase, while in the tree Abies grandis (grand fir) it is catalysed by a bifunctional enzyme that also catalyses EC 4.2.3.18, abietadiene synthase.
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CAS REGISTRY NUMBER
COMMENTARY
157972-08-2
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate
copalyl diphosphate
-
class II terpene synthase reaction
-
-
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
-
-
-
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
BDTC-like enzyme, miltiradiene synthase converts geranylgeranyl diphosphate to a diterpene hydrocarbon product with a molecular mass of 272 Da. Mutation in the type-B active motif of BDTC-like enzyme miltiradiene synthase, D611G/D612G, abolishes the cyclase activity, whereas (+)-copalyl diphosphate, the reaction intermediate from the conversion of geranylgeranyl diphosphate to the hydrocarbon product, rescues the cyclase activity of the mutant to form a diterpene hydrocarbon. Another mutant lacking type-A activity, D391G/D392G, accumulates copalyl diphosphate as the reaction intermediate
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-
?
additional information
?
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bifunctional enzyme that catalyzes two sequential cyclizations of geranylgeranyl diphosphate to isopimara-7,15-diene
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-
?
additional information
?
-
the enzyme shows substrate specificity, reaction product analysis by GC-MS. MvCPS3 does not produce ent-CPP, reaction of EC 5.5.1.13
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-
?
additional information
?
-
-
the enzyme shows substrate specificity, reaction product analysis by GC-MS. MvCPS3 does not produce ent-CPP, reaction of EC 5.5.1.13
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-
?
additional information
?
-
abietadiene synthase (PaLAS) is a bifunctional terpene synthase that catalyzes both class I and class II reactions, i.e. formation of (+)-copalyl diphosphate from geranylgeranyl diphosphate (EC 5.5.1.12, class II diTPS), and formation of abieta-8(14),12-diene from (+)-copalyl diphosphate (cf. EC 4.2.3.32, class I diTPS)
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-
?
additional information
?
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the bifunctional diterpene synthase isopimara-7, 15-diene synthase (diTPS-ISO) catalyzes the cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate and the formation of isopimara-7,15-diene from (+)-copalyl diphosphate (cf. EC 4.2.3.44). Compound identification and quantification by GC-MS analysis
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-
?
additional information
?
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gymnosperm diterpene synthases of diterpene resin acid biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of geranylgeranyl diphosphate followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. The bifunctional jack pine and lodgepole pine LAS enzymes demonstrated that the class I active sites of monofunctional proteins can use the (+)-copalyl diphosphate intermediate produced by the class II active site of the bifunctional enzymes, overview
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-
?
additional information
?
-
gymnosperm diterpene synthases of diterpene resin acid biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of geranylgeranyl diphosphate followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. The bifunctional jack pine and lodgepole pine LAS enzymes demonstrated that the class I active sites of monofunctional proteins can use the (+)-copalyl diphosphate intermediate produced by the class II active site of the bifunctional enzymes, overview
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-
?
additional information
?
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miltiradiene synthesis reaction with geranylgeranyl diphosphate to miltiradiene, EC 4.2.3.131, via (+)-copalyl diphosphate intermediate, not ent-copalyl diphosphate. The enzyme catalyzes the successive two-step type-B (protonation-initiated cyclization) and type-A (ionization-initiated cyclization) reactions of geranylgeranyl diphosphate. The two aspartate-rich motifs, 389DIDD and 611DDLMD, that are required for the type-B and type-A cyclization reactions, respectively. Product analysis by GC-MS and NMR spectroscopy
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-
?
additional information
?
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-
miltiradiene synthesis reaction with geranylgeranyl diphosphate to miltiradiene, EC 4.2.3.131, via (+)-copalyl diphosphate intermediate, not ent-copalyl diphosphate. The enzyme catalyzes the successive two-step type-B (protonation-initiated cyclization) and type-A (ionization-initiated cyclization) reactions of geranylgeranyl diphosphate. The two aspartate-rich motifs, 389DIDD and 611DDLMD, that are required for the type-B and type-A cyclization reactions, respectively. Product analysis by GC-MS and NMR spectroscopy
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-
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate
copalyl diphosphate
-
class II terpene synthase reaction
-
-
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
-
-
-
?
additional information
?
-
abietadiene synthase (PaLAS) is a bifunctional terpene synthase that catalyzes both class I and class II reactions, i.e. formation of (+)-copalyl diphosphate from geranylgeranyl diphosphate (EC 5.5.1.12, class II diTPS), and formation of abieta-8(14),12-diene from (+)-copalyl diphosphate (cf. EC 4.2.3.32, class I diTPS)
-
-
?
additional information
?
-
gymnosperm diterpene synthases of diterpene resin acid biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of geranylgeranyl diphosphate followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. The bifunctional jack pine and lodgepole pine LAS enzymes demonstrated that the class I active sites of monofunctional proteins can use the (+)-copalyl diphosphate intermediate produced by the class II active site of the bifunctional enzymes, overview
-
-
?
additional information
?
-
gymnosperm diterpene synthases of diterpene resin acid biosynthesis are bifunctional enzymes that catalyze the initial bicyclization of geranylgeranyl diphosphate followed by rearrangement of a (+)-copalyl diphosphate intermediate at two discrete class II and class I active sites. The bifunctional jack pine and lodgepole pine LAS enzymes demonstrated that the class I active sites of monofunctional proteins can use the (+)-copalyl diphosphate intermediate produced by the class II active site of the bifunctional enzymes, overview
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Mg2+
Mn2+
Mg2+
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terpene synthases (TPS) require divalent metal ion co-factors, typically magnesium
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Tuberculosis
Crystal Structure and Mechanistic Molecular Modeling Studies of Mycobacterium tuberculosis Diterpene Cyclase Rv3377c.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
geranylgeranyl diphosphate
-
mutant T769A, value not determined
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
geranylgeranyl diphosphate
-
mutant T769A, value below 10000
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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-
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brenda
contains 18 different amino acid sequence of copalyl diphosphate synthase, CPS
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brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
additional information
transcript levels of MvCPS3 are 28fold higher in leaves compared with flowers
brenda
additional information
-
transcript levels of MvCPS3 are 28fold higher in leaves compared with flowers
brenda
additional information
quantitative RT-PCR expression analysis on whole leaves shows that RoCPS1 is preferentially expressed in in trichomes from young leaves
brenda
additional information
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quantitative RT-PCR expression analysis on whole leaves shows that RoCPS1 is preferentially expressed in in trichomes from young leaves
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the enzyme sequence seems to contain a chloroplast transit peptide, but no other signal sequence or transmembrane domain
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
changing two adjacent residues that seem to serve as the catalytic base in the normal CPP synthase from Salvia miltiorrhiza (SmCPS) to the residues found in the closely related perigrinol diphosphate synthase from Marrubium vulgare (MvPPS), which produces a partially rearranged and hydroxylated product derived from the distinct syn stereoisomer of labdaenyl intermediate, alters the product outcome, cf. EC 5.5.1.14. Specifically, the relevant SmCPS:H315N/T316V double mutant produces terpentedienyl diphosphate, which is derived from complete substituent rearrangement of syn rather than normal labdaenyl intermediate. Alteration of the residues that normally serve as the catalytic base can impact stereocontrol
metabolism
physiological function
the chloroplastidic bifunctional diterpene synthase, isopimara-7,15-diene synthase (diTPS-ISO) from Picea abies and a cytosolic multifunctional cytochrome P450 (CYP720B4, UniProt ID E5FA70) from Picea sitchensis, which is associated to the endoplasmic reticulum. The diterpene synthase diTPS-ISO converts geranylgeranyl diphosphate (GGPP) to the tricyclic diterpene isopimara-7,15-diene (isopimaradiene)
additional information
evolution
the enzyme belongs to the class II diterpene synthases, phylogenetic tree, diterpene biosynthesis in gymnosperms, overview
evolution
the enzyme belongs to the class II diterpene synthases, phylogenetic tree, diterpene biosynthesis in gymnosperms, overview
evolution
diterpene synthases transcriptome analysis of Marrubium vulgare leaves, overview. CPS3 is a class II diterpene synthase, phylogenetic analysis
evolution
the bifunctional enzyme belongs to the class I and II diterpene synthases
metabolism
bifunctional class I/II PcLAS1 and PbLAS1 enzymes can supply (+)-copalyl diphosphate for the Monofunctional class I enzymes
metabolism
bifunctional diterpene cyclases are involved in hormone and defense compound biosyntheses in bryophytes and gymnosperms, respectively
metabolism
several stereoisomers of copalyl diphosphate (CDP) are found, among which the most common is ent-CDP, the precursor of gibberellins. Other isomers are syn-CDP and normal-CDP, the latter being utilized for the biosynthesis of diterpene resin acids in Gymnosperms and abietane-type tanshinones in Salvia miltiorrhiza. The second step of the cyclization is initiated through the formation of a carbocation upon ionization of the diphosphate linkage of CDP. This is catalyzed by class I terpene synthases which can transform CDP into a variety of polycyclic diterpenoids. By analogy to other labdane-type diterpenoids, the biosynthesis of the diterpene precursor of the carnosic acid pathway in rosemary proceeds in two sequential steps catalyzed by two distinct enzymes. The first is a class II TPS enzyme, CPS1, that yields normal CDP, which then is converted to miltiradiene by a KSL enzyme, miltiradiene synthase, EC 4.2.3.131, which apears in two isoforms, RoKSL1 and RoKSL2, in Rosmarinus officinalis. Hypothetical biosynthetic pathway of carnosic acid and carnosol produced in Rosmarinus officinalis, overview
metabolism
the bifunctional diterpene synthase, isopimara-7, 15-diene synthase (diTPS-ISO) and a multifunctional cytochrome P450, CYP720B4 perform the biosynthesis of isopimaric acid. The diterpene synthase converts geranylgeranyl diphosphate (GGPP) to the tricyclic diterpene isopimara-7,15-diene (isopimaradiene) via formation of (+)-copalyl diphosphate. In three subsequent oxygenation reactions, the endoplasmic reticulum-associated enzyme CYP720B4 catalyzes the conversion of isopimaradiene into isopimaric acid, pathway overview
additional information
enzyme structure by two-dimensional and three-dimensional NMR
additional information
-
enzyme structure by two-dimensional and three-dimensional NMR
additional information
class II diterpene cyclases (DTCs) utilize a general acid-base catalyzed cyclo-isomerization reaction to produce various stereoisomers of the eponymous labdaenyl carbocation intermediate, which can then undergo rearrangement and/or the addition of water prior to terminating deprotonation. Identification of the pair of residues that cooperatively serves as the catalytic base in the DTCs producing ent-copalyl diphosphate (CPP) required for gibberellin phytohormone biosynthesis in all vascular plants, overview
additional information
-
class II diterpene cyclases (DTCs) utilize a general acid-base catalyzed cyclo-isomerization reaction to produce various stereoisomers of the eponymous labdaenyl carbocation intermediate, which can then undergo rearrangement and/or the addition of water prior to terminating deprotonation. Identification of the pair of residues that cooperatively serves as the catalytic base in the DTCs producing ent-copalyl diphosphate (CPP) required for gibberellin phytohormone biosynthesis in all vascular plants, overview
additional information
enzyme CPS3 contains a DIDD functional motif
additional information
A0A0A7AN31
metabolomic profiling, and homology modeling and molecular docking
additional information
metabolomic profiling, and homology modeling and molecular docking
additional information
-
metabolomic profiling, and homology modeling and molecular docking
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UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). LAS_ABIBA
844
0
97273
Swiss-Prot
Mitochondrion (Reliability: 5)
TPS4_SELML
867
0
99915
Swiss-Prot
Chloroplast (Reliability: 2)
PDAC2_PHOAM
983
0
109972
Swiss-Prot
other Location (Reliability: 1)
CPS2_ISORU
419
0
48375
Swiss-Prot
other Location (Reliability: 2)
CPS3_MARVU
785
0
90197
Swiss-Prot
Chloroplast (Reliability: 5)
PADC1_PHOAM
1004
0
112836
Swiss-Prot
other Location (Reliability: 1)
PVCPS_TALVE
963
0
108180
Swiss-Prot
other Location (Reliability: 2)