Any feedback?
No. of entries
Information on EC 5.5.1.12 - copalyl diphosphate synthase
for references in articles please use BRENDA:EC5.5.1.12
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree 5 Isomerases
5.5 Intramolecular lyases
5.5.1 Intramolecular lyases (only sub-subclass identified to date)
5.5.1.12 copalyl diphosphate synthase
IUBMB 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.
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
- 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
-
abietane
-
labdane
- phaeosphaeria
-
norditerpenoids
- steviol
-
labdane-related
-
abietic
- synthesis
showSynonyms
copalyl diphosphate synthase, abietadiene synthase, smcps, smcps1, bifunctional diterpene cyclase, class ii diterpene synthase, class ii ditps, (+)-copalyl diphosphate synthase, rocps1, mvcps3, more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
(+)-copalyl diphosphate synthase
(+)-CPS
(-)-abietadiene synthase
-
-
-
-
abietadiene cyclase
-
-
-
-
abietadiene synthase
bifunctional LAS-type diTPS
class II diterpene synthase
class II diTPS
CPS1
CPS2
CPS3
cyclase, abietadiene
-
-
-
-
ISO
isopimaradiene synthase-type diTPS
LAS
levopimaradiene/abietadiene synthase-type diTPS
SmCPS1
SmCPS2
additional information
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
geranylgeranyl diphosphate = (+)-copalyl diphosphate
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
cyclization
-
bifunctional enzyme that catalyzes two sequential cyclization reactions in distinct active sites
intramolecular cyclization
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
MetaCyc
abietic acid biosynthesis, carnosate bioynthesis, dehydroabietic acid biosynthesis, isopimaric acid biosynthesis, levopimaric acid biosynthesis, neoabietic acid biosynthesis, palustric acid biosynthesis
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
157972-08-2
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate
copalyl diphosphate
-
Substrates: class II terpene synthase reaction
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
A0A0A7AN31, A0A0A7ANT1
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
A0A0A7AN31, A0A0A7ANT1
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: bifunctional enzyme that catalyzes two sequential cyclizations of geranylgeranyl diphosphate to isopimara-7,15-diene
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme shows substrate specificity, reaction product analysis by GC-MS. MvCPS3 does not produce ent-CPP, reaction of EC 5.5.1.13
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme shows substrate specificity, reaction product analysis by GC-MS. MvCPS3 does not produce ent-CPP, reaction of EC 5.5.1.13
Products: -
Products: -
?
additional information
?
-
Substrates: 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)
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
-
Substrates: 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
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
geranylgeranyl diphosphate
copalyl diphosphate
-
Substrates: class II terpene synthase reaction
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
?
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
-
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
A0A0A7AN31, A0A0A7ANT1
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
A0A0A7AN31, A0A0A7ANT1
Substrates: -
Products: -
Products: -
r
geranylgeranyl diphosphate
(+)-copalyl diphosphate
Substrates: -
Products: -
Products: -
r
additional information
?
-
Substrates: 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)
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
additional information
?
-
Substrates: 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
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
Mg2+
Mn2+
Mg2+
-
terpene synthases (TPS) require divalent metal ion co-factors, typically magnesium
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Tuberculosis
Crystal Structure and Mechanistic Molecular Modeling Studies of Mycobacterium tuberculosis Diterpene Cyclase Rv3377c.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
geranylgeranyl diphosphate
-
mutant T769A, value not determined
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
geranylgeranyl diphosphate
-
mutant T769A, value below 10000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda
contains 18 different amino acid sequence of copalyl diphosphate synthase, CPS
-
-
brenda
catalyzes the successive two-step type-B (protonation-initiated cyclization) and type-A (ionization-initiated cyclization) reactions of geranylgeranyl diphosphate (GGDP) producing successively (+)-copalyl diphosphate and miltiradiene, reactions of ECs 5.5.1.12 and 4.2.3.131, respectively
UniProt
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
quantitative RT-PCR expression analysis on whole leaves shows that RoCPS1 is preferentially expressed in in trichomes from young leaves
brenda
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Highest Expressing Human Cell Lines
Cell Line LinksPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
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 diterpene cyclases are involved in hormone and defense compound biosyntheses in bryophytes and gymnosperms, respectively
metabolism
bifunctional class I/II PcLAS1 and PbLAS1 enzymes can supply (+)-copalyl diphosphate for the Monofunctional class I enzymes
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
metabolism
pimar-15-en-8-yl+ is an intermediate in miltiradiene synthesis. At the beginning of the catalysis reaction, the class I active site utilizes a trinuclear metal cluster triggering the ionization of substrate (+)-copalyl diphosphate, resulting in the loss of diphosphate abstraction. The ionization of (+)-copalyl diphosphate leads to an allyl cation with two mesomeric structures. Then, the carbocation transfers to form the pimar-15-en-8-yl+. Subsequently, the specific C8-C9 double bond forms, with the participation of Y837, S717, H721 and E690. Both residues E690 and Y837 are located at the newly formed ring of miltiradiene and may participate in the final 1,2-methyl migration
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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). PVCPS_TALVE
963
0
108180
Swiss-Prot
Secretory Pathway (Reliability: 5)
CPS2_ISOJA
800
0
91179
Swiss-Prot
other Location (Reliability: 5)
CPS1_SALMI
793
0
90483
Swiss-Prot
other Location (Reliability: 3)
TPSD2_PINCO
850
0
97780
Swiss-Prot
other Location (Reliability: 1)
TPSD1_PINCO
857
0
98445
Swiss-Prot
other Location (Reliability: 2)
TPSD1_PINBN
857
0
98479
Swiss-Prot
other Location (Reliability: 2)
M4HXW7_PINCO
852
0
97893
TrEMBL
Mitochondrion (Reliability: 5)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
80000
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
-
secondary and tertiary structures of 18 different copalyl diphosphate synthases in Salvia miltiorrhiza. The main secondary structures are alpha-helix and random coil. Enzyme structure homology analysis
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
the enzyme sequence seems to contain a chloroplast transit peptide, but no other signal sequence or transmembrane domain
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structures of the apo-state and the GGPP-bound state reveal the presence of an internal channel for (+)-copalyl diphosphate produced in the class II active site moving towards the class I active site
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D404A
D621A
D625A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
D766A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
D845A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
E589A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
E699A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
E773A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
E778A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
N765A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
R584A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
R586A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
R762A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
S721A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
T617A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
T769A
T848A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
Y841F
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
H315N/T316V
site-directed mutagenesis, the 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
D391G/D392G
site-directed mutagenesis of DIDD motif residues, the mutant lacks type-B activity
D611G/D612G
site-directed mutagenesis of DDLMD motif residues, the mutant lacks type-A cyclase activity
E690C
mutant produces both sandaracopimaradiene and miltiradiene
E690G
mutant produces both sandaracopimaradiene and miltiradiene
E690H
mutant produces both sandaracopimaradiene and miltiradiene
E690N
mutant produces both sandaracopimaradiene and miltiradiene
E690Q
highest enzyme activity in all of the mutants examined
E690S
mutant exhibits partial enzyme activity and can convert GGPP to sandaracopimaradiene
E690T
mutant produces both sandaracopimaradiene and miltiradiene
Y837F
decrease in activity, mutant generates a mixture of sandaracopimaradiene, miltiradiene and two other products
additional information
T769A
-
no effect on geranylgeranyl diphosphate reaction, but lower turnover with copalyl diphosphate than wild-type
additional information
using a combination of protein and genetic engineering, significant improvements in the production of sclareol and several other isoprenoids is achieved, including cis-abienol, abietadiene, and beta-carotene. Recombinant expression of enzyme PaLAS in Saccharomyces cerevisiae AM94 cells, coexpression with different Saccharomyces cerevisiae farnesyl diphosphate synthase ERG20 variants increases diterpene yields by up to 15fold compared to expression of the Cistus creticus GGPPS
additional information
transient heterologous expression of the isopimaric acid pathway in Nicotiana benthamiana. Expressing DXS and GGPPs from Plectranthus barbatus in Nicotiana benthamiana are efficient in boosting diterpenoid levels compared to coexpression of the Nicotiana endogenous DXS and GGPPs genes, which have no effect on boosting diterpenoid level. Pigment analysis of infiltrated leaves, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme by nickel affinity chromatography from Escherichia coli strains Tuner (DE3) or Origami B (DE3)
A0A0A7AN31, A0A0A7ANT1
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis of 18 different amino acid sequence of copalyl diphosphate synthase, CPS, phylogenetic analysis and tree
-
expression in Escherichia coli
expression of His-tagged enzyme in Escherichia coli
functional expression of Picea abies isopimara-7,15-diene synthase (diTPS-ISO) in Nicotiana benthamiana leaves via Agrobacterium tumefaciens transfection method, coexpression with a multifunctional cytochrome P450 (CYP720B4) from Picea sitchensis, subcloning in Escherichia coli strain NEB10beta
gene CPS1, phylogenetic analysis and tree, functional recombinant expression in Saccharomyces cerevisiae strain AM113, with co-overexpressing of GGDPS1 from Cistus creticus, and Nicotiana benthamiana, heterologous expression of the RoCPS1 protein in Escherichia coli fails
gene CPS3, phylogenetic analysis and tree, quantitative expression analysis, functional expression of MvCPS3 alone or with MvELS (multifunctional betaalpha-domain class I diterpene synthase) or MvEKS (ent-kaurene synthase) in engineered Nicotiana benthamiana
gene SmCPS1, phylogenetic analysis, a 289-bp gene-specific sequence including the 3' UTR of SmCPS1 is amplified by PCR using cDNA as a template and then cloned into the pK7GWIWG (II) binary, then introduced into Agrobacterium tumefaciens strain EHA105 by electroporation for ransformation of leaf explants from Salvia miltiorrhiza bh2-7 plants, recombinant expression of His-tagged enzyme in Escherichia coli strains Tuner (DE3) or Origami B (DE3)
A0A0A7AN31, A0A0A7ANT1
gene SmCPS2, phylogenetic analysis, recombinant expression of His-tagged enzyme in Escherichia coli strains Tuner (DE3) or Origami B (DE3)
A0A0A7AN31, A0A0A7ANT1
gene TPS-LAS, recombinant expression in Saccharomyces cerevisiae strain AM94, a yeast strain engineered for the production of isoprenoids, which contains three chromosomally integrated copies of a degradation stabilized variant of HMG2 and a heterozygous deletion of ERG9, and in strain AM204, each with or without coexpression of yeast protein Erg20p(F96C), a yeast FPP synthase, overview
Site-directed mutagenesis is carried out via PCR amplification with overlapping mutagenic primers, and the mutant genes verify by complete sequencing. The resulting wild type and mutant genes are then transferred via directional recombination to the T7-promoter and N-terminal 6xhis fusion expression vector pDEST17. Use of the pDEST17 vector results in a 25 amino acid residue linker between the 6 His-tag and the cloned protein.
-
expression in Escherichia coli
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
synthesis
the development of yeast strains carrying the engineered Erg20p, which support efficient isoprenoid production, e.g. by abietadiene synthase, and can be used as a dedicated chassis for diterpene production or biosynthetic pathway elucidation. The design developed can be applied to the production of any GGPP-derived isoprenoid and is compatible with other yeast terpene production platforms, method overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
LeFever, R.E.; Vogel, B.S.; Croteau, R.
Diterpenoid resin acid biosynthesis in conifers: enzymic cyclization of geranylgeranyl pyrophosphate to abietadiene, the precursor of abietic acid
Arch. Biochem. Biophys.
313
139-149
1994
Abies grandis, Pinus contorta
brenda
Ravn, M.M.; Coates, R.M.; Jetter, R.; Croteau, R.B.
Stereospecific intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to (-)-abietadiene catalyzed by recombinant cyclase from grand fir (Abies grandis)
Chem. Commun. (Camb.)
1998
21-22
1998
Abies grandis, Pinus contorta
-
brenda
Ravn, M.M.; Coates, R.M.; Flory, J.E.; Peters, R.J.; Croteau, R.
Stereochemistry of the cyclization-rearrangement of (+)-copalyl diphosphate to (-)-abietadiene catalyzed by recombinant abietadiene synthase from Abies grandis
Org. Lett.
2
573-576
2000
Abies grandis
brenda
Peters, R.J.; Flory, J.E.; Jetter, R.; Ravn, M.M.; Lee, H.J.; Coates, R.M.; Croteau, R.B.
Abietadiene synthase from grand fir (Abies grandis): characterization and mechanism of action of the "pseudomature" recombinant enzyme
Biochemistry
39
15592-15602
2000
Abies grandis
brenda
Peters, R.J.; Ravn, M.M.; Coates, R.M.; Croteau, R.B.
Bifunctional abietadiene synthase: Free diffusive transfer of the (+)-copalyl diphosphate intermediate between two distinct active sites
J. Am. Chem. Soc.
123
8974-8978
2001
Abies grandis
brenda
Peters, R.J.; Croteau, R.B.
Abietadiene synthase catalysis: conserved residues involved in protonation-initiated cyclization of geranylgeranyl diphosphate to (+)-copalyl diphosphate
Biochemistry
41
1836-1842
2002
Abies grandis
brenda
Peters, R.J.; Croteau, R.B.
Abietadiene synthase catalysis: mutational analysis of a prenyl diphosphate ionization-initiated cyclization and rearrangement
Proc. Natl. Acad. Sci. USA
99
580-584
2002
Abies grandis
brenda
Ravn, M.M.; Peters, R.J.; Coates, R.M.; Croteau, R.
Mechanism of abietadiene synthase catalysis: stereochemistry and stabilization of the cryptic pimarenyl carbocation intermediates
J. Am. Chem. Soc.
124
6998-7006
2002
Abies grandis
brenda
Peters, R.J.; Carter, O.A.; Zhang, Y.; Matthews, B.W.; Croteau, R.B.
Bifunctional abietadiene synthase: mutual structural dependence of the active sites for protonation-initiated and ionization-initiated cyclizations
Biochemistry
42
2700-2707
2003
Abies grandis
brenda
Smith, M.W.; Yamaguchi, S.; Ait-Ali, T.; Kamiya, Y.
The first step of gibberellin biosynthesis in pumpkin is catalyzed by at least two copalyl diphosphate synthases encoded by differentially regulated genes
Plant Physiol.
118
1411-1419
1998
Cucurbita maxima
brenda
Tudzynski, B.; Kawaide, H.; Kamiya, Y.
Gibberellin biosynthesis in Gibberella fujikuroi: cloning and characterization of the copalyl diphosphate synthase gene
Curr. Genet.
34
234-240
1998
Fusarium fujikuroi
brenda
Zhou, K.; Peters, R.J.
Investigating the conservation pattern of a putative second terpene synthase divalent metal binding motif in plants
Phytochemistry
70
366-369
2009
Abies grandis
brenda
Sugai, Y.; Ueno, Y.; Hayashi, K.; Oogami, S.; Toyomasu, T.; Matsumoto, S.; Natsume, M.; Nozaki, H.; Kawaide, H.
Enzymatic (13)C labeling and multidimensional NMR analysis of miltiradiene synthesized by bifunctional diterpene cyclase in Selaginella moellendorffii
J. Biol. Chem.
286
42840-42847
2011
Selaginella moellendorffii (G9MAN7), Selaginella moellendorffii
brenda
Zerbe, P.; Chiang, A.; Yuen, M.; Hamberger, B.; Hamberger, B.; Draper, J.A.; Britton, R.; Bohlmann, J.
Bifunctional cis-abienol synthase from Abies balsamea discovered by transcriptome sequencing and its implications for diterpenoid fragrance production
J. Biol. Chem.
287
12121-12131
2012
Abies balsamea (H8ZM71)
brenda
Hall, D.; Zerbe, P.; Jancsik, S.; Quesada, A.; Dullat, H.; Madilao, L.; Yuen, M.; Bohlmann, J.
Evolution of conifer diterpene synthases: diterpene resin acid biosynthesis in lodgepole pine and jack pine involves monofunctional and bifunctional diterpene synthases
Plant Physiol.
161
600-616
2013
Pinus banksiana (M4HXU6), Pinus contorta (M4HXW7)
brenda
Brueckner, K.; Bozic, D.; Manzano, D.; Papaefthimiou, D.; Pateraki, I.; Scheler, U.; Ferrer, A.; de Vos, R.C.; Kanellis, A.K.; Tissier, A.
Characterization of two genes for the biosynthesis of abietane-type diterpenes in rosemary (Rosmarinus officinalis) glandular trichomes
Phytochemistry
101
52-64
2014
Salvia rosmarinus (W8QQT6), Salvia rosmarinus
brenda
Zerbe, P.; Chiang, A.; Dullat, H.; ONeil-Johnson, M.; Starks, C.; Hamberger, B.; Bohlmann, J.
Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare
Plant J.
79
914-927
2014
Marrubium vulgare (A0A075FA51), Marrubium vulgare
brenda
Cui, G.; Duan, L.; Jin, B.; Qian, J.; Xue, Z.; Shen, G.; Snyder, J.H.; Song, J.; Chen, S.; Huang, L.; Peters, R.J.; Qi, X.
Functional divergence of diterpene syntheses in the medicinal plant Salvia miltiorrhiza
Plant Physiol.
169
1607-1618
2015
Salvia miltiorrhiza f. alba (A0A0A7AN31), Salvia miltiorrhiza f. alba (A0A0A7ANT1), Salvia miltiorrhiza f. alba bh2-7 (A0A0A7AN31), Salvia miltiorrhiza f. alba bh2-7 (A0A0A7ANT1)
brenda
Schulte, S.; Potter, K.C.; Lemke, C.; Peters, R.J.
Catalytic bases and stereocontrol in Lamiaceae class II diterpene cyclases
Biochemistry
57
3473-3479
2018
Salvia miltiorrhiza (B8PQ84), Salvia miltiorrhiza
brenda
Li, Q.; Di, P.; Lu, W.; Zhang, L.; Chen, W.
Bioinformatics analysis of copalyl diphosphate synthase in Salviae Miltiorrhizae Radix et Rhizoma
Chin. Tradit. Herbal Drugs
46
887-894
2015
Salvia miltiorrhiza
-
brenda
Gnanasekaran, T.; Vavitsas, K.; Andersen-Ranberg, J.; Nielsen, A.Z.; Olsen, C.E.; Hamberger, B.; Jensen, P.E.
Heterologous expression of the isopimaric acid pathway in Nicotiana benthamiana and the effect of N-terminal modifications of the involved cytochrome P450 enzyme
J. Biol. Eng.
9
24
2015
Picea abies (Q675L5)
brenda
Ignea, C.; Trikka, F.; Nikolaidis, A.; Georgantea, P.; Ioannou, E.; Loupassaki, S.; Kefalas, P.; Kanellis, A.; Roussis, V.; Makris, A.; Kampranis, S.
Efficient diterpene production in yeast by engineering Erg20p into a geranylgeranyl diphosphate synthase
Metab. Eng.
27
65-75
2015
Picea abies (Q675L4)
-
brenda
Murphy, K.M.; Ma, L.T.; Ding, Y.; Schmelz, E.A.; Zerbe, P.
Functional characterization of two class II diterpene synthases indicates additional specialized diterpenoid pathways in maize (Zea mays)
Front. Plant Sci.
9
1542
2018
Zea mays
brenda
Tong, Y.; Ma, X.; Hu, T.; Chen, K.; Cui, G.; Su, P.; Xu, H.; Gao, W.; Jiang, T.; Huang, L.
Structural and mechanistic insights into the precise product synthesis by a bifunctional miltiradiene synthase
Plant Biotechnol. J.
21
165-175
2023
Selaginella moellendorffii (G9MAN7)
brenda
Yang, R.; Du, Z.; Qiu, T.; Sun, J.; Shen, Y.; Huang, L.
Discovery and functional characterization of a diverse diterpene synthase family in the medicinal herb Isodon lophanthoides var. gerardiana
Plant Cell Physiol.
62
1423-1435
2021
Isodon lophanthoides var. gerardianus
brenda
Ma, L.T.; Wang, C.H.; Hon, C.Y.; Lee, Y.R.; Chu, F.H.
Discovery and characterization of diterpene synthases in Chamaecyparis formosensis Matsum. which participated in an unprecedented diterpenoid biosynthesis route in conifer
Plant Sci.
304
110790
2021
Chamaecyparis formosensis
brenda
EXTERNAL LINKS (specific for EC-Number 5.5.1.12)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2026.1 (March 2026)
About BRENDA
Social media
Help
Survey
Download
Contribution
Legal
Curated at
Member of
![DSMZ Digital Diversity]()
![Global Core Biodata Resource]()
![ELIXIR Core Data Resource]()
![German Network for Bioinformatics Infrastructure]()
