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Information on EC 4.2.3.44 - isopimara-7,15-diene synthase
for references in articles please use BRENDA:EC4.2.3.44
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EC Tree 4 Lyases
4.2 Carbon-oxygen lyases
4.2.3 Acting on phosphates
4.2.3.44 isopimara-7,15-diene synthase
IUBMB Comments
The enzyme only gave isopimara-7,15-diene.
The enzyme appears in viruses and cellular organisms
showSynonyms
isopimara-7,15-diene synthase, irksl6, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PaTPS-Iso
additional information
PaTPS-Iso
-
-
-
-
additional information
see also EC 4.2.3.183
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(+)-copalyl diphosphate = isopimara-7,15-diene + diphosphate
-
-
-
-
(+)-copalyl diphosphate = isopimara-7,15-diene + diphosphate
proposed reaction scheme
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PATHWAY SOURCE
PATHWAYS
MetaCyc
isopimaric acid biosynthesis
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SYSTEMATIC NAME
IUBMB Comments
copalyl diphosphate-lyase (isopimara-7,15-diene-forming)
The enzyme only gave isopimara-7,15-diene.
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: proposed reaction scheme
Products: -
Products: -
?
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
additional information
?
-
Substrates: diterpene profiling of plant tissues (root periderms, root cortexes and xylems, stems and leaves) and compound identification by GC-MS analysis
Products: -
Products: -
-
additional information
?
-
Substrates: GC-MS analysis of compounds
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 (cf. EC 5.5.1.12) and the formation of isopimara-7,15-diene from (+)-copalyl diphosphate. Compound identification and quantification by GC-MS analysis
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
(+)-copalyl diphosphate
isopimara-7,15-diene + diphosphate
Substrates: -
Products: -
Products: -
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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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
plants are collected from the Yaowang Mountain in Guangzhou University of Chinese Medicine (113°E, 23°N) on April 2019
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
ent-isopimara-7,15-diene synthase AaKSL1 is widely expressed in leaves, stems, and roots. Ent-isopimara-7,15-diene accumulates in both leaves and roots, metabolite analysis
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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
the Ile and Val mutants with relatively large aliphatic side chains may change the substrate conformation and shield the carbocation of the pimar-15-en-8-yl+ intermediate, thus preventing the addition of a water molecule. By contrast, Ala and other small and/or hydrophilic residues, e.g. Ser and Thr may allow the contact between the pimar-15-en-8-yl+ intermediate and a water molecule, leading to the carbocation neutralization through the addition of a water molecule to form nezukol. In addition, mutation of IrTPS Ala 523 that corresponds to IlKSL5 A513 to Ile shows the same effect by altering product from nezukol to isopimar-7,15-diene
metabolism
physiological function
additional information
the hydrophobicity and the size of amino acid 513 play an important role in determining the addition of water by IlKSL5. To identify the amino acid residue controlling the water addition of enzyme IlKSL5, homology-based structure models of IlKSL5 are created using the crystal structure of abietadiene synthase from Abies grandis (PDB ID 3S9V) as template
evolution
IrKSL3 and IrKSL6 have the gammabetaalpha tridomain structure, as these proteins tend to possess the bidomain structure of IrKSL1, highlighting the evolutionary history of KSL gene domain loss and further elucidating chemical diversity evolution from a macroevolutionary stance in Lamiaceae. Identified IrCPS4 is predicted to be involved in oridonin biosynthesis, three KSL genes are involved in ent-CPP interactions, and a normal-CPP mediated miltiradiene and isopimaradiene biosynthesis pathway. The three KSL genes bearing different domain structures are involved in the normal-CPP mediated biosynthesis. The tridomain enzymes (IrKSL3 and IrKSL6) belong to an ancestral KSL clade that has the loss of g domain, a widespread occurrence in the Lamiaceae. Evolutionary origin of the gamma-domain loss
evolution
the enzyme belongs to the class I diterpene synthases (DiTPSs). Phylogenetic tree, joining trees of Isodon lophanthoides diTPSs with known class II and class I enzymes based on aligned protein sequences, overview. IlKSL5 belongs to a sub-clade involved in specialized metabolism
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
ent-kaurene diterpenoids are the largest group of known Isodon diterpenoids, five copalyl diphosphate synthase (CPS) and six kaurene synthase-like (KSL) genes are identified by transcriptome profiling of Isodon rubescens leaves. IrKSL6 reacts with normal-CP, synthesized by (+)-copalyl diphosphate synthases IrCPS1 or IrCPS2 (EC 5.5.1.12) to produce isopimaradiene. Enzyme IrKSL2 generates a product with identical EI mass spectrum to isopimaradiene (isopimara-7,15-diene), from ent-copalyl diphosphate
metabolism
biosynthetic pathway of specialized and general metabolism of diterpenoids in medicinal plant Isodon lophanthoides var. gerardiana, overview. Diverse diTPSs producing distinct diterpene scaffolds form the foundation of the diterpene chemical diversity. Diterpene scaffolds are further modified by P450s and other modification enzymes
metabolism
a complex repertoire of diterpenoids is found in Artemisia annua with important roles in glandular trichome (GT) formation, artemisinin accumulation and stress resilience. Metabolic engineering of diterpenoids simultaneously increases the artemisinin yield and stress resistance. Transcriptome and metabolic profiling suggests that bioactive gibberellins (GAs) GA4/GA1 promote GT formation. Protein-protein interactions (PPIs) between AaKSL1 and AaCPS2 in the plastids highlighted their potential functions in modulating metabolic flux to gibberellins (GAs) or ent-isopimara-7,15-diene-derived metabolites (IDMs) through metabolic engineering
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 also converts geranylgeranyl diphosphate (GGPP) to the tricyclic diterpene isopimara-7,15-diene (isopimaradiene)
physiological function
enzymes from diTPS class II and class I, AaCPS2 and AaKSL1, respectively, interact and function in specialized diterpenoid metabolism as a defense against stress. AaKSL1 converts ent-copalyl diphosphate (ent-CPP) into ent-isopimara-7,15-diene. Simultaneous overexpression of AaCPS2 and AaKSL1 may increase gibberellic acid and ent-isopimara-7,15-diene-derived metabolite (IDM) biosynthesis at the same time. Antifungal activity of ent-isopimara-7,15-diene-derived metabolites against Fusarium oxysporum
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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). MISO1_PINCO
876
0
100687
Swiss-Prot
other Location (Reliability: 2)
A0A8F6T6B3_9LAMI
771
0
88076
TrEMBL
-
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A513I
site-directed mutagenesis, substitution of A513 with Ile completely alters the product from nezukol to isopimara-7,15-diene
A513S
site-directed mutagenesis, mutant IlKSL5A513S mutant predominantly produces nezukol, like the wild-type enzyme
A513T
site-directed mutagenesis, mutant IlKSL5A513T produces a mixture of nezukol and isopimara-7,15-diene
A513V
site-directed mutagenesis, mutant IlKSL5A513V produces predominantly isopimar-7,15-diene with trace amount of nezukol
additional information
additional information
the hydrophobicity and the size of amino acid 513 play an important role in determining the addition of water by IlKSL5. The Ile and Val mutants with relatively large aliphatic side chains may change the substrate conformation and shield the carbocation of the pimar-15-en-8-yl+ intermediate, thus preventing the addition of a water molecule. By contrast, Ala and other small and/or hydrophilic residues, e.g. Ser and Thr may allow the contact between the pimar-15-en-8-yl+ intermediate and a water molecule, leading to the carbocation neutralization through the addition of a water molecule to form nezukol. In addition, mutation of IrTPS Ala 523 that corresponds to IlKSL5 A513 to Ile shows the same effect by altering product form nezukol to isopimar-7,15-diene. Product comparison with the parallel product of a monofunctional isopimara-7,15-diene synthase from Pinus contorta (PcmISO1)
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
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged KSL6 from Escherichia coli strain Tuner(DE3) by nickel affinity chromatography
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, phylogenetic analysis, recombinant expression of wild-type and mutant enzymes in Saccharomyces cerevisiae strain YS100, subcloning in Escherichia coli strain TOP10, transient heterologous expression of wild-type and mutant enzymes in Nicotiana benthaminana via transfection with Agrobacterium tumefaciens strain LBA4404, quantitative RT-PCR enzyme expression analysis
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 KSL6, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic analysis, recombinant expression of His-tagged codon-optimized KSL6 in Escherichia coli strain Tuner(DE3)
transient heterologous expression of the enzyme in Nicotiana benthaminana via transfection with Agrobacterium strain GV3101 quantitative real-time PCR enzyme expression analysis
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Martin, D.M.; Faeldt, J.; Bohlmann, J.
Functional characterization of nine Norway spruce TPS genes and evolution of gymnosperm terpene synthases of the TPS-d subfamily
Plant Physiol.
135
1908-1927
2004
Picea abies (Q675L5), Picea abies
brenda
Jin, B.; Cui, G.; Guo, J.; Tang, J.; Duan, L.; Lin, H.; Shen, Y.; Chen, T.; Zhang, H.; Huang, L.
Functional diversification of kaurene synthase-like genes in Isodon rubescens
Plant Physiol.
174
943-955
2017
Isodon rubescens (A0A1Z3GCD1)
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
Chen, R.; Bu, Y.; Ren, J.; Pelot, K.; Hu, X.; Diao, Y.; Chen, W.; Zerbe, P.; Zhang, L.
Discovery and modulation of diterpenoid metabolism improves glandular trichome formation, artemisinin production and stress resilience in Artemisia annua
New Phytol.
230
2387-2403
2021
Artemisia annua (A0A8B0RHM8)
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 (A0A8F6T6B3)
brenda
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