Information on EC 4.2.3.108 - 1,8-cineole synthase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
4.2.3.108
-
RECOMMENDED NAME
GeneOntology No.
1,8-cineole synthase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
geranyl diphosphate + H2O = 1,8-cineole + diphosphate
show the reaction diagram
-
-
-
-
geranyl diphosphate + H2O = 1,8-cineole + diphosphate
show the reaction diagram
substrate in left-hynded screw-sense orientation isomerizes to (3R)-linalyl diphosphate which in anti,endo-conformation cyclizes to the (4R)-alpha-terpinyl intermediate and thence to cineole following the addition of water
-
geranyl diphosphate + H2O = 1,8-cineole + diphosphate
show the reaction diagram
syn-stereochemistry for both C-O-bond-forming steps. Reaction starts with allylic rearrangement of geranyl diphosphate to (R)-linalyl diphosphate, followed by SN' cyclization to alpha-terpineol and proton-induced cyclization of the C=C-double bond and the tertiary hydroxyl groups
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Biosynthesis of secondary metabolites
-
-
Metabolic pathways
-
-
monoterpene biosynthesis
-
-
Monoterpenoid biosynthesis
-
-
SYSTEMATIC NAME
IUBMB Comments
geranyl-diphosphate diphosphate-lyase (cyclizing, 1,8-cineole-forming)
Requires Mn2+ or Zn2+. Mg2+ is less effective than either. 1,8-Cineole is the main product from the enzyme with just traces of other monoterpenoids. The oxygen atom is derived from water. The reaction proceeds via linalyl diphosphate and alpha-terpineol, the stereochemistry of both depends on the organism. However neither intermediate can substitute for geranyl diphosphate. The reaction in Salvia officinalis (sage) proceeds via (-)-(3R)-linalyl diphosphate [1-3] while that in Arabidopsis (rock cress) proceeds via (+)-(3S)-linalyl diphosphate [4].
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
1,8-cineole cyclase; geranyl pyrophoshate:1,8-cineole cyclase
-
-
-
-
1,8-cineole synthetase
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
110637-19-9
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
parents Lavandula angustifolia and Lavandula latifolia
UniProt
Manually annotated by BRENDA team
Streptomyces clavuligerus DSM 738
-
UniProt
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(3R)-linalyl diphosphate + H2O
? + diphosphate
show the reaction diagram
-
-
-
-
?
(3S)-linalyl diphosphate + H2O
? + diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate
1,8-cineole + diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate
1,8-cineole + diphosphate
show the reaction diagram
O81193
-
-
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
P0DI76
-
52% 1,8-cineole plus 0.6% (+)-alpha-thujene, 1.9% (2)-(1S)-alpha-pinene, 14.5% (-)-sabinene, 7.8% (2)-(1S)-beta-pinene, 13.3% myrcene, 4.0% (2)-(4S)-limonene, (E)-2.7% beta-ocimene, 0.8% terpinolene, and 2.4% alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
A6XH05
-
72.4% 1,8-cineole, 7.1% alpha-terpineol, 9.1% beta-pinene, 4.6% alpha-pinene, 3.6% sabinene, 2.2% myrcene, and <1% limonene
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
O81191
-
79% 1,8-cineole plus 20% of a mixture of (+)- and (-)-alpha-pinene, (+)- and (-)-beta-pinene, myrcene and (+)-sabinene
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
I3WEV8
-
80% 1,8-cineole plus 7.9% sabinene, 6.6% alpha-phellandrene, 2.3% limonene, and 1.7% alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
A5Y5L5
-
major product is 1,8-cineole plus limonene, sabinene, E-beta-ocimene, b-myrcene, alpha-pinene, and alpha-terpineole
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
H2ELN1
-
products are sabinene, beta-myrcene, limonene, 1,8-cineole, and 36% alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
H6WZF2
-
products are sabinene, beta-myrcene, limonene, 1,8-cineole, and 41% alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
-
-
water is the sole source of the ether oxygen atom of 1,8-cineole
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
B5GMG2
-
1,8-cineole is the single major product
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
I7C6Y2
-
products are alpha-pinene, beta-pinene, sabinene, beta-myrcene, limonene, 1,8-cineole and alpha-terpineol. 1,8-Cineole and alpha-terpineol are the major products, enzyme synthesizes 2- to 3fold more cineol than alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
I7CTV3
-
products are alpha-pinene, beta-pinene, sabinene, beta-myrcene, limonene, 1,8-cineole and alpha-terpineol. 1,8-Cineole and alpha-terpineol are the major products, enzyme synthesizes 2- to 3fold more cineol than alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
I7D3D7
-
products are alpha-pinene, beta-pinene, sabinene, beta-myrcene, limonene, 1,8-cineole and alpha-terpineol. 1,8-Cineole and alpha-terpineol are the major products, enzyme synthesizes 2- to 3fold more cineol than alpha-terpineol
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
W8GLB1
-
products are alpha-pinene, beta-pinene, sabinene, beta-myrcene, limonene, 1,8-cineole and alpha-terpineol. 1,8-cineole is the major compound comprising ca. 50% of the products. alpha-Terpineol contributes approximately 25%
-
?
neryl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
I3WEV8
-
61% 1,8-cineole plus 18.5% sabinene, 8% alpha-phellandrene, 3.3% limonene, and 5.5% alpha-terpineol
-
?
neryl diphosphate + H2O
? + diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate + H2O
1,8-cineole + diphosphate
show the reaction diagram
Streptomyces clavuligerus DSM 738
B5GMG2
-
1,8-cineole is the single major product
-
?
additional information
?
-
-
no substrate: farnesyl diphosphate
-
-
-
additional information
?
-
P0DI76
no substrate: farnesyl diphosphate
-
-
-
additional information
?
-
B5GMG2
no substrate: farnesyl diphosphate
-
-
-
additional information
?
-
W8GLB1
enzyme is a multi product enzyme synthesizing simultaneously the seven monoterpenes of the cineole cassette
-
-
-
additional information
?
-
I7C6Y2
enzyme is a multi product enzyme synthesizing simultaneously the seven monoterpenes of the cineole cassette
-
-
-
additional information
?
-
I7CTV3
enzyme is a multi product enzyme synthesizing simultaneously the seven monoterpenes of the cineole cassette
-
-
-
additional information
?
-
I7D3D7
enzyme is a multi product enzyme synthesizing simultaneously the seven monoterpenes of the cineole cassette
-
-
-
additional information
?
-
Streptomyces clavuligerus DSM 738
B5GMG2
no substrate: farnesyl diphosphate
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
-
or Mn2+, absolutely required. Km value 5 mM
Mg2+
A5Y5L5
or Mn2+, required. Mg2+ is preferred over Mn2+
Mg2+
P0DI76
or Mn2+, absolutely required. Fully active at 40 mM
Mn2+
-
or Mg2+, absolutely required. Km value 0.3 mM
Mn2+
A5Y5L5
or Mg2+, required. Mn2+ is preferred over Mn2+
Mn2+
P0DI76
or Mg2+, absolutely required. Fully active at 1 mM
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-Fluorogeranyl diphosphate
-
competitive
2-Fluorolinalyl diphosphate
-
competitive
4-hydroxymercuribenzoate
-
inhibition is reversed by presence of cysteine
benzyl bromide
-
-
diethyl dicarbonate
-
inhibition is reversed by presence of hydroxylamine
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
H6WZF2
enzyme activity reaches its maximum at the second day after anthesis when flowers are fully opened. Enzyme activity is highest at the transition from day to night, diurnal rhythm
-
additional information
H2ELN1
enzyme activity reaches its maximum at the second day after anthesis when flowers are fully opened. Enzyme activity is highest at the transition from day to night, diurnal rhythm
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.002
(3R)-linalyl diphosphate
-
pH 6.3, 30C
0.0042
(3S)-linalyl diphosphate
-
pH 6.3, 30C
0.00017
geranyl diphosphate
B5GMG2
pH 8.0, 30C
0.0002
geranyl diphosphate
P0DI76
temperature not specified in the publication, pH not specified in the publication
0.0011
geranyl diphosphate
-
pH 6.3, 30C
0.0057
geranyl diphosphate
I3WEV8
pH 7.0, 30C
0.007
geranyl diphosphate
-
pH 7.1, 31C
0.0119
geranyl diphosphate
A6XH05
mutant N338A, pH 7.0, 22C
0.0129
geranyl diphosphate
A6XH05
mutant N338I/A339T/G447S/I449P/P450T, pH 7.0, 22C
0.0144
geranyl diphosphate
A6XH05
mutant N338S, pH 7.0, 22C
0.0265
geranyl diphosphate
A6XH05
mutant N338L, pH 7.0, 22C
0.055
geranyl diphosphate
A6XH05
mutant N338V, pH 7.0, 22C
0.0566
geranyl diphosphate
A6XH05
mutant N338I, pH 7.0, 22C
0.0654
geranyl diphosphate
A6XH05
wild-type, pH 7.0, 22C
0.0955
geranyl diphosphate
A6XH05
mutant N338I/A339T/G447S, pH 7.0, 22C
0.136
geranyl diphosphate
A6XH05
mutant N338I/A339T, pH 7.0, 22C
0.201
geranyl diphosphate
A6XH05
mutant N338C, pH 7.0, 22C
0.0045
neryl diphosphate
-
pH 6.3, 30C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.001
geranyl diphosphate
P0DI76
temperature not specified in the publication, pH not specified in the publication
0.0043
geranyl diphosphate
A6XH05
mutant N338I/A339T/G447S/I449P/P450T, pH 7.0, 22C; mutant N338I/A339T/G447S, pH 7.0, 22C
0.0088
geranyl diphosphate
I3WEV8
pH 7.0, 30C
0.009
geranyl diphosphate
A6XH05
mutant N338L, pH 7.0, 22C
0.012
geranyl diphosphate
A6XH05
mutant N338V, pH 7.0, 22C
0.022
geranyl diphosphate
A6XH05
mutant N338S, pH 7.0, 22C
0.024
geranyl diphosphate
A6XH05
mutant N338I/A339T, pH 7.0, 22C
0.052
geranyl diphosphate
A6XH05
mutant N338C, pH 7.0, 22C
0.053
geranyl diphosphate
A6XH05
wild-type, pH 7.0, 22C
0.069
geranyl diphosphate
A6XH05
mutant N338A, pH 7.0, 22C
0.079
geranyl diphosphate
B5GMG2
pH 8.0, 30C
0.096
geranyl diphosphate
A6XH05
mutant N338I, pH 7.0, 22C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.045
geranyl diphosphate
A6XH05
mutant N338I/A339T/G447S, pH 7.0, 22C
175
0.177
geranyl diphosphate
A6XH05
mutant N338I/A339T, pH 7.0, 22C
175
0.22
geranyl diphosphate
A6XH05
mutant N338V, pH 7.0, 22C
175
0.26
geranyl diphosphate
A6XH05
mutant N338C, pH 7.0, 22C
175
0.33
geranyl diphosphate
A6XH05
mutant N338I/A339T/G447S/I449P/P450T, pH 7.0, 22C
175
0.34
geranyl diphosphate
A6XH05
mutant N338L, pH 7.0, 22C
175
0.81
geranyl diphosphate
A6XH05
wild-type, pH 7.0, 22C
175
1.53
geranyl diphosphate
A6XH05
mutant N338S, pH 7.0, 22C
175
1.69
geranyl diphosphate
A6XH05
mutant N338I, pH 7.0, 22C
175
5.79
geranyl diphosphate
A6XH05
mutant N338A, pH 7.0, 22C
175
460
geranyl diphosphate
B5GMG2
pH 8.0, 30C
175
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0032
2-Fluorogeranyl diphosphate
-
pH 6.3, 30C
0.0048
2-Fluorolinalyl diphosphate
-
pH 6.3, 30C
0.005
4-hydroxymercuribenzoate
-
pH 6.3, 30C
0.85
benzyl bromide
-
pH 6.3, 30C
0.3
diethyl dicarbonate
-
pH 6.3, 30C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.6
-
isoelectric focusing
5.8
-
calculated
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
epidermal gland of leaf
Manually annotated by BRENDA team
P0DI76
promoter activity is primarily found in the epidermis, cortex, and stele of mature primary and lateral roots, but not in the root meristem or the elongation zone
Manually annotated by BRENDA team
H6WZF2
pistil
Manually annotated by BRENDA team
-
gene expression of monoterpene synthases and actual monoterpene formation is highest in young leaf
Manually annotated by BRENDA team
O81193
sabinene synthase transcripts show the highest monoterpene synthase transcript expression, about an order of magnitude higher than cineole synthase and borneol synthase
Manually annotated by BRENDA team
H6WZF2
adaxial and abaxial epidermis of petals
Manually annotated by BRENDA team
H2ELN1
adaxial and abaxial epidermis of petals. 1,8-cineole is the major compound emitted
Manually annotated by BRENDA team
A5Y5L5
only expressed in sigma/style tissue and in petals
Manually annotated by BRENDA team
P0DI76
promoter activity is primarily found in the epidermis, cortex, and stele of mature primary and lateral roots, but not in the root meristem or the elongation zone
Manually annotated by BRENDA team
P0DI76
promoter activity is primarily found in the epidermis, cortex, and stele of mature primary and lateral roots, but not in the root meristem or the elongation zone
Manually annotated by BRENDA team
A5Y5L5
only expressed in sigma/style tissue and in petals
Manually annotated by BRENDA team
A5Y5L5
only expressed in sigma/style tissue and in petals
Manually annotated by BRENDA team
-
glandular trichome
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
60000
-
gel filtration
717147
72000
-
gel filtration
3779
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
P0DI76
x * 60000, SDS-PAGE
?
B5GMG2
x * 40000, SDS-PAGE
?
I3WEV8
x * 63000, SDS-PAGE, x * 68500, calculated
?
A5Y5L5
x * 64550, calculated
?
Streptomyces clavuligerus DSM 738
-
x * 40000, SDS-PAGE
-
monomer
-
x * 69400, calculated
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
sequence contains a putative chloroplast targeting peptide
proteolytic modification
I3WEV8
the N-terminal 52 amino acids are predicted to code for a transit peptide
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
homology-based protein model constructed on the 3-D crystal structure of the limonene synthase from Mentha spicata
I7C6Y2
homology-based protein model constructed on the 3-D crystal structure of the limonene synthase from Mentha spicata
I7CTV3
homology-based protein model constructed on the 3-D crystal structure of the limonene synthase from Mentha spicata
I7D3D7
to 1.95 A resolution, space group C2221. alpha-Helical protein comprised of 23 alpha-helices and eight 3/10 helices
A6XH05
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0
A5Y5L5
4 h, loss of about 20% of activity
718219
22
A5Y5L5
2 h, loss of about 20% of activity
718219
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Glycerol
-
10%, improves stability during the assay
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
P0DI76
expression in Escherichia coli
I3WEV8
expression in Escherichia coli
H2ELN1
expression in Escherichia coli
W8GLB1
expression in Escherichia coli
A5Y5L5
expression in Escherichia coli
-
expression in Escherichia coli
B5GMG2
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
LiCINSmRNAlevels parallel the 1,8-cineole content in mature flowers and in developmental stages
I3WEV8
regulation of gene expression by the circadian clock
A5Y5L5
daminozide significantly decreases gene expression of the monoterpene synthases sabinene synthase, borneol synthase, and 1,8-cineole synthase
O81193
expression of 1,8-cineole synthase and accumulation of its end product 1,8-cineole remain constant during the growth period until August and then decrease slightly
-
the foliar application of gibberellic acid increases gene expression of the monoterpene synthases sabinene synthase, borneol synthase, and 1,8-cineole synthase. The amounts of two of the endproducts,1,8-cineole and camphor, are directly correlated with the levels of gene expression of the respective monoterpene synthases
O81193
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
N338A
A6XH05
products are 11.7% alpha-pinene, 33.1% sabinene, 33.2% beta-pinene, 16.9% myrcene, 5.1% limonene
N338C
A6XH05
products are 16.1% alpha-pinene, 41% sabinene, 32.1% beta-pinene, 4.7% myrcene, 6.1% limonene
N338I
A6XH05
products are 6.5% alpha-pinene, 48.3% sabinene, 8.2% myrcene, 37% limonene
N338I/A339T
A6XH05
products are 5.4% alpha-pinene, 62.1% sabinene, 6.4% myrcene, 26.1% limonene
N338I/A339T/G447S
A6XH05
products are 5.7% alpha-pinene, 59.6% sabinene, 5.0% myrcene, 29.7% limonene
N338I/A339T/G447S/I449P/P450T
A6XH05
products are 86.8% sabinene, 5.5% myrcene, 7.7% limonene
N338L
A6XH05
products are 4.7% alpha-pinene, 5.6% sabinene, 13.2% beta-pinene, 27.2% myrcene, 49.3% limonene
N338S
A6XH05
products are 9.8% alpha-pinene, 34.5% sabinene, 34.2% beta-pinene, 6.8% myrcene, 2.6% limonene, 5.6% alpha-cineole, 6.5% alpha-terpineol
additional information
A6XH05
conversion of CinS1 to a sabinene synthase based on an amino acid comparison of the enzyme with Salvia officinalis SabS1 and Salvia pomifera SabS1
N338V
A6XH05
products are 61.2% sabinene, 8.0% myrcene, 30.8% limonene
additional information
-
exchange of sequences corresponding by homology to the C-terminal domain including the domain spanning alpha-helix, between sabinene synthase and both bornyl diphosphate synthase and cineole synthase. Exchange of residues 304-377 from cineole synthase into sabinene synthase is sufficient to impart the alternative termination chemistry involving water capture to alpha-terpineol and cyclization to 1,8-cineole