Information on EC 5.5.1.8 - (+)-bornyl diphosphate synthase

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The expected taxonomic range for this enzyme is: Embryophyta

EC NUMBER
COMMENTARY
5.5.1.8
-
RECOMMENDED NAME
GeneOntology No.
(+)-bornyl diphosphate synthase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
-
-
-
-
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
mechanism
-
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
linalyl diphosphate is an intermediate; mechanism; solely the diphosphate ester oxygen of geranyl diphosphate is involved in all the critical bonding processes in the coupled isomerization-cyclization
-
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
mechanism
-
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
geranyl diphosphate is first stereospecifically isomerized to linalyl diphosphate which, following rotation about C-2-B-3 to the cisoid conformer, cyclizes from the anti-endo configuration. Neryl diphosphate cyclizes either directly or via the linalyl intermediate without the attendant rotation; mechanism
-
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
both steps of the coupled isomerization-cyclization sequence are initiated by ionization of an allylic diphosphate
-
geranyl diphosphate = (+)-bornyl diphosphate
show the reaction diagram
reaction mechanism, overview
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
elimination/addition
-
-
intramolecular
-
PATHWAY
KEGG Link
MetaCyc Link
(+)-camphor biosynthesis
-
Biosynthesis of secondary metabolites
-
bornyl diphosphate biosynthesis
-
Metabolic pathways
-
Monoterpenoid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
(+)-bornyl-diphosphate lyase (decyclizing)
Requires Mg2+. The enzyme from Salvia officinalis (sage) can also use (3R)-linalyl diphosphate or more slowly neryl diphosphate in vitro [3]. The reaction proceeds via isomeration of geranyl diphosphate to (3R)-linalyl diphosphate. The oxygen and phosphorus originally linked to C-1 of geranyl diphosphate end up linked to C-2 of (+)-bornyl diphosphate [3]. cf. EC 5.5.1.22 [(-)-bornyl diphosphate synthase].
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
(+)-bornyl diphosphate synthase
-
-
(+)-bornyl diphosphate synthase
O81192
-
(+)-Bornylpyrophosphate cyclase
-
-
-
-
(+)-BPP cyclase
-
-
-
-
(-)-BPP cyclase
-
-
-
-
(di)terpene synthase
-
-
bornyl pyrophosphate synthase
-
-
-
-
bornyl pyrophosphate synthetase
-
-
-
-
Geranyl pyrophosphate:(+)-bornyl pyrophosphate cyclase
-
-
-
-
Geranyl pyrophosphate:(-)-bornyl pyrophosphate cyclase
-
-
-
-
geranyl-diphosphate cyclase
-
-
-
-
Synthetase, bornyl pyrophosphate
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
72668-91-8
-
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
metabolism
-
bornyl diphosphate synthase is responsible for the first step in camphor biosynthesis producing bornyl diphosphate, which is subsequently hydrolyzed to borneol and then oxidized to camphor, pathway overview
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(+)-(3S)-Linalyl diphosphate
(-)-(1S,4S)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
(-)-(3R)-Linalyl diphosphate
(+)-(1R,4R)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
O81192
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
(+)-(1R,4R)-bornyl-diphosphate
-
Geranyl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
geranyl diphosphate is preferred over neryl diphosphate
-
-
Geranyl diphosphate
(-)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(-)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(-)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
Geranyl diphosphate
(-)-Bornyl-diphosphate
show the reaction diagram
-
-
(-)-(1S,4S)-bornyl-diphosphate
-
Geranyl diphosphate
?
show the reaction diagram
-
formation of bornyl diphosphate is the rate-limiting step in camphor biosynthesis even in immature leaf tissue
-
-
-
geranyl diphosphate
(+)-bornyl diphosphate
show the reaction diagram
-
-
-
-
?
geranyl diphosphate
(+)-bornyl diphosphate
show the reaction diagram
-
-
the enzyme is involved in monoterpenoid cyclase catalysis, mechanism of this coupled isomerization-cyclization reaction, modeling, overview
-
?
geranyl diphosphate
(+)-bornyl diphosphate
show the reaction diagram
-
cyclization
-
-
?
Neryl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
-
-
-
Neryl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
-
(+)-(1R,4R)-bornyl diphosphate
-
Neryl diphosphate
(+)-Bornyl-diphosphate
show the reaction diagram
-
geranyl diphosphate is preferred over neryl diphosphate
-
-
geranyl diphosphate
(+)-bornyl diphosphate
show the reaction diagram
-
bornyl diphosphate synthase is an unusual example of a monoterpene synthase, because the diphosphate leaving group of the geranyl substrate is recaptured in the final product
-
-
?
additional information
?
-
-
the C-terminal domain catalyzes the cyclization of geranyl diphosphate, orienting and stabilizing multiple reactive carbocation intermediates. The N-terminal domain has no clearly defined function, although its N-terminus caps the active site in the C-terminal domain during catalysis
-
?
additional information
?
-
-
the reaction mechanism in BPPS involves the following steps: binding of geranyl diphospahte, metal-activated ionization to yield an allylic transoid carbocation, formation of (3R)-linalyl diphosphate, rotation around the C2-C3 bond and ionization to generate a cisoid allylic cation in the reactive conformation, cyclization to form a (4R)-R-terpinyl cation, further cyclization to yield (+)-2-bornyl cation, and reincorporation of the diphosphate by the (+)-2-bornyl carbocation, to yield the final product (+)-bornyl diphosphate in ca. 75% yield
-
-
-
additional information
?
-
-
(di)terpene synthases seem to mediate specific reaction outcomes, at least in part, by providing electrostatic effects to counteract those exerted by the diphosphate co-product. Role for the diphosphate anion co-product in the reaction catalyzed by monoterpene cyclases, such as bornyl diphosphate synthase, hydroxyl dipole stabilization of the specific carbocation formed by initial cyclization, enabling deprotonation of this early intermediate, whereas the lack of such stabilization, i.e. in the presence of an aliphatic side chain leads to carbocation migration towards the pyrophosphate co-product, resulting in a more complex reaction. The 7-aza-7,8-dihydrolimonene analogue is clearly bound backwards to enable aza-diphosphate ion-pairing, indicating that this is the thermodynamically favored binding mode for such a carbocation. The diphosphate co-product is tightly bound and may serve as a general acid/base during terpene synthase reactions without becoming reattached itself. Consistent with such tight binding is the stereospecificity of bornyl diphosphate formation by BPS, which reattaches the bornyl cation to the same oxygen of the diphosphate involved in the original diphosphate ester bond of the GPP substrate, indicating that the diphosphate anion remains in a fixed orientation during the catalyzed reaction
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
Geranyl diphosphate
?
show the reaction diagram
-
formation of bornyl diphosphate is the rate-limiting step in camphor biosynthesis even in immature leaf tissue
-
-
-
geranyl diphosphate
(+)-bornyl diphosphate
show the reaction diagram
-
-
the enzyme is involved in monoterpenoid cyclase catalysis, mechanism of this coupled isomerization-cyclization reaction, modeling, overview
-
?
geranyl diphosphate
(+)-bornyl diphosphate
show the reaction diagram
-
cyclization
-
-
?
additional information
?
-
-
(di)terpene synthases seem to mediate specific reaction outcomes, at least in part, by providing electrostatic effects to counteract those exerted by the diphosphate co-product. Role for the diphosphate anion co-product in the reaction catalyzed by monoterpene cyclases, such as bornyl diphosphate synthase
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
Km: 3.5 mM; required
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
(3R)-homolinalyl diphosphate
-
i.e. 2,6-dimethyl-2-vinyl-5-heptenyl diphosphate
(3R,S)2-fluorolinalyl diphosphate
-
-
(3S)-homolinalyl diphosphate
-
i.e. 2,6-dimethyl-2-vinyl-5-heptenyl diphosphate
(E)-4-[2-Diazo-3-trifluoropropionyloxy]-3-methyl-2-buten-1-ol
-
-
2,3-Dihydrogeranyl diphosphate
-
-
2,3-Epoxygeranyl diphosphate
-
-
2-Fluorogeranyl diphosphate
-
-
2-Fluorolinalyl diphosphate
-
-
3-aza-2,3-dihydrogeranyl diphosphate
-
competitive inhibition, the aza-analog of the substrate is bound anomalously, perhaps as a consequence of the positive charge, bond distortion, or hydrogen bonding resulting from the N for C substitution, binding strutcure, overview
6,7-Dihydrogeranyl diphosphate
-
-
6,7-Epoxygeranyl diphosphate
-
-
6-Cyclopropylidene-3E-methyl-hex-2-en-1-yl diphosphate
-
about 50% inhibition at 0.01 mM for 20 min
diisopropylfluorophosphate
-
-
Dimethyl-(4-methylcyclohex-3-en-1-yl)sulfonium iodide
-
-
Dimethyl-(4-methylcyclohex-3-en-1-yl)sulfonium iodide
-
potency of inhibition increases with increasing substrate concentration. A combination of sulfonium analog and 0.05 mM diphosphate provides synergistic inhibition
dimethylallyl diphosphate
-
-
Diphosphoric acid
-
-
Imidodiphosphonic acid
-
-
Linalyl diphosphate
-
competitive inhibition, the enantioselective synthase readily distinguishes between (3R)- and (3S)-homolinalyl diphosphates, both of which were more effective inhibitors than is 3-azageranyl diphosphate, the fluorinated analogues prove to be the most potent competitive inhibitors
Methyl-(4-methylpent-3-en-1-yl)vinyl sulfonium perchlorate
-
potency of inhibition increases with increasing substrate concentration. A combination of sulfonium analog and 0.05 mM diphosphate provides synergistic inhibition
Methylenediphosphonic acid
-
-
p-hydroxymercuribenzoate
-
-
Phosphonoformic acid
-
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0032
-
(+)-(3S)-Linalyl diphosphate
-
-
0.007
-
(+)-(3S)-Linalyl diphosphate
-
-
0.0007
-
(-)-(3R)-Linalyl diphosphate
-
-
0.0011
-
geranyl diphosphate
-
-
0.0014
-
geranyl diphosphate
-
-
0.0023
-
geranyl diphosphate
-
-
0.0037
-
neryl diphosphate
-
-
0.0121
-
neryl diphosphate
-
-
0.018
-
neryl diphosphate
-
-
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.214
-
(3R)-homolinalyl diphosphate
-
-
0.058
-
(3R,S)2-fluorolinalyl diphosphate
-
-
1.2
-
(3S)-homolinalyl diphosphate
-
-
0.006
-
2-Fluorogeranyl diphosphate
-
-
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
6.2
-
-
geranyl diphosphate and neryl diphosphate, the maximal activity with geranyl diphosphate is about 5times higher than with neryl diphosphate
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
5.7
6.7
-
pH 5.7: about 40% of maximal activity, pH 6.7: about 35% of maximal activity, geranyl diphosphate
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
epidermal gland
Manually annotated by BRENDA team
-
the second leaf pair to emerge beyond the cotyledon from 21-day-old plants
Manually annotated by BRENDA team
-
unfurled leaves from the shoot apex
Manually annotated by BRENDA team
-
rapidly expanding leaves from the shoot apex
Manually annotated by BRENDA team
-
expending leaves from 4- to 6-week-old plants
Manually annotated by BRENDA team
-
especially in young leaves, expression pattern analysis, overview
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
95000
-
-
gel filtration
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
dimer
-
each monomer contains two alpha-helical domains
additional information
-
analysis of tertiary crystal structures of bornyl diphosphate synthase, the aza moiety is ion-paired with the diphosphate, whose position is essentially invariant
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
analysis of tertiary crystal structures of bornyl diphosphate synthase complexed with diphosphate and/or aza-analogs, mimicking various carbocations of the BPS catalyzed reaction
-
hanging-drop vapor-diffusion method, structure of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with diphosphate and bornyl diphosphate, determined at 2.0 A resolution
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
dye-ligand and immobilized metal ion interaction chromatography
-
mechanized techniques for the selective extraction of enzymes from plant epidermal glands
-
recombinant enzyme from Escherichia coli
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
expression in Escherichia coli
-
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
the enzyme is induced by gibberellic acids I and II in leaves, especially in young leaves
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
additional information
-
the recombinant enzyme is similarly truncated at E50 to provide a pseudomature form devoid of the plastid transit peptide