Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 1.21.3.7 - tetrahydrocannabinolic acid synthase and Organism(s) Cannabis sativa and UniProt Accession Q8GTB6

for references in articles please use BRENDA:EC1.21.3.7
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
A flavoprotein (FAD). The cofactor is covalently bound. Part of the cannabinoids biosynthetic pathway in the plant Cannabis sativa. The enzyme can also convert cannabinerolate (the (Z)-isomer of cannabigerolate) to Delta9-THCA with lower efficiency. Whereas the product was originally called Delta1-tetrahydrocannabinolate, the recommended name according to systematic peripheral numbering is Delta9-tetrahydrocannabinolate.
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Cannabis sativa
UNIPROT: Q8GTB6
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Cannabis sativa
The enzyme appears in selected viruses and cellular organisms
Synonyms
thca synthase, thcas, tetrahydrocannabinolic acid synthase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
DELTA1-tetrahydrocannabinolic acid synthase
-
DELTA9-tetrahydrocannabinolic acid synthase
-
tetrahydrocannabinolic acid-synthase
-
THCA-synthase
-
DELA1-THCA synthase
-
-
DELTA1-tetrahydrocannabinolic acid synthase
DELTA9-tetrahydrocannabinolic acid synthase
-
-
tetrahydrocannabinolic acid synthase
-
-
tetrahydrocannabinolic-acid synthase
-
-
THCA synthase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
oxidative cyclization
SYSTEMATIC NAME
IUBMB Comments
cannabigerolate:oxygen oxidoreductase (cyclizing, DELTA9-tetrahydrocannabinolate-forming)
A flavoprotein (FAD). The cofactor is covalently bound. Part of the cannabinoids biosynthetic pathway in the plant Cannabis sativa. The enzyme can also convert cannabinerolate (the (Z)-isomer of cannabigerolate) to Delta9-THCA with lower efficiency. Whereas the product was originally called Delta1-tetrahydrocannabinolate, the recommended name according to systematic peripheral numbering is Delta9-tetrahydrocannabinolate.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
cannabigerolate + O2
DELTA9-tetrahydrocannabinolate + H2O2
show the reaction diagram
cannabigerolate + O2
DELTA9-tetrahydrocannabinolate + H2O2
show the reaction diagram
cannabinerolate + O2
DELTA9-tetrahydrocannabinolate + H2O2
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
cannabigerol and cannabinero are no substrates
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
cannabigerolate + O2
DELTA9-tetrahydrocannabinolate + H2O2
show the reaction diagram
cannabigerolate + O2
DELTA9-tetrahydrocannabinolate + H2O2
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
cannabigerolate
-
substrate inhibition
Fe3+
-
91% residual activity at 2 mM Fe3+
Hg2+
-
strong inhibitor, 4% residual activity at 2 mM Hg2+
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
BSA
-
the addition of BSA has a slightly positive effect on the activity of the enzyme
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.446 - 0.783
cannabigerolate
0.0084 - 0.134
cannabigerolate
0.254
cannabinerolate
-
at pH 6.0, temperature not specified in the publication
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.043 - 0.3
cannabigerolate
0.308 - 0.888
cannabigerolate
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.096 - 0.556
cannabigerolate
6.78
cannabigerolate
-
recombinant enzyme, in 100 mM sodium citrate (pH 5.5), at 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.078
-
unpurified recombinant enzyme, in 100 mM sodium citrate (pH 5.5), at 30°C
0.41
-
recombinant enzyme after 5250fold purification, in 100 mM sodium citrate (pH 5.5), at 30°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 6
-
-
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.4
-
isoelectric focusing
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
fresh leaves from young cannabis plants display the lowest tetrahydrocannybinolic acid synthase gene expression
Manually annotated by BRENDA team
-
the enzyme is localized to and functions in the storage cavity of glandular trichomes
Manually annotated by BRENDA team
additional information
-
samples composed of a mixture of leaves and tops of fresh adult cannabis plants and seized marijuana display the highest lowest tetrahydrocannybinolic acid synthase gene expression
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
key enzyme in the synthesis of tetrahydrocannabinolate
physiological function
-
a key enzyme controlling the psychoactivity of cannabis
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
THCAS_CANSA
545
1
61927
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
58597
x * 58597, mature protein, calculate from amino acid sequence
58600
x * 58600, calculated from amino acid sequence
60000
75000
x * 75000, native enzyme, SDS-PAGE
58600
-
x * 58600, mature enzyme, calculated from amino acid sequence
59000
-
x * 59000, deglycosylated enzyme, SDS-PAGE
74000
-
gel filtration
75000
-
1 * 75000, SDS-PAGE
76000
-
about 76000 Da, gel filtration
79000
-
x * 79000, glycosylated enzyme, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
glycoprotein
-
the enzyme contains seven possible Asn glycosylation sites. Endoglycosidase treatment affords a deglycosylated enzyme with more catalytic activity than that of the glycosylated form
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting drop vapor diffusion method, in 0.09 M HEPES buffer pH 7.5 containing 1.26 M sodium citrate
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H114A
the inactive mutant contains no FAD
H208A
the mutant shows 94% wild type activity
H92A
the mutant shows 87% wild type activity
R108A
the mutant shows 13% wild type activity
R110A
the mutant shows 10% wild type activity
E442Q
-
the enzyme shows 85% of wild type activity
H114A
-
the mutation completely abolishes enzymatic activity
H292A
-
the enzyme shows 5% of wild type activity
Y417F
-
the enzyme shows 42% of wild type activity
Y484F
-
the mutation completely abolishes enzymatic activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
the enzyme remains stable after 9 h at 37°C
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hydroxylapatite column chromatography
Toyopearl CM-650 column chromatography, gel filtration
DE-52 column chromatography, phenyl Sepharose CL-4B column chromatography, and hydroxylapatite column chromatography
-
diethylaminoethyl-cellulose column chromatography, phenyl Sepharose CL-4B column chromatography, and hydroxylapatite column chromatography
-
hydroxylapatite column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) and Pichia pastoris MutSKM71 KE1 cells
expressed in Pichia pastoris KM71 KE1 ccells
expressed in Saccharomyces cerevisiae strain CEN.PK2-1C and Pichia pastoris strain PichiaPink2
expressed in Sf9 insect cells
using a baculovirus-Sf9 insect cell expression system and expressed in Nicotiana tabacum hairy roots
expressed in Nicotiana tabacum BY-2 cells
-
expressed in Pichia pastoris KM71 KE1 cells
-
expressed in Saccharomyces cerevisiae and Komagataella phaffii
-
expressed in Sf9 insect cells
-
expressed in the methylotrophic Pichia pastoris strain SMD1168h
-
expressed using a baculovirus insect expression system and expressed in transgenic Nicotiana tabacum hairy roots and methylotrophic yeast Pichia pastoris
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the secreted enzyme activity in Pichia pastoris cultures is increased to 472% in the presence of 0.5% (w/v) casamino acids, 277% in the presence of proteinase inhibitors (10 mg/l 4-(2-aminoethyl) benzensulfonyl fluoride, 1 mg/l pepstatin A, and 1 mg/l E-64), 226% in the presence of 10 mg/ml FAD, 248% in the presence of 10 mg/ml FMN, 323% in the presence of 10 mg/ml riboflavin, and 298% in the presence of 1% (v/v) methanol
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shoyama, Y.; Takeuchi, A.; Taura, F.; Tamada, T.; Adachi, M.; Kuroki, R.; Shoyama, Y.; Morimoto, S.
Crystallization of Delta1-tetrahydrocannabinolic acid (THCA) synthase from Cannabis sativa
Acta Crystallogr. Sect. F
61
799-801
2005
Cannabis sativa (Q8GTB6), Cannabis sativa
Manually annotated by BRENDA team
Taura, F.; Dono, E.; Sirikantaramas, S.; Yoshimura, K.; Shoyama, Y.; Morimoto, S.
Production of DELTA1-tetrahydrocannabinolic acid by the biosynthetic enzyme secreted from transgenic Pichia pastoris
Biochem. Biophys. Res. Commun.
361
675-680
2007
Cannabis sativa
Manually annotated by BRENDA team
Taura, F.
Studies on tetrahydrocannabinolic acid synthase that produces the acidic precursor of tetrahydrocannabinol, the pharmacologically active cannabinoid in marijuana
Drug Discov. Ther.
3
83-87
2009
Cannabis sativa
Manually annotated by BRENDA team
Taura, F.; Sirikantaramas, S.; Shoyama, Y.; Yoshikai, K.; Shoyama, Y.; Morimoto, S.
Cannabidiolic-acid synthase, the chemotype-determining enzyme in the fiber-type Cannabis sativa
FEBS Lett.
581
2929-2934
2007
Cannabis sativa
Manually annotated by BRENDA team
Taura, F.; Morimoto, S.; Shoyama, Y.; Mechoulam, R.
First direct evidence for the mechanism of DELTA1-tetrahydrocannabinolic acid biosynthesis
J. Am. Chem. Soc.
117
9766-9767
1995
Cannabis sativa
-
Manually annotated by BRENDA team
Sirikantaramas, S.; Morimoto, S.; Shoyama, Y.; Ishikawa, Y.; Wada, Y.; Shoyama, Y.; Taura, F.
The gene controlling marijuana psychoactivity: molecular cloning and heterologous expression of DELTA1-tetrahydrocannabinolic acid synthase from Cannabis sativa L.
J. Biol. Chem.
279
39767-39774
2004
Cannabis sativa (Q8GTB6), Cannabis sativa
Manually annotated by BRENDA team
Shoyama, Y.; Tamada, T.; Kurihara, K.; Takeuchi, A.; Taura, F.; Arai, S.; Blaber, M.; Shoyama, Y.; Morimoto, S.; Kuroki, R.
Structure and function of DELTA1-tetrahydrocannabinolic acid (THCA) synthase, the enzyme controlling the psychoactivity of Cannabis sativa
J. Mol. Biol.
423
96-105
2012
Cannabis sativa
Manually annotated by BRENDA team
Sirikantaramas, S.; Taura, F.; Tanaka, Y.; Ishikawa, Y.; Morimoto, S.; Shoyama, Y.
Tetrahydrocannabinolic acid synthase, the enzyme controlling marijuana psychoactivity, is secreted into the storage cavity of the glandular trichomes
Plant Cell Physiol.
46
1578-1582
2005
Cannabis sativa
Manually annotated by BRENDA team
Cascini, F.; Passerotti, S.; Boschi, I.
Analysis of THCA synthase gene expression in cannabis: a preliminary study by real-time quantitative PCR
Forensic Sci. Int.
231
208-212
2013
Cannabis sativa
Manually annotated by BRENDA team
Alaoui, M.A.; Ibrahimi, A.; Semlali, O.; Tarhda, Z.; Marouane, M.; Najwa, A.; Soulaymani, A.; Fahime, E.E.
Affinity comparison of different THCA synthase to CBGA using modeling computational approaches
Bioinformation
10
33-38
2014
Cannabis sativa (Q8GTB6), Cannabis sativa
Manually annotated by BRENDA team
Zirpel, B.; Stehle, F.; Kayser, O.
Production of DELTA9-tetrahydrocannabinolic acid from cannabigerolic acid by whole cells of Pichia (Komagataella) pastoris expressing DELTA9-tetrahydrocannabinolic acid synthase from Cannabis sativa L.
Biotechnol. Lett.
37
1869-1875
2015
Cannabis sativa (Q8GTB6)
Manually annotated by BRENDA team
Lange, K.; Poetsch, A.; Schmid, A.; Julsing, M.K.
Enrichment and identification of DELTA9-tetrahydrocannabinolic acid synthase from Pichia pastoris culture supernatants
Data Brief
4
641-649
2015
Cannabis sativa (Q8GTB6)
Manually annotated by BRENDA team
Lange, K.; Schmid, A.; Julsing, M.K.
DELTA9-Tetrahydrocannabinolic acid synthase production in Pichia pastoris enables chemical synthesis of cannabinoids
J. Biotechnol.
211
68-76
2015
Cannabis sativa (Q8GTB6)
Manually annotated by BRENDA team
Lange, K.; Schmid, A.; Julsing, M.K.
DELTA9-Tetrahydrocannabinolic acid synthase The application of a plant secondary metabolite enzyme in biocatalytic chemical synthesis
J. Biotechnol.
233
42-48
2016
Cannabis sativa
Manually annotated by BRENDA team
Zirpel, B.; Degenhardt, F.; Martin, C.; Kayser, O.; Stehle, F.
Engineering yeasts as platform organisms for cannabinoid biosynthesis
J. Biotechnol.
259
204-212
2017
Cannabis sativa
Manually annotated by BRENDA team
Cirovic, N.; Kecmanovic, M.; Keckarevic, D.; Keckarevic Markovic, M.
Differentiation of Cannabis subspecies by THCA synthase gene analysis using RFLP
J. Forensic Leg. Med.
51
81-84
2017
Cannabis sativa (Q8GTB6), Cannabis sativa, Cannabis sativa subsp. indica
Manually annotated by BRENDA team
Onofri, C.; de Meijer, E.P.M.; Mandolino, G.
Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype
Phytochemistry
116
57-68
2015
Cannabis sativa (Q8GTB6), Cannabis sativa
Manually annotated by BRENDA team