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Information on EC 2.1.1.159 - theobromine synthase and Organism(s) Coffea arabica and UniProt Accession Q84PP7
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2.1.1.159 theobromine synthaseIUBMB Comments
This is the third enzyme in the caffeine-biosynthesis pathway. This enzyme can also catalyse the conversion of paraxanthine into caffeine, although the paraxanthine pathway is considered to be a minor pathway for caffeine biosynthesis [2,3].
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Word Map
- 2.1.1.159
- purine
- camellia
- xanthosine
- coffea
- 1,3,7-trimethylxanthine
- arabica
- n-methyltransferases
-
caffeine-free
- rnai
- food industry
-
planta
- canephora
-
germplasms
- sinensis
- biotechnology
- agriculture
The taxonomic range for the selected organisms is: Coffea arabica
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
theobromine synthase, 7-methylxanthine methyltransferase, 3,7-dimethylxanthine methyltransferase, 3-n-methyltransferase, caffeine synthase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
7-methylxanthine methyltransferase
PATHWAY SOURCE
PATHWAYS
KEGG
-
-, -
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:7-methylxanthine N3-methyltransferase
This is the third enzyme in the caffeine-biosynthesis pathway. This enzyme can also catalyse the conversion of paraxanthine into caffeine, although the paraxanthine pathway is considered to be a minor pathway for caffeine biosynthesis [2,3].
CAS REGISTRY NUMBER
COMMENTARY
72270-63-4
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
S-adenosyl-L-methionine + 1,7-dimethylxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. paraxanthine
i.e. caffeine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway, theobromine is the major intermediate for caffeine biosynthesis
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
preferred substrate, 20fold higher activity by isozyme MXMT2 compared to activity with paraxanthine
i.e. theobromine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
low activity by isozyme MXMT2
i.e. caffeine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
-
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
Q8H0G0
-
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
second step in caffeine biosynthesis pathway
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway from xanthosine
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway, theobromine is the major intermediate for caffeine biosynthesis
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
Q8H0G0
step of the caffeine biosynthesis, caffeine accumulation in seeds
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
third step in caffeine biosynthesis pathway from xanthosine
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
preferred substrate, 3fold higher activity by isozyme MXMT1 compared to activity with paraxanthine
i.e. theobromine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
?
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
low activity
i.e. caffeine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
low activity by isozyme MXMT1
i.e. caffeine
-
ir
additional information
?
-
bifunctional enzyme performing 3-N-methyltransferase activity, EC 2.1.1.159, and 1-N-methyltransferase activity, EC 2.1.1.160, overview
-
-
?
additional information
?
-
Q8H0G0
enzyme expression and activity during caffeine biosynthesis in fruits, overview
-
-
?
additional information
?
-
-
feeding experiments with fruit samples, determination of reaction products, overview
-
-
?
additional information
?
-
substrate specificity, bifunctional enzyme performing 3-N-methyltransferase activity, EC 2.1.1.159, and 1-N-methyltransferase activity, EC 2.1.1.160, overview
-
-
?
additional information
?
-
-
substrate specificity, overview, no activity with xanthine, hypoxanthine, and xanthosine
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
ir
S-adenosyl-L-methionine + 1,7-dimethylxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. paraxanthine
i.e. caffeine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway, theobromine is the major intermediate for caffeine biosynthesis
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
-
second step in caffeine biosynthesis pathway
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway from xanthosine
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
second step in caffeine biosynthesis pathway, theobromine is the major intermediate for caffeine biosynthesis
i.e. theobromine
-
ir
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
Q8H0G0
step of the caffeine biosynthesis, caffeine accumulation in seeds
i.e. theobromine
-
?
S-adenosyl-L-methionine + 7-methylxanthine
S-adenosyl-L-homocysteine + 3,7-dimethylxanthine
third step in caffeine biosynthesis pathway from xanthosine
i.e. theobromine
-
?
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
ir
S-adenosyl-L-methionine + paraxanthine
S-adenosyl-L-homocysteine + 1,3,7-trimethylxanthine
-
i.e. caffeine
-
ir
additional information
?
-
bifunctional enzyme performing 3-N-methyltransferase activity, EC 2.1.1.159, and 1-N-methyltransferase activity, EC 2.1.1.160, overview
-
-
?
additional information
?
-
Q8H0G0
enzyme expression and activity during caffeine biosynthesis in fruits, overview
-
-
?
additional information
?
-
-
feeding experiments with fruit samples, determination of reaction products, overview
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-chloromercuribenzoate
-
complete inhibition at 0.5 mM, 30% inhibition at 0.05 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
determination of in vivo activity in wild-type and mutant plants by determination of theobromine concentration in seedlings and young leaves
additional information
determination of in vivo activity in wild-type and mutant plants by determination of theobromine concentration in seedlings and young leaves
additional information
-
determination of in vivo activity in wild-type and mutant plants by determination of theobromine concentration in seedlings and young leaves
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
high expression in young leaves of isozyme MXTM2, low expression level in expanded leaves
additional information
Q8H0G0
immature, ripening, and mature, enzyme expression and activity during development, overview
high expression level of MXMT in young leaves, low expression level in old leaves
very high expression in young leaves of isozyme MXTM1, low expression level in expanded leaves
additional information
method development for somatic embryogenesis, overview
additional information
method development for somatic embryogenesis, overview
additional information
-
method development for somatic embryogenesis, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
co-localization of xanthosine methyltransferase, 7-methylxanthine methyltransferase, and 3,7-dimethylxanthine methyltransferase
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). MXMT2_COFAR
384
0
43472
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
dimer
-
bimolecular fluorescence complementation. Enzymes xanthosine methyltransferase, 7-methylxanthine methyltransferase, and 3,7-dimethylxanthine methyltransferase each form a homo-dimer in cytosol. In addition, each enzyme also forms a hetero-dimer with each of the other two enzymes in cytosol
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
suppression of enzyme expression by RNA interference method, method development for somatic embryogenesis, Agrobacterium tumefaciens-mediated transformation, the transgenic plants show reduced caffeine content, overview
additional information
suppression of enzyme expression by RNA interference method, method development for somatic embryogenesis, Agrobacterium tumefaciens-mediated transformation, the transgenic plants show reduced caffeine content, overview
additional information
-
suppression of enzyme expression by RNA interference method, method development for somatic embryogenesis, Agrobacterium tumefaciens-mediated transformation, the transgenic plants show reduced caffeine content, overview
additional information
transgenic Nicotiana tabacum plant leaves expressing all three enzymes required for the biosynthesis of caffeine are no longer eaten by the tobacco cutworm caterpillars, Spodoptera litura, overview
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
native enzyme 39fold from young leaves by ammonium sulfate fractionation, 3 steps of ion exchange chromatography, and gel filtration
-
recombinant GST-fusion enzyme from Escherichia coli strain JM109 by glutathione affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene MXMT2, DNA and amino acid sequence determination and analysis
isozyme MXMT2, DNA and amino acid sequence determination and analysis, phylogenetic analysis, expression of the GST-tagged isozymes in Escherichia coli Bl21(DE3)
DNA and amino acid sequence determination and analysis, cloning of MXMT vectors for Agrobacterium tumefaciens-mediated transformation
DNA and amino acid sequence determination and analysis, expression in Escherichia coli as wild-type and as Trx-fusion protein
gene CaMTL2, cDNA library construction, DNA and amino acid sequence determination and analysis
gene CaMXMT, cDNA library construction, DNA and amino acid sequence determination and analysis, sequence comparison with other species, expression of CaMXMT as GST-fusion enzyme in Escherichia coli strain JM109
isozyme MXMT1, DNA and amnio acid sequence determination and analysis, phylogenetic analysis, expression of the GST-tagged isozymes in Escherichia coli Bl21(DE3)
isozyme MXMT1, functional expression in transgenic Nicotiana tabacum plant leaves
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
naturally occuring low-caffeine fruits have a lower expression of the theobromine synthase and caffeine synthase genes and also contain an extra transcript of the caffeine synthase gene encoding a mutant form. The absence of caffeine in these mutants probably results from a combination of transcriptional regulation and the presence of mutations
Q8H0G0
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
expression of the caffeine biosynthesis enzymes in transgenic crop plants may protect against the crop damaging larvae of pests
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mizuno, K.; Okuda, A.; Kato, M.; Yoneyama, N.; Tanaka, H.; Ashihara, H.; Fujimura, T.
Isolation of a new dual-functional caffeine synthase gene encoding an enzyme for the conversion of 7-methylxanthine to caffeine from coffee (Coffea arabica L.)
FEBS Lett.
534
75-81
2003
Coffea arabica (Q8H0D3)
Ogawa, M.; Herai, Y.; Koizumi, N.; Kusano, T.; Sano, H.
7-Methylxanthine methyltransferase of coffee plants. Gene isolation and enzymatic properties
J. Biol. Chem.
276
8213-8218
2001
Coffea arabica (Q9AVJ9), Coffea arabica (Q9AVK1)
Roberts, M.F.; Waller, G.R.
N-methyltransferases and 7-methyl-N9-nucleoside hydrolase activity in Coffea arabica and the biosynthesis of caffeine
Phytochemistry
18
451-455
1979
Coffea arabica
-
Waldhauser, S.S.M.; Gillies, F.M.; Crozier, A.; Baumann, T.W.
Separation of the N-7 methyltransferase, the key enzyme in caffeine biosynthesis
Phytochemistry
45
1407-1414
1997
Coffea arabica
Ogita, S.; Uefuji, H.; Morimoto, M.; Sano, H.
Application of RNAi to confirm theobromine as the major intermediate for caffeine biosynthesis in coffee plants with potential for construction of decaffeinated varieties
Plant Mol. Biol.
54
931-941
2004
Coffea canephora, Coffea arabica (Q84PP7), Coffea arabica (Q9AVJ9), Coffea arabica
Uefuji, H.; Tatsumi, Y.; Morimoto, M.; Kaothien-Nakayama, P.; Ogita, S.; Sano, H.
Caffeine production in tobacco plants by simultaneous expression of three coffee N-methyltranferases and its potential as a pest repellant
Plant Mol. Biol.
59
221-227
2005
Coffea arabica (Q9AVJ9)
Uefuji, H.; Ogita, S.; Yamaguchi, Y.; Koizumi, N.; Sano, H.
Molecular cloning and functional characterization of three distinct N-methyltransferases involved in the caffeine biosynthetic pathway in coffee plants
Plant Physiol.
132
372-380
2003
Coffea arabica (Q84PP7), Coffea arabica (Q9AVJ9)
Koshiro, Y.; Zheng, X.Q.; Wang, M.L.; Nagai, C.; Ashihara, H.
Changes in content and biosynthetic activity of caffeine and trigonelline during growth and ripening of Coffea arabica and Coffea canephora fruits
Plant Sci.
171
242-250
2006
Coffea canephora, Coffea arabica (Q8H0G0)
Kodama, Y.; Shinya, T.; Sano, H.
Dimerization of N-methyltransferases involved in caffeine biosynthesis
Biochimie
90
547-551
2008
Coffea arabica
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