Information on EC 1.14.11.32 - codeine 3-O-demethylase

for references in articles please use BRENDA:EC1.14.11.32
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The expected taxonomic range for this enzyme is: Papaver

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EC NUMBER
COMMENTARY hide
1.14.11.32
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RECOMMENDED NAME
GeneOntology No.
codeine 3-O-demethylase
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REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
codeine + 2-oxoglutarate + O2 = morphine + formaldehyde + succinate + CO2
show the reaction diagram
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
morphine biosynthesis
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Isoquinoline alkaloid biosynthesis
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Metabolic pathways
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Biosynthesis of secondary metabolites
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SYSTEMATIC NAME
IUBMB Comments
codeine,2-oxoglutarate:oxygen oxidoreductase (3-O-demethylating)
Requires Fe2+. Catalyses a step in morphine biosynthesis. The enzyme also catalyses the 3-O-demethylation of thebaine to oripavine, with lower efficiency.
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
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the enzyme belongs to the 2-oxoglutarate/Fe(II)-dependent dioxygenase superfamily
malfunction
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virus-induced gene silencing of CODM in opium poppy efficiently blocks metabolism at codeine
metabolism
physiological function
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codeine O-demethylase catalyzes the last step of morphine biosynthesis in opium poppy, but it also catalyze the O,O-demethylenation of methylenedioxy bridges on protopine alkaloids. No or poor activity with papaverine, (R,S)-tetrahydropapaverine, (R,S)-canadine, (R,S)-stylopine, berberine, and oripavine
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R,S)-tetrahydropalmatine + 2-oxoglutarate + O2
?
show the reaction diagram
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a protoberberine, O-demethylation, 16.6% of activity with protopine
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?
(S)-isocorydine + 2-oxoglutarate + O2
?
show the reaction diagram
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a aporphine, O-demethylation, 6.1% of activity with protopine
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?
(S)-reticuline + 2-oxoglutarate + O2
?
show the reaction diagram
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a 1-benzylisoquinoline, O-demethylation, 16.2% of activity with protopine
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?
(S)-scoulerine + 2-oxoglutarate + O2
?
show the reaction diagram
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a 1-benzylisoquinoline, O-demethylation, 70.4% of activity with protopine
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?
allocryptopine + 2-oxoglutarate + O2
?
show the reaction diagram
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a protopine, O-demethylation, 50.1% of activity with protopine
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?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
show the reaction diagram
cryptopine + 2-oxoglutarate + O2
?
show the reaction diagram
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a protopine, O-demethylation, 37.7% of activity with protopine
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?
neopine + 2-oxoglutarate + O2
neomorphine + formaldehyde + succinate + CO2
show the reaction diagram
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O-demethylcryptopine + 2-oxoglutarate + O2
?
show the reaction diagram
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a protopine, O-demethylation, 40.8% of activity with protopine
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?
protopine + 2-oxoglutarate + O2
?
show the reaction diagram
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best substrate
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?
scoulerine + 2-oxoglutarate + O2
3-O-demethylscoulerine + formaldehyde + succinate + CO2
show the reaction diagram
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120% of the activity with codeine
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?
thebaine + 2-oxoglutarate + O2
?
show the reaction diagram
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a morphinan, O-demethylation, 80.5% of activity with protopine
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?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
show the reaction diagram
thebaine + 2-oxoglutarate + O2
oripavine + succinate + CO2
show the reaction diagram
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?
additional information
?
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no activity with (S)-reticuline, papaverine, (S)-corytuberine, pavine, salutaridine, oripavine, noscapine
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NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
show the reaction diagram
neopine + 2-oxoglutarate + O2
neomorphine + formaldehyde + succinate + CO2
show the reaction diagram
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?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
show the reaction diagram
thebaine + 2-oxoglutarate + O2
oripavine + succinate + CO2
show the reaction diagram
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?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
thebaine
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ascorbate
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.019
2-oxoglutarate
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pH 7.4, 30°C
0.0205 - 0.0728
codeine
0.0419 - 0.216
thebaine
additional information
additional information
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steady-state enzyme kinetics of purified recombinant CODM using (S)-scoulerine as substrate
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.011
2-oxoglutarate
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pH 7.4, 30°C
0.0161
codeine
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pH 7.4, 30°C
0.0099
thebaine
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pH 7.4, 30°C
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
578.9
2-oxoglutarate
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pH 7.4, 30°C
0.00095 - 785.4
codeine
0.000015 - 235.2
thebaine
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.642
codeine
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pH 7.4, 30°C
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type enzyme and mutants from Escherichia coli strain SG13009 by cobalt affinity chromatography
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Saccharomyces cerevisiae strain GCY1358
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expression of His-tagged wild-type enzyme and mutants in Escherichia coli strain SG13009
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His6-tagged protein is produced in Escherichia coli
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phylogenetic tree, CODM real time quantitative PCR expression analysis, recombinant expression
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
endophyte SM3B (Marmoricola sp.) can enhance enzyme expression by 2fold
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enzyme expression is significantly up-regulated with methyl jasmonate and salicylic acid treatments at 48 h
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E338G/I340L/L341V/K342E
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site-directed mutagenesis, the mutant exhibits demethylase activity exclusively toward codeine, not also toward thebaine like the wild-type enzyme
R334S/R336S
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site-directed mutagenesis, the mutant retains O-demethylase activity toward either thebaine or codeine like the wild-type enzyme
R334S/R336T
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site-directed mutagenesis, the mutant retains O-demethylase activity toward either thebaine or codeine like the wild-type enzyme
S149M/L151F/S152T
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site-directed mutagenesis, the mutant is expressed at low levels, perhaps due to improper folding
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LINKS TO OTHER DATABASES (specific for EC-Number 1.14.11.32)
ExplorEnz
ExPASy
KEGG
MetaCyc
SABIO-RK
NCBI: PubMed, Protein, Nucleotide, Structure, Genome, OMIM
IUBMB Enzyme Nomenclature
PROSITE Database of protein families and domains
InterPro (database of protein families, domains and functional sites)