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Information on EC 1.14.11.32 - codeine 3-O-demethylase
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1.14.11.32 codeine 3-O-demethylaseIUBMB Comments
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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Word Map
- 1.14.11.32
- morphine
- thebaine
-
opium
- poppy
- alkaloids
- somniferum
-
papaver
-
o-demethylation
-
virus-induced
-
analgesics
-
benzylisoquinoline
- dioxygenases
-
morphinans
- codeinone
-
narcotic
- acinetobacter
-
opiate
- salutaridine
The enzyme appears in viruses and cellular organisms
Synonyms
codeine o-demethylase, codeine-o-demethylase, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CODM
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
codeine + 2-oxoglutarate + O2 = morphine + formaldehyde + succinate + CO2
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
MetaCyc
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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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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
(R,S)-tetrahydropalmatine + 2-oxoglutarate + O2
?
-
a protoberberine, O-demethylation, 16.6% of activity with protopine
-
?
(S)-isocorydine + 2-oxoglutarate + O2
?
-
a aporphine, O-demethylation, 6.1% of activity with protopine
-
?
(S)-reticuline + 2-oxoglutarate + O2
?
-
a 1-benzylisoquinoline, O-demethylation, 16.2% of activity with protopine
-
?
(S)-scoulerine + 2-oxoglutarate + O2
?
-
a 1-benzylisoquinoline, O-demethylation, 70.4% of activity with protopine
-
?
allocryptopine + 2-oxoglutarate + O2
?
-
a protopine, O-demethylation, 50.1% of activity with protopine
-
?
cryptopine + 2-oxoglutarate + O2
?
-
a protopine, O-demethylation, 37.7% of activity with protopine
-
?
neopine + 2-oxoglutarate + O2
neomorphine + formaldehyde + succinate + CO2
-
-
-
?
O-demethylcryptopine + 2-oxoglutarate + O2
?
-
a protopine, O-demethylation, 40.8% of activity with protopine
-
?
scoulerine + 2-oxoglutarate + O2
3-O-demethylscoulerine + formaldehyde + succinate + CO2
-
120% of the activity with codeine
-
?
thebaine + 2-oxoglutarate + O2
?
-
a morphinan, O-demethylation, 80.5% of activity with protopine
-
?
additional information
?
-
-
no activity with (S)-reticuline, papaverine, (S)-corytuberine, pavine, salutaridine, oripavine, noscapine
-
?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
-
-
-
?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
-
-
-
?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
-
alkyl hydroxylation proceeds through a radical mechanism involving an iron-oxo intermediate, followed by the elimination of formaldehyde
-
?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
-
a morphinan, O-demethylation, 89.8% of activity with protopine
-
?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
-
-
-
?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
-
-
-
?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
-
25% of the activity with codeine. Alkyl hydroxylation proceeds through a radical mechanism involving an iron-oxo intermediate, followed by the elimination of formaldehyde
-
?
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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
neopine + 2-oxoglutarate + O2
neomorphine + formaldehyde + succinate + CO2
-
-
-
-
?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
-
-
-
-
?
codeine + 2-oxoglutarate + O2
morphine + formaldehyde + succinate + CO2
-
-
-
-
?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
-
-
-
-
?
thebaine + 2-oxoglutarate + O2
oripavine + formaldehyde + succinate + CO2
-
-
-
-
?
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
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
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
high-morphine varieties (i.e. L, 11 and 40) and a mutant variety (i.e. T) that accumulates high levels of thebaine and oripavine, but lacks morphine and codeine
-
-
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
the enzyme belongs to the 2-oxoglutarate/Fe(II)-dependent dioxygenase superfamily
malfunction
-
virus-induced gene silencing of CODM in opium poppy efficiently blocks metabolism at codeine
metabolism
physiological function
-
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
metabolism
-
codeine O-demethylase catalyzes the last step of morphine biosynthesis in opium poppy
metabolism
-
the enzyme is involved in the morphinan pathway via codeine of the biosynthesis of benzylisoquinoline alkaloids in Papaver somniferum, overview
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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). DIOX3_PAPSO
360
0
40849
Swiss-Prot
other Location (Reliability: 4)
A0A072UU33_MEDTR
360
0
40989
TrEMBL
other Location (Reliability: 4)
A0A2P6RIN4_ROSCH
354
0
40543
TrEMBL
other Location (Reliability: 2)
A0A2P6R9Y2_ROSCH
175
0
19737
TrEMBL
other Location (Reliability: 4)
A0A2P6RIL1_ROSCH
341
0
38324
TrEMBL
other Location (Reliability: 2)
A0A2P6R9W9_ROSCH
290
0
33298
TrEMBL
Secretory Pathway (Reliability: 5)
A0A2P6RIL7_ROSCH
353
0
40555
TrEMBL
other Location (Reliability: 2)
A0A396GUN9_MEDTR
293
0
33168
TrEMBL
other Location (Reliability: 2)
A0A396H077_MEDTR
314
0
36225
TrEMBL
other Location (Reliability: 3)
G7K0H8_MEDTR
354
0
40463
TrEMBL
other Location (Reliability: 5)
A0A072TFU2_MEDTR
352
0
40005
TrEMBL
other Location (Reliability: 3)
A0A2P6RVA1_ROSCH
367
0
41296
TrEMBL
other Location (Reliability: 4)
A0A2P6RIL2_ROSCH
353
0
40443
TrEMBL
other Location (Reliability: 2)
A0A2G9GFI2_9LAMI
341
0
39194
TrEMBL
other Location (Reliability: 2)
A0A396HR89_MEDTR
353
0
39929
TrEMBL
other Location (Reliability: 3)
A0A396HT65_MEDTR
106
0
11947
TrEMBL
other Location (Reliability: 3)
A0A396GP86_MEDTR
183
0
21146
TrEMBL
other Location (Reliability: 5)
A0A072TR49_MEDTR
362
0
41394
TrEMBL
other Location (Reliability: 3)
A0A072TK27_MEDTR
150
0
16718
TrEMBL
other Location (Reliability: 2)
G7J7S5_MEDTR
354
0
40619
TrEMBL
other Location (Reliability: 2)
A0A2P6RIK1_ROSCH
346
0
39042
TrEMBL
other Location (Reliability: 2)
A0A2G9GVC4_9LAMI
337
0
38990
TrEMBL
Mitochondrion (Reliability: 4)
G7K0G3_MEDTR
354
0
40291
TrEMBL
other Location (Reliability: 4)
G7K0G4_MEDTR
355
0
40764
TrEMBL
other Location (Reliability: 4)
A0A396JEV8_MEDTR
377
0
43619
TrEMBL
other Location (Reliability: 3)
A0A2I6ZMT0_PAPSO
324
0
36931
TrEMBL
other Location (Reliability: 2)
A0A2P6RVA3_ROSCH
358
0
40576
TrEMBL
other Location (Reliability: 3)
A0A072V5M6_MEDTR
363
0
41631
TrEMBL
Chloroplast (Reliability: 5)
A0A072UPY1_MEDTR
358
0
40978
TrEMBL
other Location (Reliability: 3)
A0A2P6Q577_ROSCH
364
0
41783
TrEMBL
other Location (Reliability: 5)
A0A2P6Q9I8_ROSCH
261
0
29691
TrEMBL
other Location (Reliability: 2)
A0A072TJC7_MEDTR
166
0
19175
TrEMBL
other Location (Reliability: 3)
A0A2P6QY58_ROSCH
370
0
41787
TrEMBL
other Location (Reliability: 5)
A0A2G9HXH4_9LAMI
352
0
40457
TrEMBL
other Location (Reliability: 2)
A0A396HT84_MEDTR
359
0
40748
TrEMBL
other Location (Reliability: 2)
A0A2P6Q8S8_ROSCH
299
0
34064
TrEMBL
other Location (Reliability: 5)
A0A2G9H8K2_9LAMI
352
0
39705
TrEMBL
other Location (Reliability: 3)
A0A2G9GGS2_9LAMI
356
0
39681
TrEMBL
other Location (Reliability: 3)
A0A2G9HA08_9LAMI
354
0
40184
TrEMBL
other Location (Reliability: 4)
A0A072UES1_MEDTR
354
0
40453
TrEMBL
other Location (Reliability: 4)
G7L9H5_MEDTR
354
0
41002
TrEMBL
other Location (Reliability: 3)
A0A072U0L2_MEDTR
358
0
41147
TrEMBL
other Location (Reliability: 5)
A0A2P6Q9I6_ROSCH
375
0
42638
TrEMBL
other Location (Reliability: 3)
A0A2P6PL48_ROSCH
381
0
42776
TrEMBL
other Location (Reliability: 3)
A0A2G9HYM0_9LAMI
341
0
39194
TrEMBL
other Location (Reliability: 2)
A0A2G9G059_9LAMI
341
0
39205
TrEMBL
other Location (Reliability: 2)
A0A396JCL4_MEDTR
354
0
40629
TrEMBL
other Location (Reliability: 3)
A0A396GU58_MEDTR
170
0
19707
TrEMBL
other Location (Reliability: 5)
A0A2P6RIJ9_ROSCH
364
0
40966
TrEMBL
other Location (Reliability: 2)
A0A2G9GFJ6_9LAMI
352
0
39696
TrEMBL
other Location (Reliability: 3)
A0A2G9HA10_9LAMI
354
0
40262
TrEMBL
other Location (Reliability: 3)
A0A2P6RIL8_ROSCH
265
0
31182
TrEMBL
other Location (Reliability: 2)
A0A396GQ72_MEDTR
61
0
6881
TrEMBL
other Location (Reliability: 4)
A0A2P6R9X0_ROSCH
354
0
40134
TrEMBL
other Location (Reliability: 3)
A0A2G9HKH6_9LAMI
361
0
41441
TrEMBL
other Location (Reliability: 3)
A0A396GMF6_MEDTR
355
0
40501
TrEMBL
other Location (Reliability: 4)
A0A072UPY7_MEDTR
353
0
40235
TrEMBL
other Location (Reliability: 2)
G7L9H8_MEDTR
354
0
40882
TrEMBL
other Location (Reliability: 3)
G7JGK5_MEDTR
351
0
39816
TrEMBL
other Location (Reliability: 2)
A0A2I6ZMT5_PAPSO
324
0
36965
TrEMBL
other Location (Reliability: 2)
A0A2P6R9X5_ROSCH
374
0
42690
TrEMBL
Chloroplast (Reliability: 5)
A0A396J9I4_MEDTR
83
0
9648
TrEMBL
other Location (Reliability: 3)
A0A072TZX2_MEDTR
363
0
42114
TrEMBL
other Location (Reliability: 4)
A0A2P6R9W8_ROSCH
355
0
40078
TrEMBL
other Location (Reliability: 3)
A0A2G9H8N3_9LAMI
77
0
8499
TrEMBL
other Location (Reliability: 5)
A0A072V311_MEDTR
353
0
40552
TrEMBL
other Location (Reliability: 3)
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
E338G/I340L/L341V/K342E
-
site-directed mutagenesis, the mutant exhibits demethylase activity exclusively toward codeine, not also toward thebaine like the wild-type enzyme
R334S/R336S
-
site-directed mutagenesis, the mutant retains O-demethylase activity toward either thebaine or codeine like the wild-type enzyme
R334S/R336T
-
site-directed mutagenesis, the mutant retains O-demethylase activity toward either thebaine or codeine like the wild-type enzyme
S149M/L151F/S152T
-
site-directed mutagenesis, the mutant is expressed at low levels, perhaps due to improper folding
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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
expression of His-tagged wild-type enzyme and mutants in Escherichia coli strain SG13009
-
phylogenetic tree, CODM real time quantitative PCR expression analysis, recombinant expression
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is significantly up-regulated with methyl jasmonate and salicylic acid treatments at 48 h
-
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REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hagel, J.M.; Facchini, P.J.
Dioxygenases catalyze the O-demethylation steps of morphine biosynthesis in opium poppy.
Nat. Chem. Biol.
6
273-275
2010
Papaver somniferum
brenda
Runguphan, W.; Glenn, W.S.; OConnor, S.E.
Redesign of a dioxygenase in morphine biosynthesis
Chem. Biol.
19
674-678
2012
Papaver somniferum
brenda
Farrow, S.C.; Facchini, P.J.
Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy
J. Biol. Chem.
288
28997-29012
2013
Papaver somniferum
brenda
Hashemi, S.; Naghavi, M.
Production and gene expression of morphinan alkaloids in hairy root culture of Papaver orientale L. using abiotic elicitors
Plant Cell
125
31-41
2016
Papaver orientale
-
brenda
Pandey, S.S.; Singh, S.; Babu, C.S.; Shanker, K.; Srivastava, N.K.; Kalra, A.
Endophytes of opium poppy differentially modulate host plant productivity and genes for the biosynthetic pathway of benzylisoquinoline alkaloids
Planta
243
1097-1114
2016
Papaver somniferum
brenda
Fossati, E.; Narcross, L.; Ekins, A.; Falgueyret, J.P.; Martin, V.J.
Synthesis of morphinan alkaloids in Saccharomyces cerevisiae
PLoS ONE
10
e0124459
2015
Papaver somniferum
brenda
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