BRENDA home
History
Information on EC 1.14.11.32 - codeine 3-O-demethylase
for references in articles please use BRENDA:EC1.14.11.32Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
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.
Specify your search results
Word Map
- 1.14.11.32
- thebaine
- morphine
- poppy
-
opium
-
papaver
- somniferum
-
o-demethylation
-
benzylisoquinoline
-
virus-induced
- codeinone
-
morphinans
-
analgesics
- dioxygenases
- acinetobacter
-
narcotic
- salutaridinol
-
opiate
The enzyme appears in viruses and cellular organisms
Synonyms
codeine O-demethylase, codeine-O-demethylase, CODM, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CODM
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
codeine + 2-oxoglutarate + O2 = morphine + formaldehyde + succinate + CO2
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
MetaCyc
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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)
A0A072TR49_MEDTR
362
0
41394
TrEMBL
other Location (Reliability: 3)
A0A072UPY1_MEDTR
358
0
40978
TrEMBL
other Location (Reliability: 3)
A0A7C9AXV4_OPUST
352
0
40334
TrEMBL
other Location (Reliability: 1)
A0A2P6R9Y2_ROSCH
175
0
19737
TrEMBL
other Location (Reliability: 4)
A0A396JCL4_MEDTR
354
0
40629
TrEMBL
other Location (Reliability: 3)
A0A7C9DIV5_OPUST
161
0
18095
TrEMBL
other Location (Reliability: 2)
A0A072V5M6_MEDTR
363
0
41631
TrEMBL
Chloroplast (Reliability: 5)
A0A2P6RVA1_ROSCH
367
0
41296
TrEMBL
other Location (Reliability: 4)
A0A2G9GVC4_9LAMI
337
0
38990
TrEMBL
Mitochondrion (Reliability: 4)
A0A2G9HA10_9LAMI
354
0
40262
TrEMBL
other Location (Reliability: 3)
A0A7C8ZX81_OPUST
168
0
19207
TrEMBL
other Location (Reliability: 2)
G7K0G4_MEDTR
355
0
40764
TrEMBL
other Location (Reliability: 4)
A0A072UPY7_MEDTR
353
0
40235
TrEMBL
other Location (Reliability: 2)
A0A2P6RIL2_ROSCH
353
0
40443
TrEMBL
other Location (Reliability: 2)
A0A2P6Q9I8_ROSCH
261
0
29691
TrEMBL
other Location (Reliability: 2)
A0A2P6R9X5_ROSCH
374
0
42690
TrEMBL
Chloroplast (Reliability: 5)
G7J7S5_MEDTR
354
0
40619
TrEMBL
other Location (Reliability: 2)
A0A2P6RIN4_ROSCH
354
0
40543
TrEMBL
other Location (Reliability: 2)
A0A396GQ72_MEDTR
61
0
6881
TrEMBL
other Location (Reliability: 4)
A0A396GU58_MEDTR
170
0
19707
TrEMBL
other Location (Reliability: 5)
G7L9H8_MEDTR
354
0
40882
TrEMBL
other Location (Reliability: 3)
A0A072V311_MEDTR
353
0
40552
TrEMBL
other Location (Reliability: 3)
A0A072TK27_MEDTR
150
0
16718
TrEMBL
other Location (Reliability: 2)
A0A2P6Q577_ROSCH
364
0
41783
TrEMBL
other Location (Reliability: 5)
A0A396HR89_MEDTR
353
0
39929
TrEMBL
other Location (Reliability: 3)
A0A7C9B1H2_OPUST
225
0
26095
TrEMBL
other Location (Reliability: 1)
A0A7C8YK28_OPUST
373
0
42414
TrEMBL
other Location (Reliability: 3)
G7L9H5_MEDTR
354
0
41002
TrEMBL
other Location (Reliability: 3)
A0A2P6RIJ9_ROSCH
364
0
40966
TrEMBL
other Location (Reliability: 2)
A0A2G9HA08_9LAMI
354
0
40184
TrEMBL
other Location (Reliability: 4)
A0A2G9H8K2_9LAMI
352
0
39705
TrEMBL
other Location (Reliability: 3)
A0A2I6ZMT5_PAPSO
324
0
36965
TrEMBL
other Location (Reliability: 2)
A0A2P6R9W8_ROSCH
355
0
40078
TrEMBL
other Location (Reliability: 3)
A0A2P6R9W9_ROSCH
290
0
33298
TrEMBL
Secretory Pathway (Reliability: 5)
A0A2P6Q8S8_ROSCH
299
0
34064
TrEMBL
other Location (Reliability: 5)
A0A2P6R9X0_ROSCH
354
0
40134
TrEMBL
other Location (Reliability: 3)
A0A2G9HXH4_9LAMI
352
0
40457
TrEMBL
other Location (Reliability: 2)
A0A396HT65_MEDTR
106
0
11947
TrEMBL
other Location (Reliability: 3)
A0A072TJC7_MEDTR
166
0
19175
TrEMBL
other Location (Reliability: 3)
A0A2I6ZMT0_PAPSO
324
0
36931
TrEMBL
other Location (Reliability: 2)
A0A2G9H8N3_9LAMI
77
0
8499
TrEMBL
other Location (Reliability: 5)
A0A2G9HYM0_9LAMI
341
0
39194
TrEMBL
other Location (Reliability: 2)
A0A7C8ZZ57_OPUST
356
0
40527
TrEMBL
other Location (Reliability: 2)
A0A7C9DTY3_OPUST
124
0
14226
TrEMBL
other Location (Reliability: 2)
G7K0H8_MEDTR
354
0
40463
TrEMBL
other Location (Reliability: 5)
A0A2G9G059_9LAMI
341
0
39205
TrEMBL
other Location (Reliability: 2)
A0A396JEV8_MEDTR
377
0
43619
TrEMBL
other Location (Reliability: 3)
A0A396H077_MEDTR
314
0
36225
TrEMBL
other Location (Reliability: 3)
A0A7C9DIW4_OPUST
291
0
33205
TrEMBL
Mitochondrion (Reliability: 4)
A0A072U0L2_MEDTR
358
0
41147
TrEMBL
other Location (Reliability: 5)
A0A2P6PL48_ROSCH
381
0
42776
TrEMBL
other Location (Reliability: 3)
A0A2G9GGS2_9LAMI
356
0
39681
TrEMBL
other Location (Reliability: 3)
A0A7C9CU88_OPUST
150
0
16749
TrEMBL
Mitochondrion (Reliability: 5)
A0A7C8ZYY5_OPUST
174
0
19883
TrEMBL
other Location (Reliability: 2)
A0A7C8YZ01_OPUST
368
0
41210
TrEMBL
other Location (Reliability: 2)
A0A2P6RVA3_ROSCH
358
0
40576
TrEMBL
other Location (Reliability: 3)
A0A2G9GFI2_9LAMI
341
0
39194
TrEMBL
other Location (Reliability: 2)
A0A2G9GFJ6_9LAMI
352
0
39696
TrEMBL
other Location (Reliability: 3)
A0A072UES1_MEDTR
354
0
40453
TrEMBL
other Location (Reliability: 4)
A0A396GUN9_MEDTR
293
0
33168
TrEMBL
other Location (Reliability: 2)
A0A072TFU2_MEDTR
352
0
40005
TrEMBL
other Location (Reliability: 3)
A0A2P6QY58_ROSCH
370
0
41787
TrEMBL
other Location (Reliability: 5)
A0A2P6RIL1_ROSCH
341
0
38324
TrEMBL
other Location (Reliability: 2)
A0A2P6RIL7_ROSCH
353
0
40555
TrEMBL
other Location (Reliability: 2)
A0A7C9DE23_OPUST
162
0
18233
TrEMBL
other Location (Reliability: 2)
A0A2P6RIL8_ROSCH
265
0
31182
TrEMBL
other Location (Reliability: 2)
A0A2P6RIK1_ROSCH
346
0
39042
TrEMBL
other Location (Reliability: 2)
A0A396GP86_MEDTR
183
0
21146
TrEMBL
other Location (Reliability: 5)
A0A072TZX2_MEDTR
363
0
42114
TrEMBL
other Location (Reliability: 4)
A0A396HT84_MEDTR
359
0
40748
TrEMBL
other Location (Reliability: 2)
A0A2G9HKH6_9LAMI
361
0
41441
TrEMBL
other Location (Reliability: 3)
A0A396J9I4_MEDTR
83
0
9648
TrEMBL
other Location (Reliability: 3)
G7K0G3_MEDTR
354
0
40291
TrEMBL
other Location (Reliability: 4)
G7JGK5_MEDTR
351
0
39816
TrEMBL
other Location (Reliability: 2)
A0A072UU33_MEDTR
360
0
40989
TrEMBL
other Location (Reliability: 4)
A0A2P6Q9I6_ROSCH
375
0
42638
TrEMBL
other Location (Reliability: 3)
A0A396GMF6_MEDTR
355
0
40501
TrEMBL
other Location (Reliability: 4)
A0A7C9FR40_OPUST
342
0
38903
TrEMBL
other Location (Reliability: 3)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged wild-type enzyme and mutants from Escherichia coli strain SG13009 by cobalt affinity chromatography
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is significantly up-regulated with methyl jasmonate and salicylic acid treatments at 48 h
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
Select items on the left to see more content.
EXTERNAL LINKS (specific for EC-Number 1.14.11.32)
html completed
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
About BRENDA
Help
Download
Contribution
member of
curated at
curated at
Server: brenda4 Ver: 9edf756-main (2022-05-17 10:30:03 +0200)