KEGG   PATHWAY: ko00950
Entry
ko00950                     Pathway                                

Name
Isoquinoline alkaloid biosynthesis
Description
Isoquinoline alkaloids are tyrosine-derived plant alkaloids with an isoquinoline skeleton. Among them benzylisoquinoline alkaloids form an important group with potent pharmacological activity, including analgesic compounds of morphine and codeine, and anti-infective agents of berberine, palmatine, and magnoflorine. Biosynthesis of isoquinoline alkaloids proceeds via decarboxylation of tyrosine or DOPA to yield dopamine, which together with 4-hydroxyphenylacetaldehyde, an aldehyde derived from tyrosine, is converted to reticuline, an important precursor of various benzylisoquinoline alkaloids.
Class
Metabolism; Biosynthesis of other secondary metabolites
Pathway map
ko00950  Isoquinoline alkaloid biosynthesis
ko00950

Other DBs
GO: 0033075
Orthology
K03334  L-amino-acid oxidase [EC:1.4.3.2]
K14454  aspartate aminotransferase, cytoplasmic [EC:2.6.1.1]
K14455  aspartate aminotransferase, mitochondrial [EC:2.6.1.1]
K00811  aspartate aminotransferase, chloroplastic [EC:2.6.1.1]
K00812  aspartate aminotransferase [EC:2.6.1.1]
K00813  aspartate aminotransferase [EC:2.6.1.1]
K11358  aspartate aminotransferase [EC:2.6.1.1]
K15849  bifunctional aspartate aminotransferase and glutamate/aspartate-prephenate aminotransferase [EC:2.6.1.1 2.6.1.78 2.6.1.79]
K00815  tyrosine aminotransferase [EC:2.6.1.5]
K00832  aromatic-amino-acid transaminase [EC:2.6.1.57]
K00838  aromatic amino acid aminotransferase I / 2-aminoadipate transaminase [EC:2.6.1.57 2.6.1.39 2.6.1.27 2.6.1.5]
K22327  4-hydroxyphenylacetaldehyde synthase [EC:4.1.1.108]
K13382  (S)-norcoclaurine synthase [EC:4.2.1.78]
K13383  (RS)-norcoclaurine 6-O-methyltransferase [EC:2.1.1.128]
K13384  (RS)-1-benzyl-1,2,3,4-tetrahydroisoquinoline N-methyltransferase [EC:2.1.1.115 2.1.1.140]
K13385  N-methylcoclaurine 3'-monooxygenase [EC:1.14.14.102]
K13386  3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase [EC:2.1.1.116]
K22088  norreticuline-7-O-methyltransferase [EC:2.1.1.-]
K22089  tetrahydroprotoberberine oxidase [EC:1.3.3.8]
K13387  berbamunine synthase [EC:1.14.19.66]
K00422  polyphenol oxidase [EC:1.10.3.1]
K00501  tyrosine 3-monooxygenase [EC:1.14.16.2]
K00505  tyrosinase [EC:1.14.18.1]
K01592  tyrosine decarboxylase [EC:4.1.1.25]
K01593  aromatic-L-amino-acid/L-tryptophan decarboxylase [EC:4.1.1.28 4.1.1.105]
K22090  noroxomaritidine/norcraugsodine reductase [EC:1.3.1.- 1.4.1.-]
K21311  norbelladine O-methyltransferase [EC:2.1.1.336]
K21208  noroxomaritidine synthase [EC:1.14.19.50 1.14.19.-]
K00274  monoamine oxidase [EC:1.4.3.4]
K00276  primary-amine oxidase [EC:1.4.3.21]
K13371  aralkylamine dehydrogenase light chain [EC:1.4.9.2]
K13372  aralkylamine dehydrogenase heavy chain [EC:1.4.9.2]
K22091  O-methyltransferase [EC:2.1.1.-]
K22092  beta-glucosidase [EC:3.2.1.-]
K13389  (S)-corytuberine synthase [EC:1.14.19.51]
K21580  reticuline N-methyltransferase [EC:2.1.1.337]
K13390  (R,S)-reticuline 7-O-methyltransferase [EC:2.1.1.291]
K22093  1,2-dehydroreticuline synthase/reductase [EC:1.14.19.54 1.5.1.27]
K13391  salutaridine synthase [EC:1.14.19.67]
K13392  salutaridine reductase (NADPH) [EC:1.1.1.248]
K13393  salutaridinol 7-O-acetyltransferase [EC:2.3.1.150]
K01742  thebaine synthase [EC:4.2.99.24]
K14975  codeine 3-O-demethylase [EC:1.14.11.32]
K14976  thebaine 6-O-demethylase [EC:1.14.11.31]
K03378  morphine 6-dehydrogenase [EC:1.1.1.218]
K13394  codeinone reductase [EC:1.1.1.247]
K00307  reticuline oxidase [EC:1.21.3.3]
K21070  (S)-cheilanthifoline synthase [EC:1.14.19.65]
K13395  (S)-stylopine/(S)-canadine/(S)-nandinine synthase [EC:1.14.19.64 1.14.19.68 1.14.19.73]
K13396  (S)-tetrahydroprotoberberine N-methyltransferase [EC:2.1.1.122]
K20621  (S)-N-methylcanadine 1-hydroxylase [EC:1.14.14.166]
K22094  (S)-1-hydroxy-N-methylcanadine 13-hydroxylase [EC:1.14.14.163]
K22095  (13S,14R)-1,13-dihydroxy-N-methylcandine 13-O-acetyltransferase [EC:2.3.1.285]
K22096  (13S,14R)-13-O-acetyl-1-hydroxy-N-methylcanadine 8-hydroxylase [EC:1.14.14.167]
K22097  3-O-acetylpapaveroxine carboxylesterase [EC:3.1.1.105]
K22098  noscapine synthase [EC:1.1.1.415]
K23157  3-O-acetyl-4'-O-demethylpapaveroxine 4'-O-methyltransferase subunit OMT2 [EC:2.1.1.352]
K23158  3-O-acetyl-4'-O-demethylpapaveroxine 4'-O-methyltransferase subunit OMT3
K21692  methyltetrahydroprotoberberine 14-monooxygenase [EC:1.14.14.97]
K21693  protopine 6-monooxygenase [EC:1.14.14.98]
K13397  (S)-scoulerine 9-O-methyltransferase [EC:2.1.1.117]
K13398  columbamine O-methyltransferase [EC:2.1.1.118]
Compound
C00082  L-Tyrosine
C00355  3,4-Dihydroxy-L-phenylalanine
C00483  Tyramine
C00757  Berberine
C00811  4-Coumarate
C01179  3-(4-Hydroxyphenyl)pyruvate
C01516  Morphine
C01735  Morphinone
C01795  Columbamine
C01852  Secologanin
C02105  (S)-Reticuline
C02106  (S)-Scoulerine
C02134  Allocryptopine
C02890  Tetrahydropalmatine
C02915  (S)-N-Methylcanadine
C02916  (S)-Norlaudanosoline
C03329  (S)-Canadine
C03758  Dopamine
C03765  4-Hydroxyphenylacetaldehyde
C04043  3,4-Dihydroxyphenylacetaldehyde
C04118  Isocorypalmine
C05174  (S)-Cheilanthifoline
C05175  Stylopine
C05176  (S)-N-Methylcoclaurine
C05177  Berbamunine
C05178  (R)-Reticuline
C05179  Salutaridine
C05189  Protopine
C05190  6-Hydroxyprotopine
C05191  Dihydrosanguinarine
C05193  12-Hydroxydihydrochelirubine
C05194  Dihydrochelirubine
C05202  3'-Hydroxy-N-methyl-(S)-coclaurine
C05220  Salutaridinol
C05243  (R)-N-Methylcoclaurine
C05247  10-Hydroxydihydrosanguinarine
C05315  Palmatine
C05316  Dihydromacarpine
C05322  7-O-Acetylsalutaridinol
C06160  (S)-Norcoclaurine
C06161  (S)-Coclaurine
C06162  Sanguinarine
C06163  (S)-cis-N-Methylstylopine
C06165  Macarpine
C06167  1,2-Dehydroreticuline
C06171  Codeinone
C06172  Neopinone
C06173  Thebaine
C06174  Codeine
C06175  Oripavine
C06327  Chelirubine
C06511  Guattegaumerine
C06512  2'-Norberbamunine
C06516  (R)-Norreticuline
C06517  (S)-6-O-Methylnorlaudanosoline
C06518  (S)-Nororientaline
C06520  (S)-Norreticuline
C06533  Papaverine
C07304  Deacetylisoipecoside
C07307  Deacetylipecoside
C07592  Colchicine
C08521  Caranine
C08526  Galanthamine
C08527  Haemanthamine
C08532  Lycorine
C09248  Tubulosine
C09328  Alangimarckine
C09330  Alangiside
C09337  Ankorine
C09390  Cephaeline
C09421  Emetine
C09581  Magnoflorine
C09592  alpha-Narcotine
C09593  Narcotoline
C11250  Demecolcine
C11813  Demethylalangiside
C11814  Demethylisoalangiside
C11815  Isoalangiside
C11816  Protoemetine
C11817  Deoxytubulosine
C11818  (R)-Canadine
C12162  Crinine
C12173  Norgalanthamine
C12180  (-)-8-Demethylmaritidine
C12193  Vittatine
C15530  Corydaline
C16700  3,4-Dihydroxybenzaldehyde
C16701  Norbelladine
C16702  4'-O-Methylnorbelladine
C16703  N-Demethylnarwedine
C16706  4-Hydroxydihydrocinnamaldehyde
C16707  (S)-Autumnaline
C16708  Isoandrocymbine
C16709  O-Methylandrocymbine
C16710  N-Formyldemecolcine
C16712  Deacetylcolchicine
C16713  Floramultine
C16714  Kreysigine
C17591  (S)-Corytuberine
C17592  Laudanine
C20297  Narcotine hemiacetal
C20299  Papaveroxine
C21405  (4aS,10bR)-Noroxomaritidine
C21406  (4aR,10bS)-Noroxomaritidine
C21566  6-O-Methyldeacetylisoipecoside
C21583  6-O-Methyl-N-deacetylisoipecoside aglycon
C21584  7'-O-Dmethylcephaeline
C21586  (S)-1-Hydroxy-N-methylcanadine
C21587  (13S,14R)-1,13-Dihydroxy-N-methylcanadine
C21588  (13S,14R)-1-Hydroxy-13-O-acetyl-N-methylcanadine
C21589  (13S,14R)-1,8-Dihydroxy-13-O-acetyl-N-methylcanadine
C21590  4'-O-Desmethyl-3-O-acetylpapaveroxine
C21591  3-O-Acetylpapaveroxine
C21599  4'-O-Desmethylpapaveroxine
C21600  Narcotoline hemiacetal
C21630  (S)-Norlaudanine
C21631  (S)-Tetrahydropapaverine
C21633  Noroxopluviine
C21634  Norcraugsodine
C21635  (4aR,10bS)-Normaritidine
C21637  Elwesine
C21639  Maritinamine
Reference
  Authors
Morishige T, Tsujita T, Yamada Y, Sato F
  Title
Molecular characterization of the S-adenosyl-L-methionine:3'-hydroxy-N-methylcoclaurine 4'-O-methyltransferase involved in isoquinoline alkaloid biosynthesis in Coptis japonica.
  Journal
J Biol Chem 275:23398-405 (2000)
DOI:10.1074/jbc.M002439200
Reference
  Authors
Morishige T, Dubouzet E, Choi KB, Yazaki K, Sato F
  Title
Molecular cloning of columbamine O-methyltransferase from cultured Coptis japonica cells.
  Journal
Eur J Biochem 269:5659-67 (2002)
DOI:10.1046/j.1432-1033.2002.03275.x
Reference
  Authors
Ounaroon A, Decker G, Schmidt J, Lottspeich F, Kutchan TM
  Title
(R,S)-Reticuline 7-O-methyltransferase and (R,S)-norcoclaurine 6-O-methyltransferase of Papaver somniferum - cDNA cloning and characterization of methyl transfer enzymes of alkaloid biosynthesis in opium poppy.
  Journal
Plant J 36:808-19 (2003)
DOI:10.1046/j.1365-313X.2003.01928.x
Reference
  Authors
Ikezawa N, Iwasa K, Sato F
  Title
Molecular cloning and characterization of CYP80G2, a cytochrome P450 that catalyzes an intramolecular C-C phenol coupling of (S)-reticuline in magnoflorine biosynthesis, from cultured Coptis japonica cells.
  Journal
J Biol Chem 283:8810-21 (2008)
DOI:10.1074/jbc.M705082200
Reference
  Authors
Facchini PJ, De Luca V
  Title
Opium poppy and Madagascar periwinkle: model non-model systems to investigate alkaloid biosynthesis in plants.
  Journal
Plant J 54:763-84 (2008)
DOI:10.1111/j.1365-313X.2008.03438.x
Reference
  Authors
Minami H, Kim JS, Ikezawa N, Takemura T, Katayama T, Kumagai H, Sato F
  Title
Microbial production of plant benzylisoquinoline alkaloids.
  Journal
Proc Natl Acad Sci U S A 105:7393-8 (2008)
DOI:10.1073/pnas.0802981105
Reference
  Authors
Rueffer M, Bauer W, Zenk MH.
  Title
The formation of corydaline and related alkaloids in Corydalis cava in vivo and in vitro.
  Journal
Can J Chem 72:170-175 (1994)
DOI:10.1139/v94-026
Reference
  Authors
Sekine Y, Crevelling C, Bell M, Brossi A.
  Title
Mammalian alkaloids: O-methylation of (+-)-norcoclaurine-1-carboxylic acid and related isoquinolines including (S)- and (R)-norcoclaurine with 14C-labeled S-adenosyl-L-methionine in presence of mammalian catechol O-methyltransferase.
  Journal
Helv Chim Acta 73:426-432 (1990)
DOI:10.1002/hlca.19900730222
Reference
  Authors
De-Eknamkul W, Tanahashi T, Zenk MH.
  Title
Enzymic 10-hydroxylation and 10-O-methylation of dihydrosanguinarine in dihydrochelirubine formation by Eschscholtzia.
  Journal
Phytochemistry 31:2713-2717 (1992)
DOI:10.1016/0031-9422(92)83617-8
Reference
  Authors
Kammerer L, De-Eknamkul W, Zenk MH.
  Title
Enzymic 12-hydroxylation and 12-O-methylation of dihydrochelirubine in dihydromacarpine formation by Thalictrum bulgaricum.
  Journal
Phytochemistry 36:1409-1416 (1994)
DOI:10.1016/S0031-9422(00)89732-0
Reference
  Authors
Schumacher HM, Zenk MH
  Title
Partial purification and characterization of dihydrobenzophenanthridine oxidase from Eschscholtzia californica cell suspension cultures.
  Journal
Plant Cell Rep 7:43-6 (1988)
DOI:10.1007/BF00272975
Reference
  Authors
Rueffer M, Zenk MH.
  Title
Enzymatic formation of protopines by a microsomal cytochrome P-450 system of Corydalis vaginans.
  Journal
Tetrahedron Lett 28:5307-5310 (1987)
DOI:10.1016/S0040-4039(00)96715-7
Related
pathway
ko00350  Tyrosine metabolism
ko00360  Phenylalanine metabolism
ko00400  Phenylalanine, tyrosine and tryptophan biosynthesis
ko00902  Monoterpenoid biosynthesis
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