KEGG   PATHWAY: rn00950
Entry
rn00950                     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
rn00950  Isoquinoline alkaloid biosynthesis
rn00950

Module
M00943  Reticuline biosynthesis, dopamine + 4HPAA => (S)-reticuline [PATH:rn00950]
M00944  Morphine biosynthesis, (S)-reticuline => morphine [PATH:rn00950]
M00945  Sanguinarine biosynthesis, (S)-reticuline => sanguinarine [PATH:rn00950]
M00946  Noscapine biosynthesis, (S)-reticuline => noscapine [PATH:rn00950]
Other DBs
GO: 0033075
Reaction
R00031  1,2-benzenediol:oxygen oxidoreductase
R00044  columbamine:oxygen oxidoreductase (cyclizing)
R00729  L-tyrosine:oxygen oxidoreductase (deaminating)
R00731  L-tyrosine:oxygen oxidoreductase
R00734  L-tyrosine:2-oxoglutarate aminotransferase
R00736  L-tyrosine carboxy-lyase (tyramine-forming)
R02080  3,4-dihydroxy-L-phenylalanine carboxy-lyase
R02383  monophenol,L-dopa:oxygen oxidoreductase
R02880  (S)-tetrahydroberberine:oxigen oxidoreductase
R03341  4-hydroxyphenylpyruvate carboxy-lyase
R03591  morphine:NAD+ 6-oxidoreductase
R03592  morphine:NAD(P)+ 6-oxidoreductase
R03698  oripavine,2-oxoglutarate:oxygen oxidoreductase (6-O-demethylating)
R03721  S-adenosyl-L-methionine:columbamine O-methyltransferase
R03722  (S)-tetrahydrocolumbamine:oxigen oxidoreductase
R03831  (S)-reticuline:oxygen oxidoreductase (methylene-bridge-forming)
R03832  S-adenosyl-L-methionine:3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase
R03833  (S)-reticuline,[reduced NADPH---hemoprotein reductase]:oxygen 1,2-oxidoreductase
R03834  (S)-scoulerine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase [(S)-cheilanthifoline-forming]
R03835  S-adenosyl-L-methionine:(S)-scoclaurine 9-O-methyltransferase
R03842  (S)-cis-N-methylcanadine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (14-hydroxylating)
R04077  S-adenosyl-L-methionine:5,8,13,13a-tetrahydrocolumbamine 2-O-methyltransferase
R04084  3,4-dihydroxyphenylacetaldehyde hydro-lyase (adding dopamine)
R04300  4-(2-aminoethyl)-1,2-benzenediol:oxygen oxidoreductase(deaminating)(flavin-containing)
R04305  4-hydroxyphenylacetaldehyde hydro-lyase (adding dopamine)
R04400  (S)-tetrahydrocolumbamine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (methylenedioxy-bridge-forming)
R04690  (S)-cheilanthifoline,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (methylenedioxy-bridge-forming)
R04691  
R04692  S-adenosyl-L-methionine:(S)-coclaurine-N-methyltransferase
R04694  (S)-N-methylcoclaurine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (C-O phenol-coupling)
R04695  (R)-reticuline:NADP+ oxidoreductase
R04696  (R)-reticuline,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (C-C phenol-coupling)
R04697  salutaridinol:NADP+ 7-oxidoreductase
R04699  protopine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (6-hydroxylating)
R04700  (S)-cis-N-methylstylopine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (14-hydroxylating)
R04701  
R04702  dihydrosanguinarine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (10-hydroxylating)
R04703  dihydrosanguinarine:oxygen oxidoreductase
R04705  S-adenosyl-L-methionine:12-hydroxydihydrochelirubine 12-O-methyltransferase
R04706  dihydrochelirubine:oxygen oxidoreductase
R04707  S-adenosyl-L-methionine:10-hydroxydihydrosanguinarine 10-O-methyltransferase
R04708  dihydrochelirubine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (12-hydroxylating)
R04723  acetyl-CoA:salutaridinol 7-O-acetyltransferase
R04768  dihydromacarpine:oxygen oxidoreductase
R04769  salutaridinol 7-O-acetate acetate-lyase (thebaine forming)
R05123  S-adenosyl-L-methionine:(RS)-norcoclaurine 6-O-methyltransferase
R05124  codeine:NADP+ oxidoreductase
R05125  neopinone Delta8-Delta7-isomerase
R05126  thebaine,2-oxoglutarate:oxygen oxidoreductase (6-O-demethylating)
R05127  thebaine,2-oxoglutarate:oxygen oxidoreductase (3-O-demethylating)
R05210  (S)-coclaurine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (C-O phenol-coupling)
R05211  S-adenosyl-L-methionine:(RS)-1-benzyl-1,2,3,4-tetrahydroisoquinolie N- methyltransferase
R05212  S-adenosyl-L-methionine:3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase
R05213  S-adenosyl-L-methionine:6-O-methylnorlaudanosoline 5'-O-methyltransferase
R05214  S-adenosyl-L-methionine:(RS)-norcoclaurine 6-O-methyltransferase
R05215  (R)-N-methylcoclaurine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (C-O phenol-coupling)
R05216  S-adenosyl-L-methionine:(R)-norreticuline N- methyltransferase
R05732  (S)-N-methylcoclaurine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (3'-hydroxylating)
R05749  deacetylipecoside dopamine-lyase
R05750  deacetylisoipecoside dopamine-lyase
R05887  
R05888  
R05889  
R05890  
R05894  
R05895  
R05896  
R05897  
R07169  (R)-tetrahydroberberine:NADP+ oxidoreductase
R07212  L-tyrosine,tetrahydrobiopterin:oxygen oxidoreductase(3-hydroxylating)
R07241  S-adenosyl-L-methionine:protoberberine 13-C-methyltransferase
R08435  
R08436  
R08437  S-adenosyl-L-methionine:norbelladine O-methyltransferase
R08438  
R08439  
R08440  
R08441  S-adenosyl-L-homocysteine:norgalanthamine N-methyltransferase
R08442  
R08444  
R08445  
R08446  
R08447  
R08448  
R08449  S-adenosyl-L-methionine:isoandrocymbine O-methyltransferase
R08450  
R08451  
R08452  
R08453  
R08454  
R08455  
R08456  
R08458  
R08459  
R08460  
R08513  
R08787  S-adenosyl-L-methionine:(S)-reticuline 7-O-methyltransferase
R08788  S-adenosyl-L-methionine:(R)-reticuline 7-O-methyltransferase
R08789  S-adenosyl-L-methionine:(S)-canadine N-methyltransferase
R08790  (S)-reticuline,NADPH:oxygen oxidoreductase (C-C phenol-coupling; (S)-corytuberine-forming)
R08791  S-adenosyl-L-methionine:(S)-corytuberine N-methyltransferase
R08794  
R08795  tetrahydropalmatine:oxygen oxidoreductase
R09402  codeine,2-oxoglutarate:oxygen oxidoreductase (3-O-demethylating)
R10018  
R10020  narcotine hemiacetal:NAD+ 1-oxidoreductase
R11482  4'-O-methylnorbelladine,NADPH---hemoprotein reductase:oxygen oxidoreductase (noroxomaritidine-forming)
R11483  4'-O-methylnorbelladine,NADPH---hemoprotein reductase:oxygen oxidoreductase (noroxomaritidine-forming)
R11681  S-adenosyl-L-methionine:deacetylisoipecoside 6-O-methyltransferase
R11682  6-O-methyldeacetylisoipecoside:beta-glucosidase
R11683  
R11684  
R11685  S-adenosyl-L-methionine:7'-O-demethylcephaeline 7'-O-methyltransferase
R11686  S-adenosyl-L-methionine:cephaeline 6'-O-methyltransferase
R11687  (S)-N-methylcanadine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (1-hydroxylating)
R11688  (S)-1-hydroxy-N-methylcanadine,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (13-hydroxylating)
R11689  acetyl-CoA:(13S,14R)-1,13-dihydroxy-N-methylcanadine O-acetyltransferase
R11690  (13S,14R)-13-O-acetyl-1-hydroxy-N-methylcanadine 8-hydroxylase,[reduced NADPH---hemoprotein reductase]:oxygen oxidoreductase (8-hydroxylating)
R11691  
R11692  S-adenosyl-L-methionine:3-O-acetyl-4'-O-demethylpapaveroxine 4'-O-methyltransferase
R11693  3-O-acetylpapaveroxine acetatehydrolase
R11694  4'-O-desmethyl-3-O-acetylpapaveroxine acetatehydrolase
R11695  
R11696  narcotoline hemiacetal:NAD+ 1-oxidoreductase
R11731  S-adenosyl-L-methionine:(S)-norreticuline 7-O-methyltransferase
R11740  
R11748  (S)-tetrahydropapaverine:oxygen oxidoreductase
R11751  
R11752  
R11753  
R11754  
R11756  
R11758  
R11759  
R11760  
R11761  
R11917  L-tyrosine carboxy-lyase (oxidative-deaminating)
R12262  S-adenosyl-L-methionine:narcotoline 4'-O-methyltransferase
R13191  ipecoside glucohydrolase
R13192  
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)-cis-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
C06546  Mescaline
C07304  Deacetylisoipecoside
C07307  Deacetylipecoside
C07547  Tubocurarine
C07592  Colchicine
C08521  Caranine
C08526  Galanthamine
C08527  Haemanthamine
C08532  Lycorine
C09248  Tubulosine
C09328  Alangimarckine
C09330  Alangiside
C09337  Ankorine
C09390  Cephaeline
C09421  Emetine
C09464  Ipecoside
C09541  (S)-Isoboldine
C09581  Magnoflorine
C09592  alpha-Narcotine
C09593  Narcotoline
C09654  (+)-Tetrandrine
C11250  Demecolcine
C11813  Demethylalangiside
C11814  Demethylisoalangiside
C11815  Isoalangiside
C11816  Protoemetine
C11817  Deoxytubulosine
C11818  (R)-Canadine
C12162  Crinine
C12173  Norgalanthamine
C12180  (-)-8-Demethylmaritidine
C12193  Vittatine
C12231  Anhalamine
C15530  Corydaline
C16700  3,4-Dihydroxybenzaldehyde
C16701  Norbelladine
C16702  4'-O-Methylnorbelladine
C16703  N-Demethylnarwedine
C16704  Anhalonidine
C16705  Anhalonine
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-Demethylcephaeline
C21586  (S)-1-Hydroxy-cis-N-methylcanadine
C21587  (13S,14R)-1,13-Dihydroxy-cis-N-methylcanadine
C21588  (13S,14R)-13-O-Acetyl-1-hydroxy-cis-N-methylcanadine
C21589  (13S,14R)-13-O-Acetyl-1,8-dihydroxy-cis-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
C22694  Ipecoside aglycone
Reference
PMID:10811648
  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
PMID:12423366
  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
PMID:14675446
  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
PMID:18230623
  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
PMID:18476877
  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
PMID:18492807
  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
PMID:24241413
  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
rn00350  Tyrosine metabolism
rn00360  Phenylalanine metabolism
rn00400  Phenylalanine, tyrosine and tryptophan biosynthesis
rn00902  Monoterpenoid biosynthesis
KO pathway
ko00950   

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