Alkaloids norcoclaurine synthase

Fig. 18 Reconstructed isoquinoline alkaloid biosynthetic pathway in microbes (E. coli and S. cerevisiae) [120]. Accession numbers of the genes can be taken from Gene Bank. C3,4-DHPA-A 3,4-dihydroxyphenylacetaldehyde NCS norcoclaurine synthase 60MT 6-0-methyltransferase CNMT coclaurine-/V-mcthyltransferase 4 OMT 4 -0-methyltransferase BBE berberine bridge enzyme NMT /V-methyltransferase)...

SAMANANI, N., FACCHINI, P.J., Isolation and partial characterization of norcoclaurine synthase, the first committed step in benzylisoquinoline alkaloid biosynthesis, from opium poppy. Planta, 2001,213, 898-906. 

Samanani N, Liscombe DK, Facchini PJ. Molecular cloning and characterization of norcoclaurine synthase, an enzyme catalyzing benzyUsoquinoline alkaloid biosynthesis. Plant J. 2004 40 302-313. 

Scheme 1. Biosynthesis of the benzylisoquinoline alkaloids berberine, morphine, and sang-uinarine. Enzymes for which corresponding molecular clones have been isolated are shown in bold. Abbreviations 4 OMT, 3 -hydroxy-A-methylcoclaurine 4 -0-methyltransferase 60MT, norcoclaurine 6-0-methyltransferase 70MT, reticuline 7-0-methyltransferase BBE, berberine bridge enzyme CFS, cheilanthifoline synthase CNMT, coclaurine A-methyltransf-erase COR, codeinone reductase CYP719A1, canadine synthase CYP80A1, berbamunine synthase CYP80B1, A-methylcoclaurine 3 -hydroxylase DBOX, dihydrobenzophenanthri-dine oxidase DRR, 1,2-dehydroreticuline reductase DRS, 1,2-dehydro reticuline synthase MSH, A-methylstylopine 14-hydroxylase NCS, norcoclaurine synthase P6H,...

Luk, L. Y., et al.. Mechanistic studies on norcoclaurine synthase of benzylisoquinoline alkaloid biosynthesis an enzymatic Pictet-Spengler reaction. Biochemistry, 2007. 46(35) p. 10153-61. 

Samanani N, Facchini PJ (2002) Purification and characterization of norcoclaurine synthase. The first committed enzyme in benzylisoquinoline alkaloid biosynthesis in plants. J Biol Chem 277 33878-33883... 

Fig. 8.12 Reconstruction of benzylisoquinoline alkaloid (BIA) pathway in microorganisms. MAO bacterial monoamine oxidase from Micrococcus luteus, NCS norcoclaurine synthase from Coptis japonica, 6-OMT norcoclaurine 6-0-methyltransferase from Coptis japonica, CNMT, coclaurine-]V-melhyltransferase from Coptis japonica, 4-OMT 3 -hydroxy-iV-methylcoclaurine-4 -0-methyltransferase from Coptis Japonica, CYP80G2 plant cytochrome P450 enzymes from Coptis japonica, BBE berbeiine bridge enzyme from Coptis japonica (Adopted from Ref. [101])...

The opium poppy (Papaver somniferum L. [Papaveraceae]) latex contains benzylisoquinoline alkaloids and is a widely known source of the analgesic drugs morphine and codeine. The biosynthesis of benzylisoquinoline alkaloids begins with a condensation reaction catalyzed by norcoclaurine synthase of DA [161]. The structural features of benzylisoquinoline alkaloids derived from DA might provide some explanation for the documented affinity of some natural alkaloids of this class, and some synthetic derivatives, for DA receptors [162]. Indeed, the chemical structure of morphine has been used as a template for the development of the PD drug, apomorphine (47). Apomorphine includes a catecholaminergic moiety in its... 

At the subcellular level, the morphine biosynthetic pathway combines several cytochrome P-450 enzymes, bound to ER membranes (Chou and Kutchan, 1998) with soluble enzymes that reside in ER derived vesicles, e.g. norcoclaurine synthase, or in the cytosol, e.g. codeinone reductase (Zenk, 1994 Facchini and St-Pierre, 2005). The diverse localization of the biosynthetic enzymes requires several transport steps of the intermediates between cytosol, vesicles and vacuoles. Only one of them has been characterized by pioneering experiments (Deus-Neumann and Zenk, 1986) vacuolar vesicles prepared from Fumaria capreolata accumulate (S)-reticulin or (S)-scoulerin via highly specific transporters, that discriminate between (S)- and (R) stereoisomer and exclude other benzylisoquinolines (sanguinarine, protopine, morphine) and alkaloids of unrelated families (e.g. indoles or tropanes). Uptake is energized by the pH gradient across the tonoplast. Accumulated... 

Fig. 10.8 Selected cDNAs isolated in recent years that encode enzymes involved in the biosynthesis of various classes of isoquinoline alkaloids. 6-OMT, norcoclaurine 6-0-methyltransferase 23 CYP80A1, berbamunine synthase 19 CYP80B1, (S)-A-methylcoclaurine 3 -hydroxylase 20 CPR, cytochrome P-450 reductase 29 4 -OMT, (5)-3 -hydroxy-A-methylcoclaurine 4 -0-methyltransferase 30 BBE, berberine bridge enzyme 12 SalAT, salutaridinol 7-O-acetyltransferase 28 COR, codeinone reductase.25...

Fig. 8.6 Biosynthetic pathway for benzylisoquinoline alkaloid (BIA) biosynthesis in plants. TYDC tyrosine/dopa decarhoxylase, 60MT norcoclaurine b-O-methyltransfoase, 40OMT 30-hydroxy-Af-methylcoclaurine 40-O-methyltransferase, OMT ITl O-methyltransferase II-l, CYP80A1 berbamunine synthase, CYP80B1 (Si-N-methylcoclaurine 30-hydroxylase, btaber-ine bridge enzyme, SOMT scoulerine iV-methyltransferase, COR codeinone rednctase (Adopted from Ref. [3])...

Figure 4.2 Biosynthesis of benzylisoquinoline alkaloids. Enzyme abbreviations TYDC, tyrosine/dopa decarboxylase NCS, norcoclaurine synth lse 60MT, norcoclaurine 6-O-methyltransferase 4 OMT, 3 -hydroxy-/V-methylcoclaurine 4 -0-methyltransferase CYP80A, berbamunine synth lse CYP80B, N-methylcoclaurine 3 -hydroxylase BBE, berberine bridge enzyme SOMT, scoulerine 9-0-methyltransferase CYP719A, (S)-canadine synthase SAT, salutaridinol 7-O-acetyltransferase COR, codeinone reductase.

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