Benzylisoquinoline alkaloids berberine bridge enzyme

PARK, S.-U., JOHNSON, A.G., PENZES-YOST, C FACCHINI, P.J., Analysis of promoters from tyrosine/dihydroxyphenylalanine decarboxylase and berberine bridge enzyme genes involved in benzylisoquinoline alkaloid biosynthesis in opium poppy. Plant Mol. Biol., 1999,40,121-131. 

BIRD, D.A., FACCHINI, P.J., Berberine bridge enzyme, a key branch-point enzyme in benzylisoquinoline alkaloid biosynthesis, contains a vacuolar-sorting determinant. Planta, 2001,213, 888-897. 

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,...

Morphine and codeine are members of the large and diverse group of benzylisoquinoline alkaloids, of which morphine and sanguinarine share a common biosynthetic pathway, beginning with the condensation of two L-Tyr derivatives to produce the central precursor (S)-norcoclaurine yields (S)-reticuline, the last common intermediate in the biosynthesis of both sanguinarine and morphine. Berberine bridge enzyme (BBE) catalyzes the conversion of (S)-reticuline to (S)-scoulerine, the first committed step in the sanguinarine pathway. Alternatively, (S)-reticuline can be isomerized to its (R)-epimer as the first step in the formation of morphine. Since the pathway from tyrosine to (S)-reticuline is also known at the enzyme level, the conversion of L-tyrosine to macarpine involves a total of 19 enzymes which are now at least partially characterized. 

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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