Benzophenanthridine alkaloid biosynthesis

KUTCHAN, T.M., DITTRICH, H., Characterization and mechanism of the berberine bridge enzyme, a covalently flavinylated oxidase of benzophenanthridine alkaloid biosynthesis in plants, J. Biol. Chem., 1995,270,24475-24481. 

MAHADY, G.B., BEECHER, C.W., Elicitor-stimulated benzophenanthridine alkaloid biosynthesis in bloodroot suspension cultures is mediated by calcium. Phytochemistry, 1994,37,415-419. 

PARK, S.-U., YU, M., FACCHINI, P.J., Antisense RNA-mediated suppression of benzophenanthridine alkaloid biosynthesis in transgenic cell cultures of California poppy. Plant Physiol., 2002,128, 696-706. 

TANAHASHI, T., ZENK, M.H., Elicitor induction and characterization of microsomal protopine-6-hydroxylase, the central enzyme in benzophenanthridine alkaloid biosynthesis. Phytochemistry, 1990,29,1113-1122. 

Kutchan, T.M. and Zenk, M.H. (1993) Enzymology and molecular biology of benzophenanthridine alkaloid biosynthesis. /. Tlant Res. (Special Issue), 3, 165-73. 

S)-Reticuline is a branch-point intermediate in the biosynthesis of most BAs. Most work has focused on branch pathways leading to the benzophenanthridine (e.g., sanguinarine), protoberberine (e.g., berberine), and morphinan (e.g., morphine and codeine) alkaloids.19 Most enzymes involved have been isolated, many have been purified, and four corresponding cDNAs have been cloned.19 The first committed step in benzophenanthridine and protoberberine alkaloid biosynthesis involves the conversion of (S)-reticuline to (5)-scoulerine by the berberine bridge enzyme (BBE) (Fig.7.2). BBE was purified from Berberis beaniana,20 corresponding cDNAs were cloned from E. californica and B. stolonifera,21 22 and BBE genes have been isolated from P. somniferum and E. californica.23,24... 

Figure 2.7 Biosynthesis of protopine and the benzophenanthridine alkaloids. STS, stylopine synthase SNMT, stylopine N-methyltransferase DBOX, dihydrosanguinarine oxidase SanR, sanguinarine reductase.

Pharmacological Activity Other Biological Activity Protoberberidine Alkaloids Biosynthesis Biological Activity Protopine Alkaloids Benzophenanthridine Alkaloids Phthalideisoquinoline Alkaloids Rhoeadane Alkaloids Dibenzopyrrocoline Alkaloids Pavine and Isopavine (Argemone) Alkaloids Cularine Alkaloids Bisbenzylisoquinoline Alkaloids Biological Activity... 

Fig. 3 Primary precnrsor-end product relationships in alkaloid biosynthesis. Color codes blue, terpene indole alkaloids green, benzophenanthridine alkaloids gray, benzylisoquinoline alkaloids red, quinolizi-dine alkaloids yellow, pyridine alkaloids pink, tropane alkaloids...

Amann M, Nagakura N, Zenk MH (1984) (S>Tetrahydroprotoberberineoxidase, the final enzyme in protoberberine biosynthesis. Tetrahedron Lett 25 953-954 Berlin J, Forche E, Wray V, Hammer J, Hosel W (1983) Formation of benzophenanthridine alkaloids by suspension cultures of Eschscholtzia califomica, Z Naturforsch 38C 346-r352 Bohm H, Franke J (1982) Accumulation and excretion of alkaloids by Macleaya microcarpa cell cultures, I. Experiments on solid medium. Biochem Physiol Pflanz 177 345--356 Bohm H, Franke J, Lammel L (1980) Chelidonium mafus alkaloids. GDR Pat 143, 270 (Cl C12P17/00)... 

Alkaloids, such as benzophenanthridines, are potentially useful as pharmaceuticals. Because of this, there has been much interest in understanding the biosynthesis of these compounds. A common metabolite,... 

M. Rueffer and M.H. Zenk, S-Adenosyl-L-methionine (S)-7,8,13,14-Tetra-hydroberberine-cis-N-methyltransferase, a branch point enzyme in the biosynthesis of benzophenanthridine and protopine alkaloids. Tetrahedron Lett. 

The benzophenanthridine skeleton is encountered in approximately 30 alkaloids, principally of the family Papaveraceae (Cordell, 1978a). In contrast to the biosynthesis of protopine alkaloids, phenanthridine alkaloids are synthesized in the cytoplasm (Hartmann, 1991). This type of system arises from a protoberberine precursor by fission of the C-6-N bond and recyclization. The biogenetic sequence leading to chelidonine (80) biosynthesis in Chelidonium majus has been supported by feeding experiments with multiply-labeled (-t-)-reticuline [(5)-reticuline] (20) and with labeled stylopine (79) (Fig. 32.25) (Hutchinson, 1986 Sim ek, 1985 Tanahashi and Zenk, 1988). (5)-Z-V-Methylstylopine and protopine (60) have been shown to be metabolites in this pathway. Reticuline is oxidatively cyclized to ( —)-scoulerine (72). Formation of two methylenedioxy groups results in the formation of stylopine (79) (Hartmann, 1991). 

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