Protoberberine alkaloids, berberine bridge enzyme

Fig. 10.2 Reaction catalyzed by the berberine bridge enzyme (BBE) along the biosynthetic pathway leading to protoberberine, berberine and benzo[c]phenanthridine alkaloids.

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... 

Berberine bridge enzyme catalyses are specialized step in protoberberine alkaloid biosynthesis similar genes and proteins are, however, widely present in higher plants, indicating common ancestry (Fig. 7.17c). BBE or similar proteins, which share a number of common conserved sites (Table 7.8), could also be found in fungi and bacteria. A similar pattern can be seen in the distribution of CR (Fig. 7.17d, Table 7.9). 

Berberine or protoberberine alkaloids [such as stylopine (79)] may be converted into alkaloids of the protopine type (60) (Fig. 32.24) (Geissman and Crout, 1969 Hartmann, 1991). Highly specific microsomal cytochrome P-450-de-pendent enzymes from cells of Eschscholtzia californica (and other species of the Papaveraceae and Fumariaceae) introduce two methylenedioxy bridges into (5)-scoulerine (72) to form (5)-stylopine (79), which is, in turn, an important precursor of the protopine, phthalideisoquinoline, and benzophenanthridine groups (Hartmann, 1991). 

Steffens P, Nagakura N, Zenk MH (1984) The berberine bridge forming enzyme in tetrahydro-protoberberine biosynthesis. Tetrahedron Lett 25 951-952 Sumimoto Chemicals Co Ltd (1982) Berberine alkaloid production by tissue culture. Jpn Kokai Tokkyo Koho 57,144,992 (Cl C 12pl7/18)... 

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