Berberine biosynthetic precursor

The biosynthetic precursor of berberine is (S)-reticuline, the biosynthesis of which was reviewed in Section 1.4. First, (S)-reticuline is converted into (S)-scoulerine, and the berberine bridge enzyme responsible for this step has been purified from the cultivated cells of Berberis beaniana (Berberidaceae) [7]. Through enzymatic reaction, Imol of oxygen is digested, and when the Ai-methyl moiety of (S)-reticuline is labeled with ( in the Figure), H2O labeled with is obtained. 

Another essential factor that might induce the production of benzylisoquinolines could be the addition of biosynthetic precursors to the medium. Kamimura et al. (1976), for instance, described a stimulation of thebaine formation with the addition of tyrosine and dopa to the medium of Papaver bracteatum cultures. An increase from 0.05% of dry weight to 0.07% in the production of berberine in Argemone me-xicana (Menispermaceae) suspension cultures (Khanna et al. 1982) also was due to the addition of tyrosine, whereas phenylalanine in the medium only stimulated the growth index and the berberine yield remained constant. 

Narcotine.—Previous results had allowed the biosynthetic route to narcotine (83) to be traced as far as (-)-(5)-scoulerine (68). Further results show that isocorypalmine (82) and canadine (80) are effective precursors for (83) in Papaver somniferum. The biosynthesis of narcotine may thus be further defined as (68) -> (82) - (80) - (83). [It appears that aromatization of canadine (80) to give berberine (84) involves stereospecific removal of hydrogen from C-8 of (80).] As in... 

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. 

Barton DHR, Cohen T (1957) In Festschrift Dr A Stoll, Birkhauser, Basel, p 117 Barton DHR, Kirby GW, Taylor JB, Thomas GM (1963) Phenol oxidation and biosynthesis, part VI. The biogenesis of amaryllidaceae alkaloids. J Chem Soc 4545—4558 Barton DHR, Hesse RH, Kirby GW (1965) Phenol oxidation and biosynthesis, part VIII. Investigations on the biosynthesis of berberine and protopine. J Chem Soc 6379-6389 Barton DHR, Bracho RD, Potter CJ, Widdowson DA (1974) Phenol oxidation and biosynthesis, part XXIV. Origin of chirality in the erythrinan system and derivation of the lactone rings of a- and ]3-erythroidine. J Chem Soc Perkin Trans 1 2278-2283 Basmadjian GP, Paul AG (1971) The isolation of an O-methyltransferase from peyote and its role in the biosynthesis of mescaline. Uoydia 34 91-93 Basmadjian GP, Hussain SF, Paul AG (1978) Biosynthetic relationships between phenethylamine and tetrahydroisoquinoline alkaloids in peyote. Lloydia 41 375-380 Battersby AR, Binks R, Francis RJ, McCaldin DJ, Ramuz H (1964) Alkaloid biosynthesis, part IV. 1-Benzylisoquinolines as precursors of thebaine, codeine and morphine. J Chem Soc 3600-3610... 

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