- Compositions and methods for producing benzylisoquinoline alkaloids
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The present invention relates to host cells that produce compounds that are characterized as benzylisoquinolines, as well as select precursors and intermediates thereof. The host cells comprise one, two or more heterologous coding sequences wherein each of the heterologous coding sequences encodes an enzyme involved in the metabolic pathway of a benzylisoquinoline, or its precursors or intermediates from a starting compound. The invention also relates to methods of producing the benzylisoquinoline, as well as select precursors and intermediates thereof by culturing the host cells under culture conditions that promote expression of the enzymes that produce the benzylisoquinoline or precursors or intermediates thereof.
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Page/Page column 3-4; 14
(2016/05/19)
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- Rat CYP2D2, not 2D1, is functionally conserved with human CYP2D6 in endogenous morphine formation
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The assumption that CYP2D1 is the corresponding rat cytochrome to human CYP2D6 has been revisited using recombinant proteins in direct enzyme assays. CYP2D1 and 2D2 were incubated with known CYP2D6 substrates, the three morphine precursors thebaine, codeine and (R)-reticuline. Mass spectrometric analysis showed that rat CYP2D2, not 2D1, catalyzed the 3-O-demethylation reaction of thebaine and codeine. In addition, CYP2D2 incubated with (R)-reticuline generated four products corytuberine, pallidine, salutaridine and isoboldine while rat CYP2D1 was completely inactive. This intramolecular phenol-coupling reaction follows the same mechanism as observed for CYP2D6. Michaelis-Menten kinetic parameters revealed high catalytic efficiencies for rat CYP2D2. These findings suggest a critical evaluation of other commonly accepted, however untested, CYP2D1 substrates.
- Grobe, Nadja,Kutchan, Toni M.,Zenk, Meinhart H.
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experimental part
p. 1749 - 1753
(2012/08/29)
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- PURIFICATION AND CHARACTERIZATION OF A CYTOCHROME P450 ENZYME FROM PIG LIVER, CATALYZING THE PHENOL OXIDATIVE COUPLING OF (R)-RETICULINE TO SALUTARIDINE, THE CRITICAL STEP IN MORPHINE BIOSYNTHESIS
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The cytochrome P450 enzyme catalyzing the conversion of (R)-reticuline to salutaridine in the presence of cytochrome c reductase, NADPH and O2 was purified to homogeneity from pig liver and shown to be a highly regio- and stereoselective enzyme.This finding supports the view that the occurrence of morphine in mammals is of endogenous and not of dietary origin.
- Amann, Tobias,Roos, Peter H.,Huh, Hoon,Zenk, Meinhart H.
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p. 425 - 440
(2007/10/02)
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- Formation of the morphine precursor salutaridine is catalyzed by a cytochrome P-450 enzyme in mammalian liver
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A highly regio- and stereoselective microsomal-bound cytochrome P-450 NADPH dependent enzyme has been discovered in pig liver which is responsible for the intramolecular phenol oxidative coupling of (R)-reticuline to salutaridine, thus giving rise to the morphine skeleton in mammals.
- Amann,Zenk
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p. 3675 - 3678
(2007/10/02)
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- Alkaloids of Ocotea brachybotra
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Aporphine, proaporphine and morphinane alkaloids were isolated from the leaves of a Brazilian Lauracea, Ocotea brachybotra (Meiss.) Mez. The known alkaloids were identified through their physico-chemical properties as: (I) (±)-glaziovine, (II) dicentrine, (III) ocopodine, (IV) cassythicine, (V) predicentrine, (VI) leucoxine, (IX) sinacutine and (X) pallidine. The structure of (VI) leucoxine was confirmed by a detailed analysis of the N.M.R. spectra recorded in various conditions. New morphinane alkaloids, (XI) ocobotrine and (XII) 14-episinomenine, having the unusual B/C-trans configuration were also isolated. Their structures were determined using spectroscopic methods and chemical correlations.
- Vecchietti,Casagrande,Ferrari
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p. 767 - 779
(2007/10/04)
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