ArticleThe Journal of biological chemistry2009
Mammalian cytochrome P450 enzymes catalyze the phenol-coupling step in endogenous morphine biosynthesis.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 61 citations in OpenAlex.
- Cytochrome P450The Journal of biological chemistry · 2025Article
- Mapping and Exploiting the Promiscuity of OxyB toward the Biocatalytic Production of Vancomycin Aglycone Variants.ACS catalysis · 2020Article
- Substrate-Assisted Hydroxylation andACS catalysis · 2020Article
- Human Enzymes for Organic Synthesis.Angewandte Chemie (International ed. in English) · 2018Review
- Formation and Cleavage of C-C Bonds by Enzymatic Oxidation-Reduction Reactions.Chemical reviews · 2018Review
- Cross-linking of dicyclotyrosine by the cytochrome P450 enzyme CYP121 fromThe Journal of biological chemistry · 2017Article
- A combinatorial approach for the discovery of cytochrome P450 2D6 inhibitors from nature.Scientific reports · 2017Article
- Divergent non-heme iron enzymes in the nogalamycin biosynthetic pathway.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Bifunctional CYP81AA proteins catalyse identical hydroxylations but alternative regioselective phenol couplings in plant xanthone biosynthesis.Nature communications · 2016Article
- Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli.Nature communications · 2016Article
- Transition metal-free intramolecular regioselective couplings of aliphatic and aromatic C-H bonds.Scientific reports · 2016Article
- CYP96T1 of Narcissus sp. aff. pseudonarcissus Catalyzes Formation of the Para-Para' C-C Phenol Couple in the Amaryllidaceae Alkaloids.Frontiers in plant science · 2016Article
- Cytochrome P450 3A Enzymes Catalyze the O6-Demethylation of Thebaine, a Key Step in Endogenous Mammalian Morphine Biosynthesis.The Journal of biological chemistry · 2015Article
- Nitrogen-Containing Constituents of Black Cohosh: Chemistry, Structure Elucidation, and Biological Activities.Recent advances in phytochemistry · 2015Article
- Article
- Functional diversity of 2-oxoglutarate/Fe(II)-dependent dioxygenases in plant metabolism.Frontiers in plant science · 2014Review
- Unusual cytochrome p450 enzymes and reactions.The Journal of biological chemistry · 2013Review
- Towards a molecular understanding of the biosynthesis of amaryllidaceae alkaloids in support of their expanding medical use.International journal of molecular sciences · 2013Review
- Rat CYP2D2, not 2D1, is functionally conserved with human CYP2D6 in endogenous morphine formation.FEBS letters · 2012Article
- An (R)-specific N-methyltransferase involved in human morphine biosynthesis.Archives of biochemistry and biophysics · 2011Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
A cytochrome P450 (P450) enzyme in porcine liver that catalyzed the phenol-coupling reaction of the substrate (R)-reticuline to salutaridine was previously purified to homogeneity (Amann, T., Roos, P. H., Huh, H., and Zenk, M. H. (1995) Heterocycles 40, 425-440). This reaction was found to be catalyzed by human P450s 2D6 and 3A4 in the presence of (R)-reticuline and NADPH to yield not a single product, but rather (-)-isoboldine, (-)-corytuberine, (+)-pallidine, and salutaridine, the para-ortho coupled established precursor of morphine in the poppy plant and most likely also in mammals. (S)-Reticuline, a substrate of both P450 enzymes, yielded the phenol-coupled alkaloids (+)-isoboldine, (+)-corytuberine, (-)-pallidine, and sinoacutine; none of these serve as a morphine precursor. Catalytic efficiencies were similar for P450 2D6 and P450 3A4 in the presence of cytochrome b(5) with (R)-reticuline as substrate. The mechanism of phenol coupling is not yet established; however, we favor a single cycle of iron oxidation to yield salutaridine and the three other alkaloids from (R)-reticuline. The total yield of salutaridine formed can supply the 10 nm concentration of morphine found in human neuroblastoma cell cultures and in brain tissues of mice.
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