Acetylation serves as a protective group in noscapine biosynthesis in opium poppy

Dang, Thu-Thuy T.; Xue, Chen; Facchini, Peter J.

doi:10.1038/nchembio.1717

Cited by 72 publications

(65 citation statements)

References 22 publications

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“…Co-silencing of SalR (Supplementary Fig. 15) was unexpected based on its low nucleotide sequence identity with REPI and COR (Supplementary Table 3), although off-target transcript suppression is sometimes associated with post-transcriptional gene silencing 18 .…”

Section: Discussionmentioning

confidence: 98%

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Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy

et al. 2015

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The gateway to morphine biosynthesis in opium poppy (Papaver somniferum) is the stereochemical inversion of (S)-reticuline since the enzyme yielding the first committed intermediate salutaridine is specific for (R)-reticuline. A fusion between a cytochrome P450 (CYP) and an aldo-keto reductase (AKR) catalyzes the S-to-R epimerization of reticuline via 1,2-dehydroreticuline. The reticuline epimerase (REPI) fusion was detected in opium poppy and in Papaver bracteatum, which accumulates thebaine. In contrast, orthologs encoding independent CYP and AKR enzymes catalyzing the respective synthesis and reduction of 1,2-dehydroreticuline were isolated from Papaver rhoeas, which does not accumulate morphinan alkaloids. An ancestral relationship between these enzymes is supported by a conservation of introns in the gene fusions and independent orthologs. Suppression of REPI transcripts using virus-induced gene silencing in opium poppy reduced levels of (R)-reticuline and morphinan alkaloids and increased the overall abundance of (S)-reticuline and its O-methylated derivatives. Discovery of REPI completes the isolation of genes responsible for known steps of morphine biosynthesis.

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Section: Discussionmentioning

confidence: 98%

“…Other CYP82 members catalyze ring hydroxylations in benzylisoquinoline alkaloid biosynthesis [15][16][17][18] . Desaturation is not a common CYP function in plants, although sterol desaturases 19,20 and desaturating flavone synthases 21 have been reported.…”

Section: Discussionmentioning

confidence: 99%

Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy

et al. 2015

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“…Subsequently, all enzymes were isolated and characterized [12]. Recently the last four steps, comprising the protoberberine ring opening and formation of the phtalide ring, were found to require acetylation and deacetylation of a hydroxyl group as predicted [13].…”

Section: Biosynthetic Steps: Enzymes and Genesmentioning

confidence: 99%

Exploiting plant alkaloids

Schläger

Dräger

2016

Current Opinion in Biotechnology

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“…Elucidation of BIA metabolic pathways in plants has advanced rapidly over the past decade with a near complete catalog of biosynthetic genes and corresponding enzymes involved in the formation of major products, including berberine, sanguinarine, morphine, and noscapine (Hagel and Facchini, 2013;Dang et al, 2015). Among the BIA biosynthetic genes not yet isolated is one encoding an enzyme capable of the efficient 39-Omethylation of 1-benzylisoquinoline and/or aporphine substrates.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of O-methyltransferases Involved in the Biosynthesis of Glaucine in Glaucium flavum

2015

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Transcriptome resources for the medicinal plant Glaucium flavum were searched for orthologs showing identity with characterized O-methyltransferases (OMTs) involved in benzylisoquinoline alkaloid biosynthesis. Seven recombinant proteins were functionally tested using the signature alkaloid substrates for six OMTs: norlaudanosoline 6-OMT, 6-O-methyllaudanosoline 49-OMT, reticuline 7-OMT, norreticuline 7-OMT, scoulerine 9-OMT, and tetrahydrocolumbamine OMT. A notable alkaloid in yellow horned poppy (G. flavum [GFL]) is the aporphine alkaloid glaucine, which displays C8-C69 coupling and four O-methyl groups at C6, C7, C39, and C49 as numbered on the 1-benzylisoquinoline scaffold. Three recombinant enzymes accepted 1-benzylisoquinolines with differential substrate and regiospecificity. GFLOMT2 displayed the highest amino acid sequence identity with norlaudanosoline 6-OMT, showed a preference for the 6-O-methylation of norlaudanosoline, and O-methylated the 39 and 49 hydroxyl groups of certain alkaloids. GFLOMT1 showed the highest sequence identity with 6-O-methyllaudanosoline 49OMT and catalyzed the 6-O-methylation of norlaudanosoline, but more efficiently 49-O-methylated the GFLOMT2 reaction product 6-O-methylnorlaudanosoline and its N-methylated derivative 6-O-methyllaudanosoline. GFLOMT1 also effectively 39-O-methylated both reticuline and norreticuline. GFLOMT6 was most similar to scoulerine 9-OMT and efficiently catalyzed both 39-and 79-O-methylations of several 1-benzylisoquinolines, with a preference for N-methylated substrates. All active enzymes accepted scoulerine and tetrahydrocolumbamine. Exogenous norlaudanosoline was converted to tetra-O-methylated laudanosine using combinations of Escherichia coli producing (1) GFLOMT1, (2) either GFLOMT2 or GFLOMT6, and (3) coclaurine N-methyltransferase from Coptis japonica. Expression profiles of GFLOMT1, GFLOMT2, and GFLOMT6 in different plant organs were in agreement with the O-methylation patterns of alkaloids in G. flavum determined by high-resolution, Fourier-transform mass spectrometry.

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Acetylation serves as a protective group in noscapine biosynthesis in opium poppy

Cited by 72 publications

References 22 publications

Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy

Stereochemical inversion of (S)-reticuline by a cytochrome P450 fusion in opium poppy

Exploiting plant alkaloids

Isolation and Characterization of O-methyltransferases Involved in the Biosynthesis of Glaucine in Glaucium flavum

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