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Opium poppy: blueprint for an alkaloid factory

Profile image of Benjamin P MacLeodBenjamin P MacLeod

2007, Phytochemistry Reviews

https://doi.org/10.1007/S11101-006-9042-0
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28 pages

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Abstract
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The opium poppy, known for its rich content of benzylisoquinoline alkaloids like morphine and codeine, serves as a key model for exploring alkaloid metabolism in plants. This review outlines a comprehensive strategy integrating biochemical, genomic, and metabolomic methods to create a biological blueprint for optimizing alkaloid production. It emphasizes the collaboration of phloem cell types and dedifferentiated cultures in synthesizing alkaloids, while acknowledging advancements in genomics that have led to the identification of novel biosynthetic genes, ultimately enhancing the potential for transforming this valuable medicinal plant.

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    Kg Ramawat

    Herbal Drugs: Ethnomedicine to Modern Medicine, 2009

    Considerable progress has been made in our healthcare system, in particular with respect to sensitive diagnostic tools, reagents and very effective and precise drugs. On the other hand, high-throughput screening technology can screen vast numbers of compounds against an array of targets in a very short time, and leads thus obtained can be further explored. In developing countries, the exploding population exerts pressure not only on natural resources but also on the human population itself, whose members strive to become successful and advance in society. This leads to increased blood pressure, anxiety, obesity-associated lipid disorders, cardiovascular diseases and diabetes. Most of these diseases result in disturbed family life, including sexual behaviour. Despite technological developments, herbal drugs still occupy a preferential place in a majority of the population in the Third World and terminal patients in the West. Herbal drugs, in addition to being cost effective and easily accessible, have been used since time immemorial and have passed the test of time without having any side effects. The multitarget effects of herbs (holistic approaches) are the fundamental basis of their utilization. This approach is already used in traditional systems of medicine like Ayurveda, which has become more popular in the West in recent years. However, the integration of modern science with traditional uses of herbal drugs is of the utmost importance if ones wishes to use ancient knowledge for the betterment of humanity. This book will try to bridge this gap and will be a valuable source for herbalists, traditional and modern medical practitioners, and researchers in botany, ethnobotany, pharmacy, phytochemistry and agriculture. Contributions on herbs used for beneficial effects on memory, sexual behaviour, neurodegeneration, erectile dysfunction, inflammation, cardiovascular diseases, cancer prevention, stroke and central nervous system disorders will provide vital information to readers. Finally, I would like to acknowledge my contributors, who have gone to great lengths to ensure the high scientific quality of the book. I would also like to thank my colleagues at Springer.

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    Ali Ufki'nin Mecmua-i Saz ü Söz'ündeki İlaç Reçeteleri - Pharmaceutical Prescriptions in The Mecmua-i Saz u Söz of Ali Ufki
    Burcu Şen

    Osmanlı Bilimi Araştırmaları, 2018

    Ali Ufki (aka Wojciech Bobowski and Albertus Bobovius, 1610?-1675?) was a Polish nobleman who has been taken captive during the Polish-Ottoman war of 1633-34. He lived for about twenty years in the Topkapı Palace where he served as a musician, a music teacher and a dragoman. He compiled an anthology of the Ottoman music entitled Mecmua-i Saz ü Söz (Collection of Instrumental and Vocal Works) which contains pieces he both notated and composed. This article aims to examine the pharmaceutical prescriptions written on the marginalia of the London copy of Mecmua-i Saz ü Söz (MS BL-Sloane 3114), and to explore the use and effects of the plants and pharmaceutical drugs employed in these prescriptions. This study determined that the effects of most of them were supported by present-day scientific studies, and the uses of some prescriptions matched with current ethnobotanical uses. Formulated for both internal and external use, these remedies were prescribed for conditions such as pediculosis, headache, pertussis, lumbago, halitosis, diarrhea, and wounds. Pastes, decoctions, and ointments were among the pharmaceutical forms employed.

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    Crystal structure of norcoclaurine-6-O-methyltransferase a key rate-limiting step in the synthesis of benzylisoquinoline alkaloids
    Renaud Dumas

    The Plant Journal, 2016

    Growing pharmaceutical interest in benzylisoquinoline alkaloids (BIA) coupled with their chemical complexity make metabolic engineering of microbes to create alternative platforms of production an increasingly attractive proposition. However, precise knowledge of rate-limiting enzymes and negative feedback inhibition by end-products of BIA metabolism is of paramount importance for this emerging field of synthetic biology. In this work we report the structural characterization of (S)-norcoclaurine-6-O-methyltransferase (6OMT), a key rate-limiting step enzyme involved in the synthesis of reticuline, the final intermediate to be shared between the different end-products of BIA metabolism, such as morphine, papaverine, berberine and sanguinarine. Four different crystal structures of the enzyme from Thalictrum flavum (Tf 6OMT) were solved: the apoenzyme, the complex with S-adenosyl-L-homocysteine (SAH), the complexe with SAH and the substrate and the complex with SAH and a feedback inhibitor, sanguinarine. The Tf 6OMT structural study provides a molecular understanding of its substrate specificity, active site structure and reaction mechanism. This study also clarifies the inhibition of Tf 6OMT by previously suggested feedback inhibitors. It reveals its high and time-dependent sensitivity toward sanguinarine.

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    Manipulating the Biosynthesis of Bioactive Compound Alkaloids for Next-Generation Metabolic Engineering in Opium Poppy Using CRISPR-Cas 9 Genome Editing Technology
    Yağız Alagöz

    Scientific reports, 2016

    Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated9 (Cas9) endonuclease system is a powerful RNA-guided genome editing tool. CRISPR/Cas9 has been well studied in model plant species for targeted genome editing. However, few studies have been reported on plant species without whole genome sequence information. Currently, no study has been performed to manipulate metabolic pathways using CRISPR/Cas9. In this study, the type II CRISPR/SpCas9 system was used to knock out, via nonhomologous end-joining genome repair, the 4'OMT2 in opium poppy (Papaver somniferum L.), a gene which regulates the biosythesis of benzylisoquinoline alkaloids (BIAs). For sgRNA transcription, viral-based TRV and synthetic binary plasmids were designed and delivered into plant cells with a Cas9 encoding-synthetic vector by Agrobacterium-mediated transformation. InDels formed by CRISPR/Cas9 were detected by sequence analysis. Our results showed that the biosynthesis of BIAs (...

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