Plant Secondary Chemistry: from Biochemistry to Applications
Facchini, Peter .
Milk of the Poppy: Alkaloid Biosynthesis in Plants and Beyond.
In 1806, a pharmacist’s apprentice named Friedrich Sertürner isolated an alkaline component from opium he called morphium, after Morpheus the Greek god of dreams. Morphine, as it became known, was not only the first isolated alkaloid, but also the first active principle isolated from any medicinal plant. The isolation of other opium alkaloids soon followed including noscapine, which is now used as a cough suppressant and is being intensively investigated as an anticancer drug, in 1817 by the chemist Pierre Robiquet. By 1818, the physician François Magendie first described the use of morphine as a pain reliever and the drug soon became widely available in Western Europe. Opium poppy remains the sole commercial source for morphine, the gold standard in pain management, and other narcotic analgesics including codeine and semi-synthetic opiate derivatives such as oxycodone. The molecular structure of morphine was eventually deduced in 1925 by the chemist Sir Robert Robinson, and the first total synthesis was reported in 1952 by Marshall D. Gates Jr., confirming the empirical formula. Elegant radiotracer experiments conducted by Sir Alan Battersby and others in the 1960s led to a remarkably accurate biosynthetic scheme for morphine, although a proposed pathway for noscapine biosynthesis remained obscure. Now, two centuries after the initial isolation of morphine and noscapine, all relevant genes involved in the complex biosynthesis of these and other major alkaloids in opium poppy have been identified. Other benzylisoquinoline alkaloids produced by the plant display diverse molecular scaffolds and an array of pharmacological properties, and include the vasodilator papaverine, the antimicrobial agent sanguinarine, and the anxiolytic compound magnoflorine. The recent application of integrated functional genomics methodologies in opium poppy has facilitated the discovery of all relevant biosynthetic genes responsible for the formation of these alkaloids, in addition to morphine and noscapine. To date, more than 30 alkaloid biosynthetic genes belonging to over a dozen different enzyme families have been isolated from opium poppy and functionally characterized. Most alkaloid biosynthetic enzymes in opium poppy have been localized to sieve elements of the phloem. However, the final conversions of some pathways, including those involved in the formation of morphine and noscapine, occur in laticifers, which contain the alkaloid-rich latex exuded upon lancing of unripe seed capsules. The availability of an extensive genomics toolbox has created unprecedented opportunities to investigate new aspects of alkaloid metabolism in opium poppy with both basic and applied implications.
1 - University of Calgary, Department of Biological Sciences, 2500 University Drive N.W., Calgary, AB, T2N 1N4, Canada
plant secondary chemistry
Presentation Type: Symposium Presentation
Candidate for Awards:None