Scopolamine: a journey from the field to clinics

Ullrich, Sophie Friederike; Hagels, Hansjörg; Kayser, Oliver

doi:10.1007/s11101-016-9477-x

Cited by 52 publications

(33 citation statements)

References 135 publications

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“…The quality of Duboisia spp. plant material and the quantity of scopolamine in agricultural production depends on different abiotic factors such as climate, sunlight, soil fertilization and biotic factors [87,88]. In times of climate change, abiotic influences may become less predictable and more extreme.…”

Section: Biotechnological Approaches Of Scopolamine Production Andmentioning

confidence: 99%

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

2019

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Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, cocaine and calystegines. Although all TAs have the same basic structure, they differ immensely in their biological, chemical and pharmacological properties. Scopolamine, also known as hyoscine, has the largest legitimate market as a pharmacological agent due to its treatment of nausea, vomiting, motion sickness, as well as smooth muscle spasms while cocaine is the 2nd most frequently consumed illicit drug globally. This review provides a comprehensive overview of TAs, highlighting their structural diversity, use in pharmaceutical therapy from both historical and modern perspectives, natural biosynthesis in planta and emerging production possibilities using tissue culture and microbial biosynthesis of these compounds.

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Section: Biotechnological Approaches Of Scopolamine Production Andmentioning

confidence: 99%

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

2019

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“…Overexpressing H6H, the last rate-limiting enzyme involved in the TA biosynthetic pathway, remarkably improved the scopolamine biosynthesis and production in the TA-producing plant species of Solanaceae ( Palazón et al, 2003 ; Xia et al, 2016 ). To date, most of the engineering studies of TA biosynthesis are concerned with the PMT and H6H genes ( Ullrich et al, 2017 ). Tropinone reduction represents the branch point of TA biosynthesis; so, theoretically, genetic modification of the TR-catalyzed steps could significantly affect the TA biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Enhancing Tropane Alkaloid Production Based on the Functional Identification of Tropine-Forming Reductase in Scopolia lurida, a Tibetan Medicinal Plant

et al. 2017

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Scopolia lurida, a native herbal plant species in Tibet, is one of the most effective producers of tropane alkaloids. However, the tropane alkaloid biosynthesis in this plant species of interest has yet to be studied at the molecular, biochemical, and biotechnological level. Here, we report on the isolation and characterization of a putative short chain dehydrogenase (SDR) gene. Sequence analysis showed that SlTRI belonged to the SDR family. Phylogenetic analysis revealed that SlTRI was clustered with the tropine-forming reductases. SlTRI and the other TA-biosynthesis genes, including putrescine N-methyltransferase (SlPMT) and hyoscyamine 6β-hydroxylase (SlH6H), were preferably or exclusively expressed in the S. lurida roots. The tissue profile of SlTRI suggested that this gene might be involved in tropane alkaloid biosynthesis. By using GC-MS, SlTRI was shown to catalyze the tropinone reduction to yield tropine, the key intermediate of tropane alkaloids. With the purified recombinant SlTRI from Escherichia coli, an enzymatic assay was carried out; its result indicated that SlTRI was a tropine-forming reductase. Finally, the role of SlTRI in promoting the tropane alkaloid biosynthesis was confirmed through metabolic engineering in S. lurida. Specifically, hairy root cultures of S. lurida were established to investigate the effects of SlTRI overexpression on tropane alkaloid accumulation. In the SlTRI-overexpressing root cultures, the hyoscyamine contents were 1.7- to 2.9-fold higher than those in control while their corresponding scopolamine contents were likewise elevated. In summary, this functional identification of SlTRI has provided for a better understanding of tropane alkaloid biosynthesis. It also provides a candidate gene for enhancing tropane alkaloid biosynthesis in S. lurida via metabolic engineering.

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“…Nocquet et al attempted a total synthesis approach to produce the compound scopolamine (3), however their low yield of 16% does not make this method economically feasible [2]. A major problem for the commercial production of scopolamine (3) in hairy root cultures is achieving industrial level yields [132]. Researchers are now focused on metabolic engineering plants that produce these important compounds to increase final yields, or engineering microorganisms that will be able to produce the compounds from simple sugars or common precursors.…”

Section: Metabolic Engineeringmentioning

confidence: 99%

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

et al. 2016

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Abstract:The tropane and granatane alkaloids belong to the larger pyrroline and piperidine classes of plant alkaloids, respectively. Their core structures share common moieties and their scattered distribution among angiosperms suggest that their biosynthesis may share common ancestry in some orders, while they may be independently derived in others. Tropane and granatane alkaloid diversity arises from the myriad modifications occurring to their core ring structures. Throughout much of human history, humans have cultivated tropane-and granatane-producing plants for their medicinal properties. This manuscript will discuss the diversity of their biological and ecological roles as well as what is known about the structural genes and enzymes responsible for their biosynthesis. In addition, modern approaches to producing some pharmaceutically important tropanes via metabolic engineering endeavors are discussed.

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Scopolamine: a journey from the field to clinics

Cited by 52 publications

References 135 publications

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Enhancing Tropane Alkaloid Production Based on the Functional Identification of Tropine-Forming Reductase in Scopolia lurida, a Tibetan Medicinal Plant

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

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