Chemistry and biology of calystegines

Dräger, Birgit

doi:10.1039/b300289f

Cited by 125 publications

(58 citation statements)

References 133 publications

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“…Tropinone represents a key branch point in the pathway (Hashimoto et al, 1992;Nakajima et al, 1993). Tropinone reductase II reduces tropinone to pseudotropine, which directly leads to the synthesis of calystegines, a class of polyhydroxylated alkaloids that resemble monosaccharides in structure and act as glycosidase inhibitors (Dräger, 2004). In contrast, tropinone reductase I reduces tropinone to tropine, which leads to the biosynthesis of hyoscyamine and scopolamine.…”

Section: Introductionmentioning

confidence: 99%

A Root-Expressed l-Phenylalanine:4-Hydroxyphenylpyruvate Aminotransferase Is Required for Tropane Alkaloid Biosynthesis in Atropa belladonna

et al. 2014

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The tropane alkaloids, hyoscyamine and scopolamine, are medicinal compounds that are the active components of several therapeutics. Hyoscyamine and scopolamine are synthesized in the roots of specific genera of the Solanaceae in a multistep pathway that is only partially elucidated. To facilitate greater understanding of tropane alkaloid biosynthesis, a de novo transcriptome assembly was developed for Deadly Nightshade (Atropa belladonna). Littorine is a key intermediate in hyoscyamine and scopolamine biosynthesis that is produced by the condensation of tropine and phenyllactic acid. Phenyllactic acid is derived from phenylalanine via its transamination to phenylpyruvate, and mining of the transcriptome identified a phylogenetically distinct aromatic amino acid aminotransferase (ArAT), designated Ab-ArAT4, that is coexpressed with known tropane alkaloid biosynthesis genes in the roots of A. belladonna. Silencing of Ab-ArAT4 disrupted synthesis of hyoscyamine and scopolamine through reduction of phenyllactic acid levels. Recombinant Ab-ArAT4 preferentially catalyzes the first step in phenyllactic acid synthesis, the transamination of phenylalanine to phenylpyruvate. However, rather than utilizing the typical keto-acid cosubstrates, 2-oxoglutarate, pyruvate, and oxaloacetate, Ab-ArAT4 possesses strong substrate preference and highest activity with the aromatic keto-acid, 4-hydroxyphenylpyruvate. Thus, Ab-ArAT4 operates at the interface between primary and specialized metabolism, contributing to both tropane alkaloid biosynthesis and the direct conversion of phenylalanine to tyrosine.

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Section: Introductionmentioning

confidence: 99%

A Root-Expressed l-Phenylalanine:4-Hydroxyphenylpyruvate Aminotransferase Is Required for Tropane Alkaloid Biosynthesis in Atropa belladonna

et al. 2014

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“…The physico-chemical data of TAs with a tropane skeleton were reviewed by Boit (1961), and of calystegines by Dräger (2004). The chemical and physical characteristics of atropine, (-)-hyoscyamine and (-)-scopolamine, have been summarised in an EFSA opinion on animal feed (EFSA, 2008).…”

Section: Chemistry Of Tropane Alkaloidsmentioning

confidence: 99%

“…down to -1.6 for the pentahydroxy alkaloids). Due to their hydrophilic properties they remain in the aqueous phase during common alkaloid extraction procedures (Dräger, 2004).…”

Section: Chemistry Of Tropane Alkaloidsmentioning

confidence: 99%

Scientific Opinion on Tropane alkaloids in food and feed

2013

EFS2

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The European Food Safety Authority (EFSA) was asked to deliver a scientific opinion on the risks to human and animal health related to the presence of tropane alkaloids (TAs) in food and feed. TAs are secondary metabolites which occur in several plant families. Although more than 200 different TAs have been identified in various plants, respective data on toxicity and occurrence in food and feed are limited. Therefore, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) could only perform a risk assessment on (-)-hyoscyamine and (-)-scopolamine, the two TAs for which occurrence and toxicity data were available. Since the pharmacological effects of (-)-hyoscyamine and (-)-scopolamine occur within a short time after administration, the CONTAM Panel concluded that it was appropriate to establish an Acute Reference Dose (ARfD) for these substances. Based on the results for decreased heart rate in a human volunteer study, the CONTAM Panel established a group ARfD of 0.016 µg/kg body weight (b.w.) expressed as the sum of (-)-hyoscyamine and (-)-scopolamine, assuming equivalent potency. Results on TAs in 124 food and 611 feed samples were collected in two Member States. Most of the food and feed samples were left-censored (below limit of detection/limit of quantification). A reliable exposure estimate was only possible for one food and one age class (toddlers). Based on the limited information, the CONTAM Panel concluded that the dietary exposure of toddlers could be up to seven times the group ARfD and could exceed the group ARfD on approximately 11 to 18 % of consumption days. TA toxicosis in livestock and companion animals is relatively rare. © European SUMMARYFollowing a request from the European Commission, the EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on the risks to human and animal health related to the presence of tropane alkaloids (TA) in food and feed.TAs are secondary metabolites which naturally occur in plants of several families including Brassicaceae, Solanaceae (e.g. mandrake, henbane, deadly nightshade, Jimson weed) and Erythroxylaceae (including coca). The TAs are found in all parts of the plants and are responsible for the toxic effects of some of these plants. TAs contain an azabicyclo[3.2.1]octane ring structure. The common structural element is the tropane skeleton, (1R,5S)-8-methyl-8-azabicyclo[3.2.1]octane. The group of TAs comprises more than 200 compounds and the wide range of compounds occurring especially in the Solanaceae family arises from the esterification of tropine with a variety of acids, such as acetic acid, propanoic acid, isobutyric acid, isovaleric acid, 2-methylbutyric acid, tiglic acid, (+)-α-hydroxy-β-phenylpropionic acid, tropic acid, and atropic acid.Although more than 200 different TAs were so far identified in various plants, respective data on their occurrence in food and feed and on toxicity are limited. The most studied TAs are (-)-hyoscyamine and (-)-scopolamine, which in contrast to the (+...

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“…Conversely, the 3β-hydroxyl-substituted tropane alkaloids constitute a rather small group of compounds, including 3β-acetoxytropane and 3β-tigloyloxytropane. It bears stressing that the biosynthetic pathway that leads to the formation of these compounds also leads to the formation of CAs, which are nonesterified polyhydroxylated nortropane alkaloids whose structure consists solely of the tropane ring and a varying number of hydroxyl substituents (three, four, or five) (Dräger 2004).…”

Section: Introductionmentioning

confidence: 99%

“…(Convolvulaceae) (Tepfer et al 1988). Research interest in the CAs is on the rise, particularly in view of their potential antiviral, anticancer, and antidiabetic effects (Dräger 2004).…”

Section: Introductionmentioning

confidence: 99%

Tropane alkaloids and calystegines as chemotaxonomic markers in the Solanaceae

Pigatto

Blanco

Mentz

et al. 2015

An. Acad. Bras. Ciênc.

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This study assessed the occurrence and distribution of tropane alkaloids and calystegines in genera of the family Solanaceae to identify patterns of distribution and make evolutionary inferences. A database of tropane alkaloids and calystegines occurrences was constructed from the results of a search of scientific websites and a hand search of periodicals. The terms "Solanaceae", "tropane alkaloids", and "calystegines" were used as index terms for a full-text article search unrestricted by date of publications. The number of occurrence and chemical diversity indices were calculated and cluster analysis and principal components analysis were performed. Overall, 996 occurrences were reported, 879 of tropane alkaloids (88.3%) and 117 of calystegines (11.7%). The calystegines were significantly more relevant than tropane alkaloids for characterization of distinct groups of genera on both analyses performed here. This corroborates the trend toward a chemical dichotomy observed on database analysis and somewhat reinforces the correlation between geographic distribution and occurrence of secondary metabolites, as the presence of calystegines alone (without tropane alkaloids) was only reported in genera that have South America as their center of diversity.

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Chemistry and biology of calystegines

Cited by 125 publications

References 133 publications

A Root-Expressed l-Phenylalanine:4-Hydroxyphenylpyruvate Aminotransferase Is Required for Tropane Alkaloid Biosynthesis in Atropa belladonna

A Root-Expressed l-Phenylalanine:4-Hydroxyphenylpyruvate Aminotransferase Is Required for Tropane Alkaloid Biosynthesis in Atropa belladonna

Scientific Opinion on Tropane alkaloids in food and feed

Tropane alkaloids and calystegines as chemotaxonomic markers in the Solanaceae

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