Isolation, expression and biochemical characterization of recombinant hyoscyamine-6β-hydroxylase from <i>Brugmansia sanguinea</i> – tuning the scopolamine production

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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“…In 2018, Fischer et. al., published results of SUMO-tagged H6H from Brugmansia sanguinea to have a K m value of ~60μM [ 112 ].…”

Section: Biotechnological Approaches Of Scopolamine Production Andmentioning

confidence: 99%

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

2019

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“…In vitro assays showed that atropine is enzymatically converted into scopolamine via the intermediate anisodamine [27]. This chemical transformation is conceptualized as two concerted reactions: (i) the hydroxylation of atropine followed by (ii) the cyclization of anisodamine to form an epoxide between the carbon atoms C6 and C7.…”

Section: Discussionmentioning

confidence: 99%

“…H6H has been cloned from different Solanaceae [29]. When the heterologously expressed enzyme was incubated with atropine, it produced anisodamine and scopolamine but in a ratio of 40:1 [27]. This opens the possibility that another enzyme could perform in vivo the second reaction.…”

Section: Discussionmentioning

confidence: 99%

Effects of Water Availability in the Soil on Tropane Alkaloid Production in Cultivated Datura stramonium

Moreno-Pedraza¹,

Gabriel

Treutler

et al. 2019

Metabolites

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Background: different Solanaceae and Erythroxylaceae species produce tropane alkaloids. These alkaloids are the starting material in the production of different pharmaceuticals. The commercial demand for tropane alkaloids is covered by extracting them from cultivated plants. Datura stramonium is cultivated under greenhouse conditions as a source of tropane alkaloids. Here we investigate the effect of different levels of water availability in the soil on the production of tropane alkaloids by D. stramonium. Methods: We tested four irrigation levels on the accumulation of tropane alkaloids. We analyzed the profile of tropane alkaloids using an untargeted liquid chromatography/mass spectrometry method. Results: Using a combination of informatics and manual interpretation of mass spectra, we generated several structure hypotheses for signals in D. stramonium extracts that we assign as putative tropane alkaloids. Quantitation of mass spectrometry signals for our structure hypotheses across different anatomical organs allowed us to identify patterns of tropane alkaloids associated with different levels of irrigation. Furthermore, we identified anatomic partitioning of tropane alkaloid isomers with pharmaceutical applications. Conclusions: Our results show that soil water availability is an effective method for maximizing the production of specific tropane alkaloids for industrial applications.

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“…A. tanguticus may have developed the ability to produce and accumulate secondary metabolites to adapt to its environment. Accordingly, important enzymes such as the putrescine Nmethyltransferase and hyoscyamine 6 behydroxylase that participate in the biosynthetic pathway may be induced by local environment [17,18].…”

Section: Concentrations Of Tas From Different Geographic Originsmentioning

confidence: 99%

Multivariate statistical analysis of tropane alkaloids in Anisodus tanguticus (Maxim.) Pascher from different regions to trace geographical origins

Chen

Xiong

et al. 2022

AChrom

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Anisodus tanguticus (Maxim.) Pascher is an important Tibetan folk medicine and the source of tropane alkaloids (TAs) grown in Qinghai-Tibet Plateau. There are marked differences in quality of A. tanguticus from geographic areas. The aim of present research was to establish a method for the quantitative analysis of TAs coupled with chemometrics analysis to trace geographical origins. Qualitative analysis of TAs in A. tanguticus was carried out using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and quantitative analysis of TAs in different plant organs from different geographical origin was achieved. Contents of TAs were subjected to the principal component analysis, and orthogonal partial least-squares discriminant analysis. The contents of the three marker compounds (anisodamine, anisodine and atropine) in the roots and acrial parts of A. tanguticus were positive correlated and varied significantly from different geographical origins. Principal component analysis, and orthogonal partial least-squares discriminant analysis results showed excellent discrimination between different geographical origin of A. tanguticus. This study could provide comprehensive evaluation and further utilization of A. tanguticus resources.

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Isolation, expression and biochemical characterization of recombinant hyoscyamine-6β-hydroxylase from Brugmansia sanguinea – tuning the scopolamine production

Cited by 10 publications

References 23 publications

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Effects of Water Availability in the Soil on Tropane Alkaloid Production in Cultivated Datura stramonium

Multivariate statistical analysis of tropane alkaloids in Anisodus tanguticus (Maxim.) Pascher from different regions to trace geographical origins

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