The formation of 3α&amp;#x2010; and 3β&amp;#x2010;acetoxytropanes by<i>Datura stramonium</i> transformed root cultures involves two acetyl&amp;#x2010;CoA&amp;#x2010;dependent acyltransferases

doi:10.1016/0014-5793(91)80887-9

Cited by 29 publications

(5 citation statements)

References 15 publications

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“…Although no enzymatic activity had been described, it is likely that an enzyme related to the cocaine synthase may be involved [59,60] in the formation of littorine. Littorine is rearranged via the littorine mutase/monooxygenase (CYP80F1; EC 1.6.2.4) to hyoscyamine aldehyde, which is subsequently reduced to the corresponding alcohol hyoscyamine [61].…”

Section: Ta Biosynthesis In Plantamentioning

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: Ta Biosynthesis In Plantamentioning

confidence: 99%

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

2019

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“…Robins [ 102 ] reported that different Datura acyltransferases act depending on whether the substrate is α- 10 or β- 10 . Individual acyltransferases also may have promiscuous substrate specificity.…”

Section: Alkaloids Of the Genus Datura —Tropane Alkaloidsmentioning

confidence: 99%

“…Individual acyltransferases also may have promiscuous substrate specificity. For example, tigloyl pseudotropine acyltransferase isolated from D. stramonium root cultures has the highest activity with tigloyl-CoA, but can also use acetyl, propionyl, isobutyroyl, and senecioyl-CoAs (among other aliphatic substrates) to acylate β- 10 , suggesting that the abundance of a given acyltropane may in part arise from competition between different substrates in the plant’s acyl-CoA (or other acyl donor) pool [ 102 , 103 ]. The aliphatic CoAs utilized by these enzymes are derived from short-chain (C 2 -C 5 ) carboxylic acids.…”

Section: Alkaloids Of the Genus Datura —Tropane Alkaloidsmentioning

confidence: 99%

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

Cinelli

Jones

2021

Molecules

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The genus Datura (Solanaceae) contains nine species of medicinal plants that have held both curative utility and cultural significance throughout history. This genus’ particular bioactivity results from the enormous diversity of alkaloids it contains, making it a valuable study organism for many disciplines. Although Datura contains mostly tropane alkaloids (such as hyoscyamine and scopolamine), indole, beta-carboline, and pyrrolidine alkaloids have also been identified. The tools available to explore specialized metabolism in plants have undergone remarkable advances over the past couple of decades and provide renewed opportunities for discoveries of new compounds and the genetic basis for their biosynthesis. This review provides a comprehensive overview of studies on the alkaloids of Datura that focuses on three questions: How do we find and identify alkaloids? Where do alkaloids come from? What factors affect their presence and abundance? We also address pitfalls and relevant questions applicable to natural products and metabolomics researchers. With both careful perspectives and new advances in instrumentation, the pace of alkaloid discovery—from not just Datura—has the potential to accelerate dramatically in the near future.

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“…Nevertheless, recent work challenges this long-standing speculation and propose the following roadmap: 3 β -Tropanol is esterified into 3 β -tigloyloxytropane (the key intermediate for the biosynthesis of calystegines), which undergoes demethylation and hydroxylation, followed by hydrolytic reactions, resulting in the production of calystegines 26 . Although Robins and colleagues reported that catalytic activities associated with 3 β -tropanol esterification occurred in Datura stramonium and A. belladonna in the 1990s 27 , 28 , the genes that encode acyltransferases responsible for the formation of 3 β -tropanol esters remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane

Zeng,

Liu,

Dong

et al. 2024

Nat Commun

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Solanaceous plants produce tropane alkaloids (TAs) via esterification of 3α- and 3β-tropanol. Although littorine synthase is revealed to be responsible for 3α-tropanol esterification that leads to hyoscyamine biosynthesis, the genes associated with 3β-tropanol esterification are unknown. Here, we report that a BAHD acyltransferase from Atropa belladonna, 3β-tigloyloxytropane synthase (TS), catalyzes 3β-tropanol and tigloyl-CoA to form 3β-tigloyloxytropane, the key intermediate in calystegine biosynthesis and a potential drug for treating neurodegenerative disease. Unlike other cytosolic-localized BAHD acyltransferases, TS is localized to mitochondria. The catalytic mechanism of TS is revealed through molecular docking and site-directed mutagenesis. Subsequently, 3β-tigloyloxytropane is synthesized in tobacco. A bacterial CoA ligase (PcICS) is found to synthesize tigloyl-CoA, an acyl donor for 3β-tigloyloxytropane biosynthesis. By expressing TS mutant and PcICS, engineered Escherichia coli synthesizes 3β-tigloyloxytropane from tiglic acid and 3β-tropanol. This study helps to characterize the enzymology and chemodiversity of TAs and provides an approach for producing 3β-tigloyloxytropane.

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The formation of 3α‐ and 3β‐acetoxytropanes byDatura stramonium transformed root cultures involves two acetyl‐CoA‐dependent acyltransferases

Cited by 29 publications

References 15 publications

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane

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The formation of 3α&#x2010; and 3β&#x2010;acetoxytropanes byDatura stramonium transformed root cultures involves two acetyl&#x2010;CoA&#x2010;dependent acyltransferases

Cited by 29 publications

References 15 publications

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Alkaloids of the Genus Datura: Review of a Rich Resource for Natural Product Discovery

Discovering a mitochondrion-localized BAHD acyltransferase involved in calystegine biosynthesis and engineering the production of 3β-tigloyloxytropane

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The formation of 3α‐ and 3β‐acetoxytropanes byDatura stramonium transformed root cultures involves two acetyl‐CoA‐dependent acyltransferases