Increasing the Pace of New Discoveries in Tropane Alkaloid Biosynthesis

Jirschitzka, Jan; Dolke, Franziska; D’Auria, John C.

doi:10.1016/b978-0-12-408061-4.00002-x

Cited by 20 publications

(17 citation statements)

References 158 publications

(113 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This feature is found in TAs of species from all of the four major plant lineages known to produce these compounds (Jirschitzka et al, 2013). The esterification of TAs in E. coca was first suggested to proceed via CoA-activated thioesters (Leete et al, 1988), and two CoA-dependent acyltransferases involved in TA modification were purified from Datura stramonium, a member of the Solanaceae.…”

Section: Discussionmentioning

confidence: 99%

“…Some debate remains regarding whether these carbons are supplied via acetate, acetoacetate, or malonate (Leete et al, 1991;Robins et al, 1997). The oxobutanoic acid intermediate formed by this condensation then cyclizes to form a tropane intermediate called methylecgonone (Jirschitzka et al, 2013). In the penultimate biosynthetic step to cocaine, methylecgonone is reduced to form methylecgonine.…”

mentioning

confidence: 99%

See 1 more Smart Citation

The Last Step in Cocaine Biosynthesis Is Catalyzed by a BAHD Acyltransferase

et al. 2014

Self Cite

View full text Add to dashboard Cite

ORCID IDs: 0000-0003-1007-4700 (J.J.); 0000-0002-4865-3938 (J.C.D.).The esterification of methylecgonine (2-carbomethoxy-3b-tropine) with benzoic acid is the final step in the biosynthetic pathway leading to the production of cocaine in Erythoxylum coca. Here we report the identification of a member of the BAHD family of plant acyltransferases as cocaine synthase. The enzyme is capable of producing both cocaine and cinnamoylcocaine via the activated benzoyl-or cinnamoyl-Coenzyme A thioesters, respectively. Cocaine synthase activity is highest in young developing leaves, especially in the palisade parenchyma and spongy mesophyll. These data correlate well with the tissue distribution pattern of cocaine as visualized with antibodies. Matrix-assisted laser-desorption ionization mass spectral imaging revealed that cocaine and cinnamoylcocaine are differently distributed on the upper versus lower leaf surfaces. Our findings provide further evidence that tropane alkaloid biosynthesis in the Erythroxylaceae occurs in the above-ground portions of the plant in contrast with the Solanaceae, in which tropane alkaloid biosynthesis occurs in the roots.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

The Last Step in Cocaine Biosynthesis Is Catalyzed by a BAHD Acyltransferase

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…Tropane alkaloids are synthesized by several plant families, including the Erythroxylaceae, Proteaceae, and the Euphorbiaceae, but are particularly prevalent in the Atropa, Hyocyamus, Datura, Duboisia, and Brugmansia genera of the Solanaceae (Griffin and Lin, 2000;Jirschitzka et al, 2013). Extracts of these Solanaceous species have been used for centuries as medicinals, and the bioactive component, atropine, which is a racemic mixture of D-and L-hyoscyamine, together with scopolamine, are the active ingredients in modern therapeutics used to treat motion sickness, postoperative nausea, arrhythmia, and tremors associated with Parkinson's disease (Grynkiewicz and Gadzikowska, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…Putrescine is methylated by putrescine methyltransferase (PMT) to yield N-methylputrescine, which is subsequently converted into 4-methylaminobutanal by N-methylputrescine oxidase (Heim et al, 2007;Katoh et al, 2007;Biastoff et al, 2009). 4-Methylaminobutanal is postulated to undergo spontaneous cyclization to form an N-methyl-D 1 -pyrrolinium cation, which is ultimately converted to tropinone through an unknown mechanism (O'Connor, 2010;Jirschitzka et al, 2013). Tropinone represents a key branch point in the pathway (Hashimoto et al, 1992;Nakajima et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

View full text Add to dashboard Cite

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.

show abstract

“…There are more than 200 of these alkaloids, some of them with pharmacological interest due to their anticholinergic effects caused by binding to the muscarinic acetylcholine receptors at the nervous central system. These alkaloids are common in the Solanaceae and Erythroxylaceae families (Jirschitzka et al 2013). Examples of plants producing this type of alkaloids are members of the Datura genus, Atropa belladonna (the deadly nightshade), and Hyoscyamus niger (henbane).…”

Section: Plants Producing Tropane Alkaloidsmentioning

confidence: 99%

Application of Somatic Embryogenesis to Secondary Metabolite-Producing Plants

Vázquez‐Flota

Monforte‐González

Miranda-Ham

2016

Somatic Embryogenesis: Fundamental Aspects and Applications

View full text Add to dashboard Cite

Plants display an amazing biosynthetic capacity. To date, around 200,000 different chemical compounds have been isolated from them. Only a relatively few of these compounds are common to all plant species, since they are involved in basic or primary cell processes, such as energy metabolism. However, the broader plant chemical diversity corresponds to those compounds showing a restricted distribution among only a few taxonomically related species and which are not involved in primary metabolic pathways. These compounds are called secondary or specialized metabolites and they have important roles in numerous plant-environment interactions. Aside from these functions, secondary metabolites, and the plants bearing them, represent highly regarded commercial products given their pharmaceutical, flavoring, aromatic, coloring, and poisonous properties. In here, we present some selected examples of secondary metabolite-producing plants for which efficient protocols of somatic embryogenesis have been developed. The review covers mainly plants producing fine chemicals, used either in pharmaceutical or food industries. As shown, the development of somatic embryogenesis procedures could respond to two main goals: the genetic transformation of a given plant species, or the massive propagation of selected materials. Furthermore, the use of such protocols for the generation of diversity through indirect embryo formation is also presented.

show abstract

Increasing the Pace of New Discoveries in Tropane Alkaloid Biosynthesis

Cited by 20 publications

References 158 publications

The Last Step in Cocaine Biosynthesis Is Catalyzed by a BAHD Acyltransferase

The Last Step in Cocaine Biosynthesis Is Catalyzed by a BAHD Acyltransferase

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

Application of Somatic Embryogenesis to Secondary Metabolite-Producing Plants

Contact Info

Product

Resources

About