Withanolide biosynthesis recruits both mevalonate and DOXP pathways of isoprenogenesis in Ashwagandha Withania somnifera L. (Dunal)

Chaurasiya, Narayan D.; Sangwan, Neelam S.; Sabir, Farzana; Misra, Laxminarain; Sangwan, Rajender Singh

doi:10.1007/s00299-012-1302-4

Cited by 98 publications

(80 citation statements)

References 38 publications

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“…This indicated that the two enzymes drive substrate conversion and triterpenoid biosynthesis directly, which corresponded with the observation that the MVA pathway synthesizes triterpenoids in the cytoplasmic matrix (Chaurasiya et al, 2012). By contrast, GlHMGR was predicted to be located in the secretory pathway because it harbors a 20aa signal peptide and has a three transmembrane region topological structure, which agreed with Campo's results (Campos et al, 1995).…”

Section: Cytological Characterization and Biochemical Functionsupporting

confidence: 85%

“…However, there are two distinct biosynthesis pathways; the mevalonate (MVA) pathway localized in the cytosol and the deoxyxylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate (DXP/MEP) pathway in plastids (Dewick, 2002;Aule et al, 2003;Chaurasiya et al, 2012). The former is predominant in fungal cells and has been studied extensively.…”

Section: Fig 1 Triterpenoid Biosynthetic Pathway In Ganoderma Cellsmentioning

confidence: 99%

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In silico Analysis of three Committed-Steps Involved in Triterpenoid Biosynthesis from Ganoderma lucidum

Shui¹,

Lan²,

Wei³

2016

American Journal of Biochemistry and Biotechnology

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Ganoderma lucidum is widely considered as one of the most valuable Traditional Chinese Medicines, with various bioactive constituents and pharmaceutical effects. Triterpenoids are important effective ingredients of G. lucidum, which are synthesized mainly through the mevalonate pathway. In this study, we aimed to characterize and analyze three committed-step enzymes of the mevalonate pathway, 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase (HMGR), Farnesyl Diphosphate Synthase (FPPS) and Squalene Synthase (SQS), using various bioinformatic tools and servers. As a results, the molecular structures and physicochemical properties of the proteins and their encoding genes (Glhmgr, Glfpps and Glsqs) were studied. The GlHMGR and GlFPPS proteins are localized in the cytosol and lack any transmembrane topological structures. By contrast, GlSQS enters the secretory pathway via its transit peptide and has three transmembrane helices. Phylogenetic analysis suggested that the three proteins could be classified into three large groups according to their significant functional association and genetic conservation. The secondary structures of the GlHMGR, GlFPPS and GlSQS comprise mainly α-helixes and random coils and the three tertiary structures were modeled successfully, including the identification of key motifs. Additionally, the expression levels of the three genes were compared on the basis of dbEST records. In conclusion, the results demonstrated that HMGR, FPPS and SQS from G. Lucidum have typical molecular structures and functions. In addition, we inferred that GlFPPS might be the perfect target for genetic engineering because of its position in a bottleneck step, as revealed by metabolic flux analysis.

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Section: Cytological Characterization and Biochemical Functionsupporting

confidence: 85%

Section: Fig 1 Triterpenoid Biosynthetic Pathway In Ganoderma Cellsmentioning

confidence: 99%

In silico Analysis of three Committed-Steps Involved in Triterpenoid Biosynthesis from Ganoderma lucidum

Shui¹,

Lan²,

Wei³

2016

American Journal of Biochemistry and Biotechnology

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“…Previous study indicated that withanolide biosynthesis probably involves 24-methylene cholesterol as a metabolic intermediate (Glotter 1991). 24-Methylene cholesterol originated from a triterpenoid (C 30 terpenoid) skeleton of isoprenoid pathway that operates via classical cytosolic mevalonate (MVA) pathway and/or plastidic 2-C-methyl-Derythritol-4-phosphate (MEP) pathway (Chaurasiya et al 2012). HMGR catalyzes irreversible conversion of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) into MVA that constitutes the key regulatory step of isoprenogenesis leading to the synthesis of IPP and its isomer, DMAPP, the progenitors of homologous series of isoprenoids (Chappell 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Most of the pharmacological activities of W. somnifera have been accredited to a few main withasteroids viz.withaferin A, withanolide A, etc. (Chakraborty et al 1974;Chaurasiya et al 2012). Metabolic origin of withanolides is from triterpenoid pathway, and both methyl-erythritol-4-phosphate and mevalonate pathways contribute to withanolide biosynthesis; however, the contribution of mevalonic acid (MVA) pathway is four times higher than the other one (Chaurasiya et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Metabolic shift from withasteroid formation to phenylpropanoid accumulation in cryptogein-cotransformed hairy roots of Withania somnifera (L.) Dunal

et al. 2014

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Cotransformed hairy roots containing a gene that encodes a fungal elicitor protein, β-cryptogein, were established in Withania somnifera, a medicinal plant widely used in Indian systems of medicine. To find out whether β-cryptogein protein endogenously elicits the pathway of withasteroid biosynthesis, withaferin A and withanolide A contents along with transcript accumulation of farnesyl pyrophosphate (FPP) synthase, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), and sterol glycosyltransferase (SGT) were analyzed in both cryptogein-cotransformed and normal hairy roots of W. somnifera. It was observed that the withaferin A and withanolide A contents were drastically higher in normal hairy roots than cryptogein-cotransformed ones. Similar trends were also observed on the levels of transcript accumulation. Subsequently, the enzyme activity of phenylalanine ammonia lyase (PAL), one of the key enzymes of phenylpropanoid pathway, was measured in both cryptogein-cotransformed and normal hairy roots of W. somnifera along with the levels of PAL transcript accumulation. Upliftment of PAL activity was observed in cryptogein-cotransformed hairy roots as compared to the normal ones, and the PAL expression also reflected a similar trend, i.e., enhanced expression in the cryptogein-cotransformed lines. Upliftment of wall-bound ferulic acid accumulation was also observed in the cryptogein-cotransformed lines, as compared to normal hairy root lines. Thus, the outcome of the above studies suggests a metabolic shift from withanolide accumulation to phenylpropanoid biosynthesis in cryptogein-cotransformed hairy roots of W. somnifera.

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“…Preliminary studies indicate that the isoprenoid precursors used in withanolide biosynthesis are synthesized through the mevalonate (MVA) pathway in the cytosol and the non-mevalonate [1-Deoxy-D-xylulose-5-phosphate (DOXP) or 2-C-methyl-D-erythritol-4-phosphate (MEP)] pathway in plastid (Sangwan et al 2008;Chaurasia et al 2012). After a series of reactions, isoprenoids generate 2, 3-oxidosqualene, which is the first branching point towards phytosterol and triterpene.…”

Section: Biosynthesis Routesmentioning

confidence: 99%

Phytochemistry and biosynthesis of δ-lactone withanolides

et al. 2015

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Withanolides are highly oxygenated natural products. These C 28 steroids with ergostane-based skeletons functionalized at C-22 and C-26 form sixmembered d-lactone rings. Withanolides containing a d-lactone side chain often occur in Solanaceae and have a variety of biological activities because of their complicated structures. Characteristic spectroscopic behaviors and biosynthesis of withanolides are conducive to their structural elucidation and ''biomimetic synthesis'', respectively. However, the last review to summarize their spectroscopic features and biosynthesis was in 1996. Since then, many withanolides with novel structures have been described by their spectra with biosynthesis investigated with many bioassays. This review surveys d-lactone withanolides and emphasizes their spectral features, configurations and biosynthetic genes. The period reviewed includes through January 2014. We also include phytochemical species.

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Withanolide biosynthesis recruits both mevalonate and DOXP pathways of isoprenogenesis in Ashwagandha Withania somnifera L. (Dunal)

Cited by 98 publications

References 38 publications

<i>In silico</i> Analysis of three Committed-Steps Involved in Triterpenoid Biosynthesis from <i>Ganoderma lucidum</i>

<i>In silico</i> Analysis of three Committed-Steps Involved in Triterpenoid Biosynthesis from <i>Ganoderma lucidum</i>

Metabolic shift from withasteroid formation to phenylpropanoid accumulation in cryptogein-cotransformed hairy roots of Withania somnifera (L.) Dunal

Phytochemistry and biosynthesis of δ-lactone withanolides

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