An insight into conflux of metabolic traffic leading to picroside-I biosynthesis by tracking molecular time course changes in a medicinal herb, Picrorhiza kurroa

Kumar, Varun; Sharma, Neha; Shitiz, Kirti; Singh, Tiratha Raj; Tandon, Chanderdeep; Sood, Hemant; Chauhan, Rajinder Singh

doi:10.1007/s11240-015-0839-7

Cited by 16 publications

(13 citation statements)

References 18 publications

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“…The biosynthesis of P-I proceeds via non-mevalonate (MEP), mevalonate (MVA), shikimate/phenylpropanoid and iridoid pathways 5 . During the past years, numerous efforts have been carried out to shortlist candidate genes involved in P-I production through gene expression analyses performed under differential conditions of picrosides accumulation in P. kurroa 6 7 8 9 10 11 12 . Despite interesting cues obtained from these reports, no information is yet available on what mechanism controls the flux of P-I biosynthesis in P. kurroa .…”

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confidence: 99%

Exogenous feeding of immediate precursors reveals synergistic effect on picroside-I biosynthesis in shoot cultures of Picrorhiza kurroa Royle ex Benth

Kumar

Sharma

Sood

et al. 2016

Sci Rep

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In the current study, we asked how the supply of immediate biosynthetic precursors i.e. cinnamic acid (CA) and catalpol (CAT) influences the synthesis of picroside-I (P-I) in shoot cultures of P. kurroa. Our results revealed that only CA and CA+CAT stimulated P-I production with 1.6-fold and 4.2-fold, respectively at 2.5 mg/100 mL concentration treatment. Interestingly, feeding CA+CAT not only directed flux towards p-Coumaric acid (p-CA) production but also appeared to trigger the metabolic flux through both shikimate/phenylpropanoid and iridoid pathways by utilizing more of CA and CAT for P-I biosynthesis. However, a deficiency in the supply of either the iridoid or the phenylpropanoid precursor limits flux through the respective pathways as reflected by feedback inhibition effect on PAL and decreased transcripts expressions of rate limiting enzymes (DAHPS, CM, PAL, GS and G10H). It also appears that addition of CA alone directed flux towards both p-CA and P-I production. Based on precursor feeding and metabolic fluxes, a current hypothesis is that precursors from both the iridoid and shikimate/phenylpropanoid pathways are a flux limitation for P-I production in shoot cultures of P. kurroa plants. This work thus sets a stage for future endeavour to elevate production of P-I in cultured plant cells.

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confidence: 99%

Exogenous feeding of immediate precursors reveals synergistic effect on picroside-I biosynthesis in shoot cultures of Picrorhiza kurroa Royle ex Benth

Kumar

Sharma

Sood

et al. 2016

Sci Rep

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“…The higher expression level of genes encoding G6PI (1.67-fold), PFK (1.75-fold), ALD (3.60-fold) and ENO (2.73-fold) enzymes of glycolysis in roots might indicate that these genes contribute to atisine biosynthesis by producing higher levels of precursors for connecting pathways, viz. mevalonate, non-mevalonate (MEP) and serine biosynthetic pathways leading to their activation (Kumar et al 2015c ; Munoz-Bertomeu et al 2013 ). This was also supported by correlation analyses which showed significant positive correlations ( p < 0.05; p < 0.01; p < 0.001) between shortlisted transcripts of glycolysis, serine biosynthesis and diterpene biosynthesis (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…To enable this, quantitative real time-PCR (qRT-PCR) technique has emerged as a powerful tool that serves to target specific pathways over a wide range of experimental conditions and estimated the modulations in gene expression patters with amazed sensitivity and accuracy (Asters et al 2014 ; Kumar et al 2015c ).…”

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Molecular dissection of pathway components unravel atisine biosynthesis in a non-toxic Aconitum species, A. heterophyllum Wall

et al. 2016

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Aconitum heterophyllum is an important component for various herbal drug formulations due to the occurrence of non-toxic aconites including marker compound, atisine. Despite huge pharmacological potential, the reprogramming of aconites production is limited due to lack of understanding on their biosynthesis. To address this problem, we have proposed here the complete atisine biosynthetic pathway for the first time connecting glycolysis, MVA/MEP, serine biosynthesis and diterpene biosynthetic pathways. The transcript profiling revealed phosphorylated pathway as a major contributor towards serine production in addition to repertoire of genes in glycolysis (G6PI, PFK, ALD and ENO), serine biosynthesis (PGDH and PSAT) and diterpene biosynthesis (KO and KH) sharing a similar pattern of expression (2-4-folds) in roots compared to shoots vis-à-vis atisine content (0–0.37 %). Quantification of steviol and comparative analysis of shortlisted genes between roots of high (0.37 %) vs low (0.14 %) atisine content accessions further confirmed the route of atisine biosynthesis. The results showed 6-fold increase in steviol content and 3–62-fold up-regulation of all the selected genes in roots of high content accession ascertaining their association towards atisine production. Moreover, significant positive correlations were observed between selected genes suggesting their co-expression and crucial role in atisine biosynthesis. This study, thus, offers unprecedented opportunities to explore the selected candidate genes for enhanced production of atisine in cultivated plant cells.Electronic supplementary materialThe online version of this article (doi:10.1007/s13205-016-0417-7) contains supplementary material, which is available to authorized users.

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“…The study revealed contribution of MVA/MEP pathway genes (DXPS, ISPD, HMGR and PMK) for the first 20 days of plant growth with the major role of MEP pathway as compared to the MVA pathway. Conversely, geraniol-10-hydroxylase (G10H) and DAHPS contributed to P-I biosynthesis at 30 days of plant growth (Kumar et al 2015b). Further, application of hydrogen peroxide and abscisic acid up-regulated the genes, PkDXS, PkHDR, PkCOMT and PkIPPI in congruence with picrosides accumulation in P. kurroa ).…”

Section: Biosynthesis Of Iridoid Glycosidesmentioning

confidence: 98%

Biosynthesis and therapeutic implications of iridoid glycosides from Picrorhiza genus: the road ahead

Kumar

Chauhan

Tandon

2016

J. Plant Biochem. Biotechnol.

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Picrorhiza genus is emerging as an important paradigm for herbal drug formulations due to its versatile iridoid glycosides exhibition and robustness in the treatment of diverse infections including hepatic amoebiasis, cancer, malaria, ulcerative colitis and cerebral ischemia reperfusion injury. Owing to the superiority of these bioactivities, iridoid glycosides from Picrorhiza have become a hot research area over the years. A metabolic pathway for the formation of iridoid glycosides has been proposed. However, some enzymes and genes of this route are still unidentified and demand the enumeration of facilitating pathways contributing to the biosynthesis of iridoid glycosides. This review summarizes the current knowledge of all naturally occurring iridoid glycosides from Picrorhiza, their biosynthesis and pharmacological capabilities which could provide the insight into metabolic regulation and the basis for the development of new drugs.

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An insight into conflux of metabolic traffic leading to picroside-I biosynthesis by tracking molecular time course changes in a medicinal herb, Picrorhiza kurroa

Abstract: Picroside-I (P-

Cited by 16 publications

References 18 publications

Exogenous feeding of immediate precursors reveals synergistic effect on picroside-I biosynthesis in shoot cultures of Picrorhiza kurroa Royle ex Benth

Exogenous feeding of immediate precursors reveals synergistic effect on picroside-I biosynthesis in shoot cultures of Picrorhiza kurroa Royle ex Benth

Molecular dissection of pathway components unravel atisine biosynthesis in a non-toxic Aconitum species, A. heterophyllum Wall

Biosynthesis and therapeutic implications of iridoid glycosides from Picrorhiza genus: the road ahead

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