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binary stress induces an increase in indole alkaloid biosynthesis in catharanthus roseus.catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. in the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in c. roseus using proteomic technique. the contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in c. roseus were significantly increased under binary stress. proteomic analysis revealed that the abundanc ...201526284098
a novel terpenoid indole alkaloid derived from catharanthine via biotransformation by suspension-cultured cells of catharanthus roseus.although catharanthine (1) is well known as a biosynthetic precursor of the anticancer alkaloid, vinblastine, its alternative metabolic pathways are unclear.201526272394
phytochemica: a platform to explore phytochemicals of medicinal plants.plant-derived molecules (pdms) are known to be a rich source of diverse scaffolds that could serve as the basis for rational drug design. structured compilation of phytochemicals from traditional medicinal plants can facilitate prospection for novel pdms and their analogs as therapeutic agents. atropa belladonna, catharanthus roseus, heliotropium indicum, picrorhiza kurroa and podophyllum hexandrum are important himalayan medicinal plants, reported to have immense therapeutic properties against ...201526255307
the bhlh transcription factor bis1 controls the iridoid branch of the monoterpenoid indole alkaloid pathway in catharanthus roseus.plants make specialized bioactive metabolites to defend themselves against attackers. the conserved control mechanisms are based on transcriptional activation of the respective plant species-specific biosynthetic pathways by the phytohormone jasmonate. knowledge of the transcription factors involved, particularly in terpenoid biosynthesis, remains fragmentary. by transcriptome analysis and functional screens in the medicinal plant catharanthus roseus (madagascar periwinkle), the unique source of ...201526080427
isolation of catharanthus roseus (l.) g. don nuclei and measurement of rate of tryptophan decarboxylase gene transcription using nuclear run-on transcription assay.an accurate assessment of transcription 'rate' is often desired to describe the promoter activity. in plants, isolation of transcriptionally active nuclei and their subsequent use in nuclear run-on assays has been challenging and therefore limit an accurate measurement of gene transcription 'rate'. catharanthus roseus has emerged as a model medicinal plant as it exhibits an unsurpassed spectrum of chemodiversity, producing over 130 alkaloids through the terpenoid indole alkaloid (tia) pathway an ...201526024519
over-expression of catharanthus roseus tryptophan decarboxylase and strictosidine synthase in rol gene integrated transgenic cell suspensions of vinca minor.tryptophan decarboxylase (tdc) and strictosidine synthase (str) genes from catharanthus roseus have been successfully over-expressed in the rol gene integrated cell suspensions of v. minor. thirty seconds saat (sonication-assisted agrobacterium transformation) treatment of plant cell suspension with lba1119 having construct (<hpt-<tdc2-<str-gus>) generated three stable tdc + str over-expressing cell lines--pvg1, pvg2, and pvg3. the transgenes were confirmed by β-glucuronidase gus histochemical a ...201525106473
phytochemical genomics of the madagascar periwinkle: unravelling the last twists of the alkaloid engine.the madagascar periwinkle produces a large palette of monoterpenoid indole alkaloids (mias), a class of complex alkaloids including some of the most valuable plant natural products with precious therapeutical values. evolutionary pressure on one of the hotspots of biodiversity has obviously turned this endemic malagasy plant into an innovative alkaloid engine. catharanthus is a unique taxon producing vinblastine and vincristine, heterodimeric mias with complex stereochemistry, and also manufactu ...201525146650
effects of ambient and elevated co2 on growth, chlorophyll fluorescence, photosynthetic pigments, antioxidants, and secondary metabolites of catharanthus roseus (l.) g don. grown under three different soil n levels.catharanthus roseus l. plants were grown under ambient (375 ± 30 ppm) and elevated (560 ± 25 ppm) concentrations of atmospheric co2 at different rates of n supply (without supplemental n, 0 kg n ha(-1); recommended n, 50 kg n ha(-1); and double recommended n, 100 kg n ha(-1)) in open top chambers under field condition. elevated co2 significantly increased photosynthetic pigments, photosynthetic efficiency, and organic carbon content in leaves at recommended (rn) and double recommended n (drn), w ...201525304238
synthesis and characterization of palladium nanoparticles using catharanthus roseus leaf extract and its application in the photo-catalytic degradation.the potential effect of catharanthus roseus leaf extract for the formation of palladium nanoparticles and its application on dye degradation was discussed. the efficiency of c.roseus leaves are used as a bio-material for the first time as reducing agent. synthesized palladium nanoparticles were supported by uv-vis spectrometry, xrd, ft-ir and tem analysis. the secondary metabolites which are responsible for the formation of nanoparticles were identified by gc-ms. the results showed that effect o ...201525062057
investigation of the chemomarkers correlated with flower colour in different organs of catharanthus roseus using nmr-based metabolomics.flower colour is a complex phenomenon that involves a wide range of secondary metabolites of flowers, for example phenolics and carotenoids as well as co-pigments. biosynthesis of these metabolites, though, occurs through complicated pathways in many other plant organs. the analysis of the metabolic profile of leaves, stems and roots, for example, therefore may allow the identification of chemomarkers related to the final expression of flower colour.201524151112
optimisation of supercritical fluid extraction of indole alkaloids from catharanthus roseus using experimental design methodology--comparison with other extraction techniques.response surface modelling, using modde 6 software for design of experiments and optimisation, was applied to optimise supercritical fluid extraction (sfe) conditions for the extraction of indole alkaloids from the dried leaves of catharanthus roseus. the effects of pressure (200-400 bar), temperature (40-80 degrees c), modifier concentration (2.2-6.6 vol%) and dynamic extraction time (20-60 min) on the yield of alkaloids were evaluated. the extracts were analysed by high-performance liquid chro ...201517654538
enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, fusarium solani.ethanolic extract of a non-camptothecin producing plant, catharanthus roseus when added in the suspension culture of the endophyte fusarium solani known to produce camptothecin, resulted in enhanced production of camptothecin by 10.6-fold in comparison to that in control (2.8 μg/l). interestingly, addition of pure ethanol (up to 5% v/v) in the suspension culture of f. solani resulted in maximum enhancement in camptothecin production (up to 15.5-fold) from that obtained in control. in the presenc ...201525603728
antiplasmodial activity of medicinal plants from chhotanagpur plateau, jharkhand, india.the alarmingly increasing problem of drug resistance in treatment of malaria has led to an urgent need for identifying new anti-malarial drugs for both prophylaxis and chemotherapy.201525721804
the co-4 locus on chromosome pv08 contains a unique cluster of 18 cok-4 genes and is regulated by immune response in common bean.the common bean locus co - 4, traditionally referred to as an anthracnose-resistant gene, contains a cluster of predicted receptor-like kinases (cok-4 and crrlk1-like), and at least two of these kinases are co-regulated with the plant's basal immunity. genetic resistance to anthracnose, caused by the fungus colletotrichum lindemuthianum (sacc. and magnus) briosi and cavara, is conferred by major loci throughout the phaseolus vulgaris genome, named co. the complex co-4 locus was previously report ...201525805316
glucosylation of aroma chemicals and hydroxy fatty acids.to explore the utility of glycosyltransferases as novel biocatalysts, we isolated the glycosyltransferase genes caugt2 and sbugta1 from catharanthus roseus and starmerella bombicola, respectively and heterologously expressed them in escherichia coli. the purified recombinant proteins were assayed with a variety of small molecule substrates. carvacrol and its phenol isomer thymol are efficiently glucosylated by caugt2. the vmax/km ratios show that caugt2 exhibits the highest specificity towards c ...201526481830
antimicrobial potentials of catharanthus roseus by disc diffusion assay.the present research work investigates the in vitro antimicrobial activity of different solvent extracted samples from the aerial parts (stem, leaf, fruit and flower) of c. roseus against different microbial species using disc diffusion assay at two different concentrations of 1 and 2 mg disc-1. hexane extracted samples inhibited the growth of all tested microbial strains except s. typhi. similarly, ethyl acetate extracted samples was effective to control the activity of all the tested microbial ...201526004715
completion of the seven-step pathway from tabersonine to the anticancer drug precursor vindoline and its assembly in yeast.antitumor substances related to vinblastine and vincristine are exclusively found in the catharanthus roseus (madagascar periwinkle), a member of the apocynaceae plant family, and continue to be extensively used in cancer chemotherapy. although in high demand, these valuable compounds only accumulate in trace amounts in c. roseus leaves. vinblastine and vincristine are condensed from the monoterpenoid indole alkaloid (mia) precursors catharanthine and vindoline. although catharanthine biosynthes ...201525918424
de novo production of the plant-derived alkaloid strictosidine in yeast.the monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. there are ∼3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. the diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. reconstitution of biosynthetic pa ...201525675512
an endophytic fungus, talaromyces radicus, isolated from catharanthus roseus, produces vincristine and vinblastine, which induce apoptotic cell death.endophytic fungi isolated from catharanthus roseus were screened for the production of vincristine and vinblastine. twenty-two endophytic fungi isolated from various tissues of c. roseus were characterized taxonomically by sequence analysis of the internal transcribed spacer (its) region of rdna and grouped into 10 genera: alternaria, aspergillus, chaetomium, colletotrichum, dothideomycetes, eutypella, eutypa, flavodon, fusarium and talaromyces. the antiproliferative activity of these fungi was ...201526697875
virus-induced gene silencing in catharanthus roseus by biolistic inoculation of tobacco rattle virus vectors.catharanthus roseus constitutes the unique source of several valuable monoterpenoid indole alkaloids, including the antineoplastics vinblastine and vincristine. these alkaloids result from a complex biosynthetic pathway encompassing between 30 and 50 enzymatic steps whose characterisation is still underway. the most recent identifications of genes from this pathway relied on a tobacco rattle virus-based virus-induced gene silencing (vigs) approach, involving an agrobacterium-mediated inoculation ...201526284695
ornamental exterior versus therapeutic interior of madagascar periwinkle (catharanthus roseus): the two faces of a versatile herb.catharanthus roseus (l.) known as madagascar periwinkle (mp) is a legendary medicinal plant mostly because of possessing two invaluable antitumor terpenoid indole alkaloids (tias), vincristine and vinblastine. the plant has also high aesthetic value as an evergreen ornamental that yields prolific blooms of splendid colors. the plant possesses yet another unique characteristic as an amiable experimental host for the maintenance of the smallest bacteria found on earth, the phytoplasmas and spiropl ...201525667940
co-overexpression of geraniol-10-hydroxylase and strictosidine synthase improves anti-cancer drug camptothecin accumulation in ophiorrhiza pumila.camptothecin (cpt) belongs to a group of monoterpenoidindole alkaloids (tias) and its derivatives such as irinothecan and topothecan have been widely used worldwide for the treatment of cancer, giving rise to rapidly increasing market demands. genes from catharanthus roseus encoding strictosidine synthase (str) and geraniol 10-hydroxylase (g10h), were separately and simultaneously introduced into ophiorrhiza pumila hairy roots. overexpression of individual g10h (g lines) significantly improved c ...201525648209
evaluation of antimicrobial activity of extracts of in vivo and in vitro grown vinca rosea l. (catharanthus roseus) against pathogens.the antimicrobial activity of vinca rosea was evaluated against pathogenic bacterial strains (bacillus subtilis, b. licheniformis and azotobacter sp.) and fungal strains (asprgillus niger, alternaria solani and rhizopus oryzae) using agar well diffusion method. methanolic extracts of in vivo leaf, in vitro leaf, in vitro calluses of leaf, nodal and fruit explants were used and exhibited antimicrobial activity as indicated by minimum inhibitory concentration (mic). in vitro extracts showed better ...201526004716
morphogenetic and chemical stability of long-term maintained agrobacterium-mediated transgenic catharanthus roseus plants.transgenic catharanthus roseus plants (transgenic dhawal [dt] and transgenic nirmal [nt]) obtained from the agrobacterium tumefaciens and agrobacterium rhizognenes-mediated transformations, respectively, have been maintained in vitro for 5 years. plants were studied at regular intervals for various parameters such as plant height, leaf size, multiplication rate, alkaloid profile and presence of marker genes. dt plant gradually lost the gus gene expression and it was not detected in the fifth yea ...201525102992
screening and kinetic studies of catharanthine and ajmalicine accumulation and their correlation with growth biomass in catharanthus roseus hairy roots.context catharanthus roseus (l.) g. don (apocynaceae) is still one of the most important sources of terpene indole alkaloids including anticancer and hypertensive drugs as vincristine and vinblastine. these final compounds have complex pathway and many enzymes are involved in their biosynthesis. indeed, ajmalicine and catharanthine are important precursors their increase can lead to enhance levels of molecules of interest. objective this study aims at selecting the highest yield of hairy root li ...201626983347
antibacterial activity of six medicinal cameroonian plants against gram-positive and gram-negative multidrug resistant phenotypes.infectious diseases due to multidrug-resistant bacteria are one of the causes of treatment failures contributing to an increase in mortality and/or morbidity. in this study, we evaluated the antibacterial potential of different parts of six medicinal plants namely alstonia boonei, ageratum conyzoides, croton macrostachys, cassia obtusifolia, catharanthus roseus and paullinia pinnata against a panel of 36 multi-drug resistant (mdr) gram-negative and gram-positive bacteria.201627724917
evaluation of the larvicidal efficacy of five indigenous weeds against an indian strain of dengue vector, aedes aegypti l. (diptera: culicidae).background and objectives. aedes aegypti, dengue fever mosquito, is primarily associated with the transmission of dengue and chikungunya in tropical and subtropical regions of the world. the present investigations were carried out to assess the larvicidal efficiency of five indigenous weeds against ae. aegypti. methods. the 1,000 ppm hexane and ethanol extracts prepared from the leaves and stem of five plants (achyranthes aspera, cassia occidentalis, catharanthus roseus, lantana camara, and xant ...201626941996
cholinesterase inhibitor (altenuene) from an endophytic fungus alternaria alternata: optimization, purification and characterization.the aim of this study was to screen endophytic fungi isolated from vinca rosea for their potential to produce acetylcholinesterase (ache) inhibitors.201627248836
function of ap2/erf transcription factors involved in the regulation of specialized metabolism in ophiorrhiza pumila revealed by transcriptomics and metabolomics.the hairy roots (hr) of ophiorrhiza pumila produce camptothecin (cpt), a monoterpenoid indole alkaloid used as a precursor in the synthesis of chemotherapeutic drugs. o. pumila hr culture is considered as a promising alternative source of cpt, however, the knowledge about the biosynthetic pathway and regulatory mechanism is still limited. in this study, five genes that encode ap2/erf transcription factors, namely operf1-operf5, were isolated from hr of o. pumila. phylogenetic analysis of ap2/erf ...201628018397
silencing the transcriptional repressor, zct1, illustrates the tight regulation of terpenoid indole alkaloid biosynthesis in catharanthus roseus hairy roots.the catharanthus roseus plant is the source of many valuable terpenoid indole alkaloids (tias), including the anticancer compounds vinblastine and vincristine. transcription factors (tfs) are promising metabolic engineering targets due to their ability to regulate multiple biosynthetic pathway genes. to increase tia biosynthesis, we elicited the tia transcriptional activators (orcas and other unidentified tfs) with the plant hormone, methyl jasmonate (mj), while simultaneously silencing the expr ...201627467510
potent antioxidant properties of rolb-transformed catharanthus roseus (l.) g. don.free radicals play an important role in pathological processes such as aging and developing cancer; hence, natural products inhibit free radical production, and can play an important role in preventing diseases. we aimed to evaluate the scavenging activity of free radicals, reducing power, inhibition of lipid peroxidation and malondialdehyde (mda) formation, and the antioxidant composition of rolb-transformed hairy roots and leaf callus of catharanthus roseus. hairy roots of the catharanthus ros ...201627642325
molecular interaction of selected phytochemicals under the charged environment of plasmodium falciparum chloroquine resistance transporter (pfcrt) model.phytochemicals of catharanthus roseus linn. and tylophora indica have been known for their inhibition of malarial parasite, plasmodium falciparum in cell culture. resistance to chloroquine (cq), a widely used antimalarial drug, is due to the cq resistance transporter (crt) system. the present study deals with computational modeling of plasmodium falciparum chloroquine resistance transporter (pfcrt) protein and development of charged environment to mimic a condition of resistance. the model of pf ...201625783783
differential expression of spiroplasma citri surface protein genes in the plant and insect hosts.spiroplasma citri is a cell wall-less, plant pathogenic bacteria that colonizes two distinct hosts, the leafhopper vector and the host plant. given the absence of a cell wall, surface proteins including lipoproteins and transmembrane polypeptides are expected to play key roles in spiroplasma/host interactions. important functions in spiroplasma/insect interactions have been shown for a few surface proteins such as the major lipoprotein spiralin, the transmembrane s. citri adhesion-related protei ...201627005573
prequels to synthetic biology: from candidate gene identification and validation to enzyme subcellular localization in plant and yeast cells.natural compounds extracted from microorganisms or plants constitute an inexhaustible source of valuable molecules whose supply can be potentially challenged by limitations in biological sourcing. the recent progress in synthetic biology combined to the increasing access to extensive transcriptomics and genomics data now provide new alternatives to produce these molecules by transferring their whole biosynthetic pathway in heterologous production platforms such as yeasts or bacteria. while the g ...201627480687
engineering of a nepetalactol-producing platform strain of saccharomyces cerevisiae for the production of plant seco-iridoids.the monoterpene indole alkaloids (mias) are a valuable family of chemicals that include the anticancer drugs vinblastine and vincristine. these compounds are of global significance-appearing on the world health organization's list of model essential medicines-but remain exorbitantly priced due to low in planta levels. chemical synthesis and genetic manipulation of mia producing plants such as catharanthus roseus have so far failed to find a solution to this problem. synthetic biology holds a pot ...201626981892
endophytic filamentous fungi from a catharanthus roseus: identification and its hydrolytic enzymes.this paper reported on the various filamentous fungi strains that were isolated from a wild grown catharanthus roseus. based on the morphological characteristics and molecular technique through a polymerase chain reaction and dna sequencing method using internal transcribed spacer (its), these fungi had been identified as a colletotrichum sp., macrophomina phaseolina, nigrospora sphaerica and fusarium solani. the ultrastructures of spores and hyphae were observed under a scanning electron micros ...201627275114
cell-specific localization of alkaloids in catharanthus roseus stem tissue measured with imaging ms and single-cell ms.catharanthus roseus (l.) g. don is a medicinal plant well known for producing antitumor drugs such as vinblastine and vincristine, which are classified as terpenoid indole alkaloids (tias). the tia metabolic pathway in c. roseus has been extensively studied. however, the localization of tia intermediates at the cellular level has not been demonstrated directly. in the present study, the metabolic pathway of tia in c. roseus was studied with two forefront metabolomic techniques, that is, imaging ...201627001858
engineering overexpression of orca3 and strictosidine glucosidase in catharanthus roseus hairy roots increases alkaloid production.catharanthus roseus produces many pharmaceutically important terpenoid indole alkaloids (tias) such as vinblastine, vincristine, ajmalicine, and serpentine. past metabolic engineering efforts have pointed to the tight regulation of the tia pathway and to multiple rate-limiting reactions. transcriptional regulator orca3 (octadecanoid responsive catharanthus ap2-domain protein), activated by jasmonic acid, plays a central role in regulating the tia pathway. in this study, overexpressing orca3 unde ...201626351111
rapid and simultaneous determination of five vinca alkaloids in catharanthus roseus and human serum using trilinear component modeling of liquid chromatography-diode array detection data.a novel chemometrics-assisted high performance liquid chromatography method coupled with diode array detector (hplc-dad) was proposed for the simultaneous determination of vincristine (vcr), vinblastine (vlb), vindoline (vdl), catharanthine (cat) and yohimbine (yhb) in catharanthus roseus (c. roseus) and human serum samples. with the second-order advantage of the alternating trilinear decomposition (atld) method, the resolution and rapid determination of five components of interest in complex ma ...201626321366
transcriptional regulation and transport of terpenoid indole alkaloid in catharanthus roseus: exploration of new research directions.as one of the model medicinal plants for exploration of biochemical pathways and molecular biological questions on complex metabolic pathways, catharanthus roseus synthesizes more than 100 terpenoid indole alkaloids (tias) used for clinical treatment of various diseases and for new drug discovery. given that extensive studies have revealed the major metabolic pathways and the spatial-temporal biosynthesis of tia in c. roseus plant, little is known about subcellular and inter-cellular trafficking ...201628036025
industrial case study on alkaloids purification by ph-zone refining centrifugal partition chromatography.the industrial potential of ph-zone refining centrifugal partition chromatography has been evaluated by studying the purification of pharmaceutical ingredients at the pilot scale. for the first time, a scale up methodology based on both column capacity and mass transfer efficiency as invariants was developed. the purification of catharanthine and vindoline from an industrial crude extract of aerial parts of catharanthus roseus, was used as a case of study. toluene/ch3cn/water (4/1/5, v/v/v) was ...201627816224
structural determinants of reductive terpene cyclization in iridoid biosynthesis.the carbon skeleton of ecologically and pharmacologically important iridoid monoterpenes is formed in a reductive cyclization reaction unrelated to canonical terpene cyclization. here we report the crystal structure of the recently discovered iridoid cyclase (from catharanthus roseus) bound to a mechanism-inspired inhibitor that illuminates substrate binding and catalytic function of the enzyme. key features that distinguish iridoid synthase from its close homolog progesterone 5β-reductase are h ...201626551396
role and functioning of bhlh transcription factors in jasmonate signalling.plant growth, development and interaction with the environment involve the action of multiple phytohormones. transcription factors (tfs) of diverse families play essential roles in the signalling cascades triggered by the perception of a particular hormone. tfs may act alone or in a combinatorial fashion with other tfs, and may act specifically in a single hormonal signalling cascade or as signalling hubs for multiple hormones. in the signalling cascades triggered by the phytohormone jasmonate ( ...201627927998
game9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway.steroidal glycoalkaloids (sgas) are cholesterol-derived molecules produced by solanaceous species. they contribute to pathogen defence but are toxic to humans and considered as anti-nutritional compounds. here we show that glycoalkaloid metabolism 9 (game9), an apetala2/ethylene response factor, related to regulators of alkaloid production in tobacco and catharanthus roseus, controls sga biosynthesis. game9 knockdown and overexpression in tomato and potato alters expression of sgas and upstream ...201626876023
a simple and rapid hplc-dad method for simultaneously monitoring the accumulation of alkaloids and precursors in different parts and different developmental stages of catharanthus roseus plants.a rapid and simple reversed phase liquid chromatographic system has been developed for simultaneous analysis of terpenoid indole alkaloids (tias) and their precursors. this method allowed separation of 11 compounds consisting of eight tias (ajmalicine, serpentine, catharanthine, vindoline, vindolinine, vincristine, vinblastine, and anhydrovinblastine) and three related precursors i.e., tryptophan, tryptamine and loganin. the system has been applied for screening the tias and precursors in cathar ...201626854826
a picrinine n-methyltransferase belongs to a new family of γ-tocopherol-like methyltransferases found in medicinal plants that make biologically active monoterpenoid indole alkaloids.members of the apocynaceae plant family produce a large number of monoterpenoid indole alkaloids (mias) with different substitution patterns that are responsible for their various biological activities. a novel n-methyltransferase involved in the vindoline pathway in catharanthus roseus showing distinct similarity to γ-tocopherol c-methyltransferases was used in a bioinformatic screen of transcriptomes from vinca minor, rauvolfia serpentina, and c. roseus to identify 10 γ-tocopherol-like n-methy ...201626848097
analytical and fluorimetric methods for the characterization of the transmembrane transport of specialized metabolites in plants.the characterization of membrane transport of specialized metabolites is essential to understand their metabolic fluxes and to implement metabolic engineering strategies towards the production of increased levels of these valuable metabolites. here, we describe a set of procedures to isolate tonoplast membranes, to check their purity and functionality, and to characterize their transport properties. transport is assayed directly by hplc analysis and quantification of the metabolites actively acc ...201626843171
application of natural deep eutectic solvents to the extraction of anthocyanins from catharanthus roseus with high extractability and stability replacing conventional organic solvents.natural deep eutectic solvents (nades) have attracted a great deal of attention in recent times as promising green media. they are generally composed of neutral, acidic or basic compounds that form liquids of high viscosity when mixed in certain molar ratio. despite their potential, viscosity and acid or basic nature of some ingredients may affect the extraction capacity and stabilizing ability of the target compounds. to investigate these effects, extraction with a series of nades was employed ...201626822320
understanding crrlk1l function: cell walls and growth control.to develop successfully in an ever-changing environment, it is essential for plants to monitor and control their growth. therefore, cell expansion is carefully regulated to establish correct cell shape and size. in this review, we explore the role of the catharanthus roseus receptor-like kinase (crrlk1l) subfamily as regulators of cell expansion. recently, the downstream signalling events of individual crrlk1l pathways were discovered, implicating known modulators of cell expansion, such as reac ...201626778775
apocynaceae species with antiproliferative and/or antiplasmodial properties: a review of ten genera.apocynaceae is a large family of tropical trees, shrubs and vines with most species producing white latex. major metabolites of species are triterpenoids, iridoids, alkaloids and cardenolides, which are known for a wide range of biological and pharmacological activities such as cardioprotective, hepatoprotective, neuroprotective, anti-inflammatory, anticancer and antimalarial properties. prompted by their anticancer and antimalarial properties, the current knowledge on ten genera (allamanda, als ...201627417173
the basic helix-loop-helix transcription factor bis2 is essential for monoterpenoid indole alkaloid production in the medicinal plant catharanthus roseus.monoterpenoid indole alkaloids (mias) are produced as plant defence compounds. in the medicinal plant catharanthus roseus, they comprise the anticancer compounds vinblastine and vincristine. the iridoid (monoterpenoid) pathway forms one of the two branches that feed mia biosynthesis and its activation is regulated by the transcription factor (tf) basic helix-loop-helix (bhlh) iridoid synthesis 1 (bis1). here, we describe the identification and characterisation of bis2, a jasmonate (ja)-responsiv ...201627342401
clade iva basic helix-loop-helix transcription factors form part of a conserved jasmonate signaling circuit for the regulation of bioactive plant terpenoid biosynthesis.plants produce many bioactive, specialized metabolites to defend themselves when facing various stress situations. their biosynthesis is directed by a tightly controlled regulatory circuit that is elicited by phytohormones such as jasmonate (ja). the basic helix-loop-helix (bhlh) transcription factors (tfs) bhlh iridoid synthesis 1 (bis1) and triterpene saponin activating regulator (tsar) 1 and 2, from catharanthus roseus and medicago truncatula, respectively, all belong to clade iva of the bhlh ...201627694525
class ii cytochrome p450 reductase governs the biosynthesis of alkaloids.expansion of the biosynthesis of plant specialized metabolites notably results from the massive recruitment of cytochrome p450s that catalyze multiple types of conversion of biosynthetic intermediates. for catalysis, p450s require a two-electron transfer catalyzed by shared cytochrome p450 oxidoreductases (cprs), making these auxiliary proteins an essential component of specialized metabolism. cpr isoforms usually group into two distinct classes with different proposed roles, namely involvement ...201627688619
a polymorphic (ga/ct)n- ssr influences promoter activity of tryptophan decarboxylase gene in catharanthus roseus l. don.simple sequence repeats (ssrs) of polypurine-polypyrimidine type motifs occur very frequently in the 5' flanks of genes in plants and have recently been implicated to have a role in regulation of gene expression. in this study, 2 accessions of catharanthus roseus having (ct)8 and (ct)21 varying motifs in the 5'utr of tryptophan decarboxylase (tdc) gene, were investigated for its role in regulation of gene expression. extensive tdc gene expression analysis in the 2 accessions was carried out both ...201627623355
conserved roles of crrlk1l receptor-like kinases in cell expansion and reproduction from algae to angiosperms.receptor-like kinases (rlks) are regulators of plant development through allowing cells to sense their extracellular environment. they facilitate detection of local endogenous signals, in addition to external biotic and abiotic stimuli. the catharanthus roseus rlk1-like (crrlk1l) protein kinase subfamily, which contains feronia, plays a central role in regulating fertilization and in cell expansion mechanisms such as cell elongation and tip growth, as well as having indirect links to plant-patho ...201627621737
generous hosts: what makes madagascar periwinkle (catharanthus roseus) the perfect experimental host plant for fastidious bacteria?although much attention has been paid to the metabolism and biosynthesis of monoterpene alkaloids in catharanthus roseus, its value as an experimental host for a variety of agriculturally and economically important phytopathogenic bacteria warrants further study. in the present study, we evaluated the chemical composition of the phloem and xylem saps of c. roseus to infer the nutritional requirements of phloem- and xylem-limited phytopathogens. periwinkle phloem sap consisted of a rich mixture o ...201627620272
differential network analysis reveals evolutionary complexity in secondary metabolism of rauvolfia serpentina over catharanthus roseus.comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. rauvolfia serpentina and catharanthus roseus, both members of apocyanacae family, are reported to have remedial properties against multiple diseases. despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized met ...201627588023
fungal vincristine from eutypella spp - crp14 isolated from catharanthus roseus induces apoptosis in human squamous carcinoma cell line -a431.catharanthus roseus, a medicinal plant, is known to produce secondary metabolites, vincristine and vinblastine, which are terpenoid indole alkaloids. previously we have reported that eutypella spp - crp14 isolated from stem cutting of this plant had shown significant antiproliferative activity when tested in vitro against hela cell line. the present study was conducted to identify the anticancer compound responsible for the anti-proliferative activity of the fungal extract and to evaluate its in ...201627550200
biosynthesis of silver nanoparticles from catharanthus roseus leaf extract and assessing their antioxidant, antimicrobial, and wound-healing activities.biosynthesis of silver nanoparticles (agnps) from catharanthus roseus leaf extract was carried out, and their characterization, as well as antioxidant, antimicrobial, and wound-healing activities were evaluated. color change, uv-vis spectrum, xrd, ftir, and afm assessments supported the biosynthesis and characterization of agnps. the synthesized agnps showed strong in vitro antioxidant and antimicrobial activities against various pathogens. the in vivo assessment of wound healing in agnps-treate ...201627534756
artemisinic acid serves as a novel orca3 inducer to enhance biosynthesis of terpenoid indole alkaloids in catharanthus roseus cambial meristematic cells.to investigate the effect of artemisinic acid (aa) on improving the production of terpenoid indole alkaloids (tias) of catharanthus roseus cambial meristematic cells (cmcs), feeding aa to c. roseus cmcs caused 2.35-fold and 2.51-fold increases in the production of vindoline and catharanthine, respectively, compared with those of the untreated cmcs. qrt-pcr experiments showed that aa resulted in a 1.36-8.52 fold increase in the transcript levels of several related genes, including octadecanoid-de ...201627534099
structural investigation of heteroyohimbine alkaloid synthesis reveals active site elements that control stereoselectivity.plants produce an enormous array of biologically active metabolites, often with stereochemical variations on the same molecular scaffold. these changes in stereochemistry dramatically impact biological activity. notably, the stereoisomers of the heteroyohimbine alkaloids show diverse pharmacological activities. we reported a medium chain dehydrogenase/reductase (mdr) from catharanthus roseus that catalyses formation of a heteroyohimbine isomer. here we report the discovery of additional heteroyo ...201627418042
the combined effects of ethylene and meja on metabolic profiling of phenolic compounds in catharanthus roseus revealed by metabolomics analysis.phenolic compounds belong to a class of secondary metabolites and are implicated in a wide range of responsive mechanisms in plants triggered by both biotic and abiotic elicitors. in this study, we approached the combinational effects of ethylene and meja (methyl jasmonate) on phenolic compounds profiles and gene expressions in the medicinal plant catharanthus roseus. in virtue of a widely non-targeted metabolomics method, we identified a total of 34 kinds of phenolic compounds in the leaves, co ...201627375495
isolation of cells specialized in anticancer alkaloid metabolism by fluorescence-activated cell sorting.plant specialized metabolism often presents a complex cell-specific compartmentation essential to accomplish the biosynthesis of valuable plant natural products. hence, the disclosure and potential manipulation of such pathways may depend on the capacity to isolate and characterize specific cell types. catharanthus roseus is the source of several medicinal terpenoid indole alkaloids, including the low-level anticancer vinblastine and vincristine, for which the late biosynthetic steps occur in sp ...201627356972
ethylene-induced vinblastine accumulation is related to activated expression of downstream tia pathway genes in catharanthus roseus.we selected different concentrations of ethephon, to stress c. roseus. we used qrt-pcr and hplc followed by pca to obtain comprehensive profiling of the vinblastine biosynthesis in response to ethephon. based on our findings, the results showed that the high concentration of ethephon had a positive effect at both transcriptional and metabolite level. meanwhile, there was a remarkable decrease of hydrogen peroxide content and a promoted peroxidase activity in leaves. the loading plot combination ...201627314017
'candidatus phytoplasma hispanicum', a novel taxon associated with mexican periwinkle virescence disease of catharanthus roseus.mexican periwinkle virescence (mpv) phytoplasma was originally discovered in diseased plants of madagascar periwinkle (catharanthus roseus) in yucatán, mexico. on the basis of results from rflp analysis of pcr-amplified 16s rrna gene sequences, strain mpv was previously classified as the first known member of phytoplasma group 16srxiii, and a new subgroup (16srxiii-a) was established to accommodate mpv phytoplasma. phylogenetic analysis of 16s rrna gene sequences indicated that strain mpv repres ...201627266266
fungal endophytes of catharanthus roseus enhance vindoline content by modulating structural and regulatory genes related to terpenoid indole alkaloid biosynthesis.not much is known about the mechanism of endophyte-mediated induction of secondary metabolite production in catharanthus roseus. in the present study two fungal endophytes, curvularia sp. catdlf5 and choanephora infundibulifera catdlf6 were isolated from the leaves of the plant that were found to enhance vindoline content by 229-403%. the isolated endophytes did not affect the primary metabolism of the plant as the maximum quantum efficiency of psii, net co2 assimilation, plant biomass and starc ...201627220774
induction of apoptosis in human leukemia cells through an intrinsic pathway by cathachunine, a unique alkaloid isolated from catharanthus roseus.catharanthus roseus (l.) g. don consists of a range of dimeric indole alkaloids with significant antitumor activities. these alkaloids have been found to possess apoptosis-inducing activity against tumor cells in vitro and in vivo mediated by nuclear factor kappa-light-chain-enhancer of activated b cells (nf-κb) and c-jun n-terminal kinase (jnk) pathways, in which dna damage and mitochondrial dysfunction play important roles. in this study, a unique bisindole alkaloid named cathachunine, along w ...201627161405
examining the transcriptional response of overexpressing anthranilate synthase in the hairy roots of an important medicinal plant catharanthus roseus by rna-seq.clinically important anti-cancer drugs vinblastine and vincristine are solely synthesized by the terpenoid indole alkaloid (tia) pathway in catharanthus roseus. anthranilate synthase (as) is a rate-limiting enzyme in the tia pathway. the transgenic c. roseus hairy root line overexpressing a feedback insensitive asα subunit under the control of an inducible promoter and the asβ subunit constitutively was previously created for the overproduction of tias. however, both increases and decreases in t ...201627154243
beneficial behavior of nitric oxide in copper-treated medicinal plants.despite numerous reports implicating nitric oxide (no) in the environmental-stress responses of plants, the specific metabolic and ionic mechanisms of no-mediated adaptation to metal stress remain unclear. here, the impacts of copper (cu) and no donor (snp, 50μm) alone or in combination on the well-known medicinal plant catharanthus roseus l. were investigated. our results showed that cu markedly increased cu(2+) accumulation, decreased no production, and disrupted mineral equilibrium and proton ...201627131454
correction: an endophytic fungus, talaromyces radicus, isolated from catharanthus roseus, produces vincristine and vinblastine, which induce apoptotic cell death. 201627046169
studies on production of ajmalicine in shake flasks by multiple shoot cultures of catharanthus roseus.the effects of different concentrations of indole-3-acetic acid (iaa) and benzyladenine (ba) on production of ajmalicine by multiple shoot cultures of catharanthus roseus (c. roseus) were studied. by supplementing murashige and skoog's (ms) medium with a high concentration of iaa (11.42 microm) and a low concentration of ba (2.22 microm), shoot cultures accumulated high levels of ajmalicine. when culture medium was fortified with a low concentration of iaa (2.85 microm) and a high concentration ...201612790683
responses of transformed catharanthus roseus roots to femtomolar concentrations of salicylic acid.catharanthus roseus transformed roots were cultured in the presence of salicylic acid (sa) at concentrations between 0.1 fm and 100 pm and the effect on root growth was evaluated. significant morphological changes in the lateral roots were recorded on day two in the sa treatment. presence of sa increased root cap size and caused the appearance of lateral roots closer to the root tip. the bioassay was sensitive enough to allow testing of low concentrations of other growth regulators that may affe ...201617544287
alkaloid metabolism in wounded catharanthus roseus seedlings.the effect of mechanical wounding on alkaloid metabolism was analyzed in catharanthus roseus seedlings. wounding induced an increase in ajmalicine accumulation, whereas catharanthine remained unaffected. a positive dual effect on vindoline was noticed. short and mid-term effects were detected between 12 and 24 h after mechanical damage was inflicted, and apparently resulted from the accelerated transformation of the tabersonine intermediaries to vindoline. long-term effects involved a generalize ...201615331091
cytotoxic effect of erythroxylum suberosum combined with radiotherapy in head and neck cancer cell lines.the mouth and oropharynx cancer is the 6th most common type of cancer in the world. the treatment may involve surgery, chemotherapy and radiotherapy. more than 50% of drugs against cancer were isolated from natural sources, such as catharanthus roseus and epipodophyllotoxin, isolated from podophyllum. the biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. the erythroxylum suberosum is a common plant in the brazi ...201727007356
efficient regeneration and improved sonication-assisted agrobacterium transformation (saat) method for catharanthus roseus.catharanthus roseus is an important medicinal plant known for its pharmacological qualities such as antimicrobial, anticancerous, antifeedant, antisterility, antidiabetic activities. more than 130 bioactive compounds like vinblastine, vindoline and vincristine have been synthesized in this plant. extensive studies have been carried out for optimization regeneration and transformation protocols. most of the protocol described are laborious and time-consuming. due to sophisticated protocol of rege ...201728401464
top-down metabolomic approaches for nitrogen-containing metabolites.streamlining the processes that reveal heteroatom-containing metabolites and their biosynthetic genes is essential in integrated metabolomics studies. these metabolites are especially targeted for their potential pharmaceutical activities. by using a fourier-transform ion cyclotron resonance-mass spectrometry (fticr-ms) instrument, we provide top-down targeted metabolomic analyses using ultrahigh-resolution liquid chromatography-mass spectrometry (lc-ms), high-resolution matrix-assisted laser de ...201728225596
the mirnaome of catharanthus roseus: identification, expression analysis, and potential roles of micrornas in regulation of terpenoid indole alkaloid biosynthesis.micrornas (mirnas) regulate numerous crucial biological processes in plants. however, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (tias). using small rna-sequencing, we identified 181 conserved and 173 novel mirnas (cro-mirnas) in c. roseus seedlings. genome-wide expression analysis revealed that a set of cro-mirnas are ...201728223695
experimental evidence and in silico identification of tryptophan decarboxylase in citrus genus.plant tryptophan decarboxylase (tdc) converts tryptophan into tryptamine, precursor of indolealkylamine alkaloids. the recent finding of tryptamine metabolites in citrus plants leads to hypothesize the existence of tdc activity in this genus. here, we report for the first time that, in citrus x limon seedlings, deuterium labeled tryptophan is decarboxylated into tryptamine, from which successively deuterated n,n,n-trimethyltryptamine is formed. these results give an evidence of the occurrence of ...201728208655
folivory elicits a strong defense reaction in catharanthus roseus: metabolomic and transcriptomic analyses reveal distinct local and systemic responses.plants deploy distinct secondary metabolisms to cope with environment pressure and to face bio-aggressors notably through the production of biologically active alkaloids. this metabolism-type is particularly elaborated in catharanthus roseus that synthesizes more than a hundred different monoterpene indole alkaloids (mias). while the characterization of their biosynthetic pathway now reaches completion, still little is known about the role of mias during biotic attacks. as a consequence, we deve ...201728094274
an npf transporter exports a central monoterpene indole alkaloid intermediate from the vacuole.plants sequester intermediates of metabolic pathways into different cellular compartments, but the mechanisms by which these molecules are transported remain poorly understood. monoterpene indole alkaloids, a class of specialized metabolites that includes the anticancer agent vincristine, antimalarial quinine and neurotoxin strychnine, are synthesized in several different cellular locations. however, the transporters that control the movement of these biosynthetic intermediates within cellular c ...201728085153
ethnopharmacological survey of medicinal plants used by patients with psoriasis in the west bank of palestine.psoriasis is a frequent skin inflammatory disorder that inflicts millions of patients around the globe. to meet their healthcare needs, patients with psoriasis often seek treatment outside the allopathic paradigm. use of medicinal plants has emerged as one of the most common and preferred modalities of complementary and alternative medicine (cam). the aim of this study was to investigate the use of medicinal plants by patients with psoriasis in the west bank of palestine.201728049474
a differentially regulated ap2/erf transcription factor gene cluster acts downstream of a map kinase cascade to modulate terpenoid indole alkaloid biosynthesis in catharanthus roseus.catharanthus roseus produces bioactive terpenoid indole alkaloids (tias), including the chemotherapeutics, vincristine and vinblastine. transcriptional regulation of tia biosynthesis is not fully understood. the jasmonic acid (ja)-responsive ap2/erf transcription factor (tf), orca3, and its regulator, crmyc2, play key roles in tia biosynthesis. orca3 forms a physical cluster with two uncharacterized ap2/erfs, orca4 and 5. here, we report that (1) the orca gene cluster is differentially regulated ...201727801944
transcription factors regulating uspa genes in catharanthus roseus.rna-seq of the catharanthus roseus sra database was done in order to detect putative universal stress proteins (usps) and their possible controlling factors. previous analysis indicated the existence and characterization of uspa-like genes. in silico analysis of rna-seq database in several plant tissues revealed the possible functions and regulations of some uspa-like transcripts whose transcription factors (tfs) that might drive their expression were detected. blast indicated the existence of t ...201727890577
biosynthesis and regulation of terpenoid indole alkaloids in catharanthus roseus.catharanthus roseus produces a wide range of terpenoid indole alkaloids (tia). many of them, such as vinblastine and vincristine, have significant bioactivity. they are valuable chemotherapy drugs used in combination with other drugs to treat lymphoma and leukemia. the tia biosynthetic pathway has been investigated for many years, for scientific interest and for their potential in manufacturing applications, to fulfill the market demand. in this review, the progress and perspective of c. roseus ...201726009689
manipulation of ges and erg20 for geraniol overproduction in saccharomyces cerevisiae.manipulation of monoterpene synthases to maximize flux towards targeted products from gpp (geranyl diphosphate) is the main challenge for heterologous monoterpene overproduction, in addition to cell toxicity from compounds themselves. in our study, by manipulation of the key enzymes geraniol synthase (ges) and farnesyl diphosphate synthase (erg20), geraniol (a valuable acyclic monoterpene alcohol) overproduction was achieved in saccharomyces cerevisiae with truncated 3-hydroxy-3-methylglutaryl-c ...201728359705
importance of producing economic compounds to combat cancer.the manuscript published by microb biotechnol, volume 10, highlights the relevance of the fungus nigrospora sphaerica, an endophyte isolated from catharanthus roseus, as an alternative source to obtain vinblastine, a compound used in chemotherapy schemes to treat several types of cancer. authors showed that purification of vinblastine from extracts of the fungus has higher activity and yield in comparison with that obtained from the plant catharanthus roseus. this work represents a biotechnologi ...201728127869
virus-induced gene silencing in rauwolfia species.elucidation of the monoterpene indole alkaloid biosynthesis has recently progressed in apocynaceae through the concomitant development of transcriptomic analyses and reverse genetic approaches performed by virus-induced gene silencing (vigs). while most of these tools have been primarily adapted for the madagascar periwinkle (catharanthus roseus), the vigs procedure has scarcely been used on other apocynaceae species. for instance, rauwolfia sp. constitutes a unique source of specific and valuab ...201728120101
effect of pseudomonas fluorescens rb4 and bacillus subtilis 189 on the phytoremediation potential of catharanthus roseus (l.) in cu and pb-contaminated soils.the remediation of heavy metal-contaminated soils has become a critical issue due to toxic effects of these metals on living organisms. the current research was conducted to study the effect of pseudomonas fluorescens rb4 and bacillus subtilis 189 on the growth and phytoremediation potential of catharanthus roseus in cu- and pb-contaminated soils. the bacterial strains exhibited significantly higher level of water-extractable pb and cu in pb, cu, and cu+pb-contaminated. the p. fluorescens rb4 in ...201727819493
still stable after 11 years: a catharanthus roseus hairy root line maintains inducible expression of anthranilate synthase.hairy root cultures generated using agrobacterium rhizogenes are an extensively investigated system for the overproduction of various secondary metabolite based pharmaceuticals and chemicals. this study demonstrated a transgenic catharanthus roseus hairy root line carrying a feedback-insensitive anthranilate synthase (as) maintained chemical and genetic stability for 11 years. the as gene was originally inserted in the hairy root genome under the control of a glucocorticoid inducible promoter. a ...201727813337
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