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Pesquisa : D08.811.520.232.400.700 [Categoria DeCS]
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[PMID]:29360842
[Au] Autor:Liu F; Yang Y; Gao J; Ma C; Bi Y
[Ad] Endereço:College of Life Science, Shandong Normal University, Jinan, China.
[Ti] Título:A comparative transcriptome analysis of a wild purple potato and its red mutant provides insight into the mechanism of anthocyanin transformation.
[So] Source:PLoS One;13(1):e0191406, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this study, a red mutant was obtained through in vitro regeneration of a wild purple potato. High-performance liquid chromatography and Mass spectrometry analysis revealed that pelargonidin-3-O-glucoside and petunidin-3-O-glucoside were main anthocyanins in the mutant and wild type tubers, respectively. In order to thoroughly understand the mechanism of anthocyanin transformation in two materials, a comparative transcriptome analysis of the mutant and wild type was carried out through high-throughput RNA sequencing, and 295 differentially expressed genes (DEGs) were obtained. Real-time qRT-PCR validation of DEGs was consistent with the transcriptome date. The DEGs mainly influenced biological and metabolic pathways, including phenylpropanoid biosynthesis and translation, and biosynthesis of flavone and flavonol. In anthocyanin biosynthetic pathway, the analysis of structural genes expressions showed that three genes, one encoding phenylalanine ammonia-lyase, one encoding 4-coumarate-CoA ligase and one encoding flavonoid 3',5'-hydroxylasem were significantly down-regulated in the mutant; one gene encoding phenylalanine ammonia-lyase was significantly up-regulated. Moreover, the transcription factors, such as bZIP family, MYB family, LOB family, MADS family, zf-HD family and C2H2 family, were significantly regulated in anthocyanin transformation. Response proteins of hormone, such as gibberellin, abscisic acid and brassinosteroid, were also significantly regulated in anthocyanin transformation. The information contributes to discovering the candidate genes in anthocyanin transformation, which can serve as a comprehensive resource for molecular mechanism research of anthocyanin transformation in potatoes.
[Mh] Termos MeSH primário: Antocianinas/biossíntese
Antocianinas/genética
Solanum tuberosum/genética
Solanum tuberosum/metabolismo
[Mh] Termos MeSH secundário: Vias Biossintéticas/genética
Coenzima A Ligases/genética
Sistema Enzimático do Citocromo P-450/genética
Perfilação da Expressão Gênica
Regulação da Expressão Gênica de Plantas
Genes de Plantas
Glucosídeos/biossíntese
Glucosídeos/genética
Sequenciamento de Nucleotídeos em Larga Escala
Mutação
Fenilalanina Amônia-Liase/genética
Pigmentação/genética
Reguladores de Crescimento de Planta/genética
Proteínas de Plantas/genética
Tubérculos/genética
Tubérculos/metabolismo
RNA de Plantas/genética
Fatores de Transcrição/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anthocyanins); 0 (Glucosides); 0 (Plant Growth Regulators); 0 (Plant Proteins); 0 (RNA, Plant); 0 (Transcription Factors); 6988-81-4 (petunidin-3-glucoside); 8H1WZY9R6P (pelargonidin-3-glucoside); 9035-51-2 (Cytochrome P-450 Enzyme System); EC 1.14.- (flavonoid 3',5'-hydroxylase); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase); EC 6.2.1.- (Coenzyme A Ligases); EC 6.2.1.12 (4-coumarate-CoA ligase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191406


  2 / 967 MEDLINE  
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[PMID]:29191011
[Au] Autor:Zhang Z; Wang H; Wang K; Jiang L; Wang D
[Ti] Título:Use of Lentinan To Control Sharp Eyespot of Wheat, and the Mechanism Involved.
[So] Source:J Agric Food Chem;65(50):10891-10898, 2017 Dec 20.
[Is] ISSN:1520-5118
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Lentinan (LNT), a complex polysaccharide with a ß-(1→3)-linked backbone of d-glucose residues, has been reported to inhibit plant diseases. Our objective was to explore the efficacy and action mechanism of LNT used as a seed dressing to control sharp eyespot of wheat. Seed dressing promoted wheat growth. At control germination rates of 50%, 8 g of LNT/100 kg of seeds of the Jimai 22, Shannong 23, and Luyuan 502 cultivars significantly increased seed germination to 54%, 52%, and 51%, respectively. Seven days after emergence, the heights and root activity of wheat treated with LNT were significantly greater than those of controls. These effects were dose-dependent. At this time, the plant heights of Jimai 22, Shannong 23, and Luyuan 502 cultivars were 9.52, 8.52, and 10.52 cm, respectively, significantly higher than that of the controls. LNT prevented the development of wheat sharp eyespot. In the highly susceptible Jimai 22 cultivar, sharp eyespot development was reduced by 33.7%, 31.9%, and 30.4% at 7, 14, and 21 days after germination. LNT somewhat increased phenylalanine ammonia-lyase, peroxidase, and superoxide dismutase activity; reduced the malondialdehyde content; increased chlorophyll a and b levels; and enhanced the root vigor of wheat. These effects peaked 7 days after germination. LNT increased transcription of the genes encoding alternative oxidase (AOX) and ß-1,3-glucanase (GLU), the salicylic acid signaling pathway-related gene NbPR1a, and the sharp eyespot resistance-related gene RS33. A significant dose-effect relationship was evident in terms of AOX transcription; we thus speculate that AOX may be the target gene.
[Mh] Termos MeSH primário: Fungicidas Industriais/farmacologia
Lentinano/farmacologia
Doenças das Plantas/prevenção & controle
Extratos Vegetais/farmacologia
Rhizoctonia/efeitos dos fármacos
Cogumelos Shiitake/química
Triticum/microbiologia
[Mh] Termos MeSH secundário: Clorofila/metabolismo
Fungicidas Industriais/química
Germinação/efeitos dos fármacos
Lentinano/química
Malondialdeído/metabolismo
Fenilalanina Amônia-Liase/genética
Fenilalanina Amônia-Liase/metabolismo
Doenças das Plantas/microbiologia
Extratos Vegetais/química
Proteínas de Plantas/genética
Proteínas de Plantas/metabolismo
Rhizoctonia/fisiologia
Sementes/crescimento & desenvolvimento
Sementes/microbiologia
Superóxido Dismutase/genética
Superóxido Dismutase/metabolismo
Triticum/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fungicides, Industrial); 0 (Plant Extracts); 0 (Plant Proteins); 1406-65-1 (Chlorophyll); 37339-90-5 (Lentinan); 4Y8F71G49Q (Malondialdehyde); EC 1.15.1.1 (Superoxide Dismutase); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase); YF5Q9EJC8Y (chlorophyll a)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180110
[Lr] Data última revisão:
180110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jafc.7b04665


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[PMID]:28451820
[Au] Autor:Fantino E; Segretin ME; Santin F; Mirkin FG; Ulloa RM
[Ad] Endereço:Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor Torres" (INGEBI-CONICET) Vuelta de Obligado 2490, 2do piso, Ciudad Autónoma de Buenos Aires, Argentina.
[Ti] Título:Analysis of the potato calcium-dependent protein kinase family and characterization of StCDPK7, a member induced upon infection with Phytophthora infestans.
[So] Source:Plant Cell Rep;36(7):1137-1157, 2017 Jul.
[Is] ISSN:1432-203X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:KEY MESSAGE: We describe the potato CDPK family and place StCDPK7 as a player in potato response to Phytophthora infestans infection, identifying phenylalanine ammonia lyase as its specific phosphorylation target in vitro. Calcium-dependent protein kinases (CDPKs) decode calcium (Ca ) signals and activate different signaling pathways involved in hormone signaling, plant growth, development, and both abiotic and biotic stress responses. In this study, we describe the potato CDPK/CRK multigene family; bioinformatic analysis allowed us to identify 20 new CDPK isoforms, three CDPK-related kinases (CRKs), and a CDPK-like kinase. Phylogenetic analysis indicated that 26 StCDPKs can be classified into four groups, whose members are predicted to undergo different acylation patterns and exhibited diverse expression levels in different tissues and in response to various stimuli. With the aim of characterizing those members that are particularly involved in plant-pathogen interaction, we focused on StCDPK7. Tissue expression profile revealed that StCDPK7 transcript levels are high in swollen stolons, roots, and mini tubers. Moreover, its expression is induced upon Phytophthora infestans infection in systemic leaves. Transient expression assays showed that StCDPK7 displays a cytosolic/nuclear localization in spite of having a predicted chloroplast transit peptide. The recombinant protein, StCDPK7:6xHis, is an active Ca -dependent protein kinase that can phosphorylate phenylalanine ammonia lyase, an enzyme involved in plant defense response. The analysis of the potato CDPK family provides the first step towards the identification of CDPK isoforms involved in biotic stress. StCDPK7 emerges as a relevant player that could be manipulated to deploy disease resistance in potato crops.
[Mh] Termos MeSH primário: Phytophthora infestans/fisiologia
Proteínas de Plantas/genética
Proteínas Quinases/genética
Proteínas Quinases/metabolismo
Solanum tuberosum/genética
Solanum tuberosum/parasitologia
[Mh] Termos MeSH secundário: Núcleo Celular/enzimologia
Núcleo Celular/metabolismo
Citosol/enzimologia
Citosol/metabolismo
Resistência à Doença/genética
Fenilalanina Amônia-Liase/genética
Fenilalanina Amônia-Liase/metabolismo
Doenças das Plantas/genética
Doenças das Plantas/microbiologia
Proteínas de Plantas/metabolismo
Solanum tuberosum/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Plant Proteins); EC 2.7.- (Protein Kinases); EC 2.7.1.- (calcium-dependent protein kinase); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171212
[Lr] Data última revisão:
171212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1007/s00299-017-2144-x


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[PMID]:28520731
[Au] Autor:Durrer KE; Allen MS; Hunt von Herbing I
[Ad] Endereço:Department of Biological Sciences, University of North Texas, Denton, Texas, United States of America.
[Ti] Título:Genetically engineered probiotic for the treatment of phenylketonuria (PKU); assessment of a novel treatment in vitro and in the PAHenu2 mouse model of PKU.
[So] Source:PLoS One;12(5):e0176286, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phenylketonuria (PKU) is a genetic disease characterized by the inability to convert dietary phenylalanine to tyrosine by phenylalanine hydroxylase. Given the importance of gut microbes in digestion, a genetically engineered microbe could potentially degrade some ingested phenylalanine from the diet prior to absorption. To test this, a phenylalanine lyase gene from Anabaena variabilis (AvPAL) was codon-optimized and cloned into a shuttle vector for expression in Lactobacillus reuteri 100-23C (pHENOMMenal). Functional expression of AvPAL was determined in vitro, and subsequently tested in vivo in homozygous PAHenu2 (PKU model) mice. Initial trials of two PAHenu2 homozygous (PKU) mice defined conditions for freeze-drying and delivery of bacteria. Animals showed reduced blood phe within three to four days of treatment with pHENOMMenal probiotic, and blood phe concentrations remained significantly reduced (P < 0.0005) compared to untreated controls during the course of experiments. Although pHENOMMenal probiotic could be cultured from fecal samples at four months post treatment, it could no longer be cultivated from feces at eight months post treatment, indicating eventual loss of the microbe from the gut. Preliminary screens during experimentation found no immune response to AvPAL. Collectively these studies provide data for the use of a genetically engineered probiotic as a potential treatment for PKU.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Fenilalanina Amônia-Liase/genética
Fenilcetonúrias/terapia
Probióticos/uso terapêutico
[Mh] Termos MeSH secundário: Anabaena variabilis/genética
Animais
Proteínas de Bactérias/metabolismo
Intestinos/metabolismo
Intestinos/microbiologia
Lactobacillus reuteri/genética
Camundongos
Camundongos Endogâmicos C57BL
Fenilalanina/sangue
Fenilalanina/metabolismo
Fenilalanina Amônia-Liase/metabolismo
Probióticos/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 47E5O17Y3R (Phenylalanine); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170519
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176286


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[PMID]:28433594
[Au] Autor:Zafari S; Sharifi M; Mur LAJ; Chashmi NA
[Ad] Endereço:Department of Plant Biology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
[Ti] Título:Favouring NO over H O production will increase Pb tolerance in Prosopis farcta via altered primary metabolism.
[So] Source:Ecotoxicol Environ Saf;142:293-302, 2017 Aug.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Reactive oxygen species (ROS) and nitric oxide (NO) are known in triggering defense functions to detoxify heavy metal stresses. To investigate the relevance of ROS production, Pb treatment (400µM) alone and in combination with 400µM sodium ascorbate (Asc: as H O scavenger) were given to hydroponically grown Prosopis farcta seedlings over a time course of 72h. Data presented here indicate that, the low extent of H O due to scavenging by ascorbate, together with high level of NO improved Pb+Asc- treated Prosopis growth. Following the evoked potential of both the signals, significant increases in phenolic acids; caffeic, ferulic and salicylic acid were observed with Pb treatment; which are consistent with observed increase in lignin content and consequently with growth inhibition. In contrast, Pb+Asc treatment induced more flavonoids (quercetin, kaempferol, luteolin), diminished phenolic acids contents and also lignin. Elicited expression rate of phenylalanine ammonia-lyase gene (PAL) and also its enzymatic activity verified the induced phenylpropanoid metabolism by Pb and Pb+Asc treatments. In comparison with Pb stress, Asc+Pb application induced the high expression of arginine decarboxylase gene (ADC), in polyamines biosynthesis pathway, and conducted the N flow towards polyamines and γ-amino butyric acid (GABA). Examining the impact on enzyme activities, catalase, and guaiacol peroxidase; Pb+Asc reduced activity but this increased ascorbate peroxidase, and aconitase activity. Our observations are consistent with conditions favouring NO production and reduced H O can improve Pb tolerance via wide-ranging effects on a primary metabolic network.
[Mh] Termos MeSH primário: Peróxido de Hidrogênio/metabolismo
Chumbo/toxicidade
Metaboloma/efeitos dos fármacos
Óxido Nítrico/metabolismo
Prosopis/metabolismo
Poluentes do Solo/toxicidade
[Mh] Termos MeSH secundário: Ascorbato Peroxidases/metabolismo
Ácido Ascórbico/metabolismo
Ácido Ascórbico/farmacologia
Catalase/metabolismo
Flavonoides/metabolismo
Hidroxibenzoatos/metabolismo
Peroxidase/metabolismo
Fenilalanina Amônia-Liase/metabolismo
Prosopis/efeitos dos fármacos
Espécies Reativas de Oxigênio/metabolismo
Plântulas/efeitos dos fármacos
Plântulas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Flavonoids); 0 (Hydroxybenzoates); 0 (Reactive Oxygen Species); 0 (Soil Pollutants); 29656-58-4 (phenolic acid); 2P299V784P (Lead); 31C4KY9ESH (Nitric Oxide); BBX060AN9V (Hydrogen Peroxide); EC 1.11.1.- (guaiacol peroxidase); EC 1.11.1.11 (Ascorbate Peroxidases); EC 1.11.1.6 (Catalase); EC 1.11.1.7 (Peroxidase); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170424
[St] Status:MEDLINE


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[PMID]:28363172
[Au] Autor:Jiang S; Weng B; Liu T; Su Y; Liu J; Lu H; Yan C
[Ad] Endereço:Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystems, Xiamen University, Xiamen 361005, China.
[Ti] Título:Response of phenolic metabolism to cadmium and phenanthrene and its influence on pollutant translocations in the mangrove plant Aegiceras corniculatum (L.) Blanco (Ac).
[So] Source:Ecotoxicol Environ Saf;141:290-297, 2017 Jul.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Polyphenolic compounds are abundant in mangrove plants, playing a pivotal role in the detoxification of pollutants extruded from surrounding environments into plant tissues. The present study aimed to examine the variations of phenolic compounds, namely total polyphenolics, soluble tannins, condensed tannins and lignin, in the mangrove plant Aegiceras corniculatum (L.) due to the presence of exogenous cadmium and phenanthrene and to explore the influence of phenolic metabolism on biological translocation of these pollutants from roots to leaves. After a 6-week exposure to cadmium and phenanthrene, significant accumulations of both pollutants were observed. All determined phenolic compounds in both leaves and roots at high dosage levels were enhanced compared to the uncontaminated plant. Elevations of polyphenols in both treatments are possibly a result of stimulation in the activity of phenylalanine ammonia-lyase (PAL) and the enrichment of soluble sugar. Additionally, a significantly positive dosage relationship between polyphenolic metabolism intensity and phenanthrene contamination levels was found, while the trend observed in cadmium treatment was weak since cadmium at high levels inhibited phenolic production. The enrichment of polyphenols led to a decline in the biological translocation of these pollutants from roots to leaves. The immobilization of pollutants in the plant roots is possibly linked to the adsorption potential of polyphenols. These results will improve the understanding of the tolerance of mangrove plants to exogenous pollutants and will guide the selection of plants in phytoremediation because of the variability of polyphenol concentrations among species.
[Mh] Termos MeSH primário: Cádmio/toxicidade
Poluentes Ambientais/toxicidade
Myrsinaceae/efeitos dos fármacos
Fenantrenos/toxicidade
Polifenóis/metabolismo
[Mh] Termos MeSH secundário: Biodegradação Ambiental
Transporte Biológico
Cádmio/metabolismo
China
Poluentes Ambientais/metabolismo
Myrsinaceae/crescimento & desenvolvimento
Myrsinaceae/metabolismo
Fenantrenos/metabolismo
Fenilalanina Amônia-Liase/metabolismo
Folhas de Planta/efeitos dos fármacos
Folhas de Planta/metabolismo
Raízes de Plantas/efeitos dos fármacos
Raízes de Plantas/metabolismo
Zonas Úmidas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Environmental Pollutants); 0 (Phenanthrenes); 0 (Polyphenols); 00BH33GNGH (Cadmium); 448J8E5BST (phenanthrene); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE


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[PMID]:28285020
[Au] Autor:Cunha AG; Brito ES; Moura CF; Ribeiro PR; Miranda MR
[Ad] Endereço:Federal University of Ceará. Dept. of Biochemistry and Molecular Biology, Campus Pici,Av. Mister Hull 2297 Bl. 907, Fortaleza, CE, CEP 60440-554, Brazil.
[Ti] Título:UPLC-qTOF-MS/MS-based phenolic profile and their biosynthetic enzyme activity used to discriminate between cashew apple (Anacardium occidentale L.) maturation stages.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1051:24-32, 2017 Apr 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Cashew immature and ripe peduncles (Anacardium occidentale L.) from orange- and red-colored clones CCP 76 and BRS 189, respectively, were prepared as juice or fibrous fraction and submitted to UPLC-MS analyses, while the soluble fraction was also submitted to enzymatic evaluation. Cinnamoyl glucoside was present in ripe juice samples from both cashew clones, while monogalloyl diglucoside and digalloyl glucoside were present in immature juice samples from both cashew clones. Four compounds were found at immature fiber of both clones, anacardic acids (1, 2, 3) and GA . The phenolic biosynthetic pathway was evaluated in juice samples and phenylalanine ammonia-lyase activity decreased significantly during the development, although it was much higher in ripe CCP 76. UDP-glycosyltransferases activity differed between clones, however its product cinnamoyl glucoside was a possible chemical marker of ripe juice samples from both clones. Flavonol synthase showed the highest specific activity in both cashew clones and its product, flavonols were identified in cashew apple at immature and ripe stages.
[Mh] Termos MeSH primário: Ácidos Anacárdicos/análise
Anacardium/enzimologia
Anacardium/crescimento & desenvolvimento
Frutas/enzimologia
Frutas/crescimento & desenvolvimento
Glucosídeos/análise
Fenóis/análise
[Mh] Termos MeSH secundário: Ácidos Anacárdicos/metabolismo
Anacardium/química
Anacardium/metabolismo
Vias Biossintéticas
Cromatografia Líquida de Alta Pressão
Frutas/química
Frutas/metabolismo
Glucosídeos/metabolismo
Glucuronosiltransferase/metabolismo
Oxirredutases/metabolismo
Fenóis/metabolismo
Fenilalanina Amônia-Liase/metabolismo
Proteínas de Plantas/metabolismo
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anacardic Acids); 0 (Glucosides); 0 (Phenols); 0 (Plant Proteins); EC 1.- (Oxidoreductases); EC 1.3.- (flavonol synthase); EC 2.4.1.17 (Glucuronosyltransferase); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170601
[Lr] Data última revisão:
170601
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170313
[St] Status:MEDLINE


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[PMID]:28282402
[Au] Autor:Bell SM; Wendt DJ; Zhang Y; Taylor TW; Long S; Tsuruda L; Zhao B; Laipis P; Fitzpatrick PA
[Ad] Endereço:BioMarin Pharmaceutical, Novato, California, United States of America.
[Ti] Título:Formulation and PEGylation optimization of the therapeutic PEGylated phenylalanine ammonia lyase for the treatment of phenylketonuria.
[So] Source:PLoS One;12(3):e0173269, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phenylketonuria (PKU) is a genetic metabolic disease in which the decrease or loss of phenylalanine hydroxylase (PAH) activity results in elevated, neurotoxic levels of phenylalanine (Phe). Due to many obstacles, PAH enzyme replacement therapy is not currently an option. Treatment of PKU with an alternative enzyme, phenylalanine ammonia lyase (PAL), was first proposed in the 1970s. However, issues regarding immunogenicity, enzyme production and mode of delivery needed to be overcome. Through the evaluation of PAL enzymes from multiple species, three potential PAL enzymes from yeast and cyanobacteria were chosen for evaluation of their therapeutic potential. The addition of polyethylene glycol (PEG, MW = 20,000), at a particular ratio to modify the protein surface, attenuated immunogenicity in an animal model of PKU. All three PEGylated PAL candidates showed efficacy in a mouse model of PKU (BTBR Pahenu2) upon subcutaneous injection. However, only PEGylated Anabaena variabilis (Av) PAL-treated mice demonstrated sustained low Phe levels with weekly injection and was the only PAL evaluated that maintained full enzymatic activity upon PEGylation. A PEGylated recombinant double mutant version of AvPAL (Cys503Ser/Cys565Ser), rAvPAL-PEG, was selected for drug development based on its positive pharmacodynamic profile and favorable expression titers. PEGylation was shown to be critical for rAvPAL-PEG efficacy as under PEGylated rAvPAL had a lower pharmacodynamic effect. rAvPAL and rAvPAL-PEG had poor stability at 4°C. L-Phe and trans-cinnamate were identified as activity stabilizing excipients. rAvPAL-PEG is currently in Phase 3 clinical trials to assess efficacy in PKU patients.
[Mh] Termos MeSH primário: Fenilalanina Amônia-Liase/uso terapêutico
Fenilcetonúrias/tratamento farmacológico
Polietilenoglicóis/química
[Mh] Termos MeSH secundário: Anabaena/enzimologia
Animais
Anticorpos/sangue
Modelos Animais de Doenças
Composição de Medicamentos
Terapia de Reposição de Enzimas
Ensaio de Imunoadsorção Enzimática
Camundongos
Nostoc/enzimologia
Petroselinum/enzimologia
Fenilalanina Amônia-Liase/química
Fenilalanina Amônia-Liase/imunologia
Fenilalanina Amônia-Liase/isolamento & purificação
Fenilcetonúrias/patologia
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/química
Proteínas Recombinantes/isolamento & purificação
Proteínas Recombinantes/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Recombinant Proteins); 30IQX730WE (Polyethylene Glycols); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0173269


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[PMID]:28274102
[Au] Autor:Kim EJ; Cha MN; Kim BG; Ahn JH
[Ad] Endereço:Department of Integrative Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul 05029, Republic of Korea.
[Ti] Título:Production of Curcuminoids in .
[So] Source:J Microbiol Biotechnol;27(5):975-982, 2017 May 28.
[Is] ISSN:1738-8872
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Curcumin, a hydrophobic polyphenol derived from the rhizome of the herb , possesses diverse pharmacological properties, including anti-inflammatory, antioxidant, antiproliferative, and antiangiogenic activities. Two curcuminoids (dicinnamoylmethane and bisdemethoxycurcumin) were synthesized from glucose in . (phenylalanine ammonia lyase) or (tyrosine ammonia lyase), along with ( -coumaroyl-CoA ligase) and (curcumin synthase) genes, were introduced into , and each strain produced dicinnamoylmethane or bisdemethoxycurcumin, respectively. In order to increase the production of curcuminoids in , the shikimic acid biosynthesis pathway, which increases the substrates for curcuminoid biosynthesis, was engineered. Using the engineered strains, the production of bisdemethoxycurcumin increased from 0.32 to 4.63 mg/l, and that of dicinnamoylmethane from 1.24 to 6.95 mg/l.
[Mh] Termos MeSH primário: Curcumina/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Engenharia Metabólica/métodos
[Mh] Termos MeSH secundário: Amônia-Liases/genética
Amônia-Liases/metabolismo
Arabidopsis/genética
Vias Biossintéticas/genética
Meios de Cultura
Curcumina/análogos & derivados
Curcumina/química
Regulação Bacteriana da Expressão Gênica
Glucose/metabolismo
Microbiologia Industrial
Ligases/genética
Ligases/metabolismo
Fenilalanina Amônia-Liase/genética
Fenilalanina Amônia-Liase/metabolismo
Ácido Chiquímico/metabolismo
Tirosina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Culture Media); 0 (dicinnamoylmethane); 29MS2WI2NU (Shikimic Acid); 2EFO1BP34R (bis(4-hydroxycinnamoyl)methane); 42HK56048U (Tyrosine); EC 4.3.1.- (Ammonia-Lyases); EC 4.3.1.- (L-tyrosine ammonia-lyase); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase); EC 6.- (Ligases); EC 6.- (curcuminoid synthase, Curcuma longa); IT942ZTH98 (Curcumin); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.4014/jmb.1701.01030


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[PMID]:28254020
[Au] Autor:Guardado-Félix D; Serna-Saldivar SO; Cuevas-Rodríguez EO; Jacobo-Velázquez DA; Gutiérrez-Uribe JA
[Ad] Endereço:Programa Regional de Posgrado en Biotecnología, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Sinaloa, FCQB-UAS, AP 1354, CP 80000 Culiacán, Sinaloa, Mexico.
[Ti] Título:Effect of sodium selenite on isoflavonoid contents and antioxidant capacity of chickpea (Cicer arietinum L.) sprouts.
[So] Source:Food Chem;226:69-74, 2017 Jul 01.
[Is] ISSN:0308-8146
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Isoflavonoid compositions, phenylalanine ammonia lyase (PAL) activity and antioxidant capacity were evaluated in chickpea (Cicer arietinum L.) sprouts germinated after soaking with different sodium selenite (Na SeO ) concentrations (0, 1 and 2mg/100g seeds). Chickpea seeds were germinated during four days at 24°C and the isoflavonoid profiles and concentrations evaluated by HPLC-UV daily during four days of germination. Eleven isoflavones and two pterocarpan phytoalexins forms were identified in sprouts, being malonylated formononetin glycoside, formononetin, isoformononetin glycoside and malonylated biochanin A glycoside the major compounds. Compared to untreated sprouts, total isoflavonoid, PAL activity and antioxidant capacity showed a remarkable increase of 83%, 56%, and 33%, respectively in chickpea sprouts that were treated with a high sodium selenite content (2mg/100g seeds). Results suggest that Se-enriched chickpea sprouts could represent a good source of dietary Se and as an upgraded source of isoflavonoids.
[Mh] Termos MeSH primário: Antioxidantes
Cicer/efeitos dos fármacos
Isoflavonas
Fenilalanina Amônia-Liase/genética
Selenito de Sódio/farmacologia
[Mh] Termos MeSH secundário: Cicer/química
Cicer/enzimologia
Regulação da Expressão Gênica de Plantas
Plântulas/química
Plântulas/efeitos dos fármacos
Plântulas/enzimologia
Sesquiterpenos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (Isoflavones); 0 (Sesquiterpenes); 37297-20-4 (phytoalexins); EC 4.3.1.24 (Phenylalanine Ammonia-Lyase); HIW548RQ3W (Sodium Selenite)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170304
[St] Status:MEDLINE



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