Base de dados : MEDLINE
Pesquisa : D08.811.399 [Categoria DeCS]
Referências encontradas : 3675 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 368 ir para página                         

  1 / 3675 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28759016
[Au] Autor:Mori T; Iwabuchi T; Hoshino S; Wang H; Matsuda Y; Abe I
[Ad] Endereço:Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
[Ti] Título:Molecular basis for the unusual ring reconstruction in fungal meroterpenoid biogenesis.
[So] Source:Nat Chem Biol;13(10):1066-1073, 2017 Oct.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Trt14 from Aspergillus terreus is involved in unusual skeletal reconstruction during the biosynthesis of the fungal meroterpenoid terretonin. Detailed in vitro characterization revealed that this novel multifunctional enzyme catalyzes not only the D-ring expansion via intramolecular methoxy rearrangement, but also the hydrolysis of the expanded D-ring. The X-ray crystal structures of Trt14, in complex with substrate or product, and two Trt14 homologs, AusH and PrhC from Aspergillus nidulans and Penicillium brasilianum, respectively, indicated similar overall structures to those of the NTF2-like superfamily of enzymes, despite lacking sequence and functional similarities. Moreover, we gained structural insight into the mechanism of the Trt14-catalyzed ring reconstruction from the in-crystal enzyme reaction and site-directed mutagenesis to show that this reaction involves sequential ester bond cleavage and formation. Structural comparison of Trt14 and its homologs suggests that the enzymes in this new superfamily employ similar acid-base chemistry to diversify the molecular architecture of fungal meroterpenoids.
[Mh] Termos MeSH primário: Aspergillus/metabolismo
Isomerases/metabolismo
Terpenos/química
Terpenos/metabolismo
[Mh] Termos MeSH secundário: Aspergillus/enzimologia
Cristalografia por Raios X
Isomerases/química
Isomerases/genética
Modelos Moleculares
Estrutura Molecular
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Terpenes); EC 5.- (Isomerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170801
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2443


  2 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28513176
[Au] Autor:Ranjan N; Story S; Fulcrand G; Leng F; Ahmad M; King A; Sur S; Wang W; Tse-Dinh YC; Arya DP
[Ad] Endereço:Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University , Clemson, South Carolina 29634, United States.
[Ti] Título:Selective Inhibition of Escherichia coli RNA and DNA Topoisomerase I by Hoechst 33258 Derived Mono- and Bisbenzimidazoles.
[So] Source:J Med Chem;60(12):4904-4922, 2017 Jun 22.
[Is] ISSN:1520-4804
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A series of Hoechst 33258 based mono- and bisbenzimidazoles have been synthesized and their Escherichia coli DNA topoisomerase I inhibition, binding to B-DNA duplex, and antibacterial activity has been evaluated. Bisbenzimidazoles with alkynyl side chains display excellent E. coli DNA topoisomerase I inhibition properties with IC values <5.0 µM. Several bisbenzimidazoles (3, 6, 7, 8) also inhibit RNA topoisomerase activity of E. coli DNA topoisomerase I. Bisbenzimidazoles inhibit bacterial growth much better than monobenzimidazoles for Gram-positive strains. The minimum inhibitory concentration (MIC) was much lower for Gram positive bacteria (Enterococcus spp. and Staphylococcus spp., including two MRSA strains 0.3-8 µg/mL) than for the majority of Gram negative bacteria (Pseudomonas aeruginosa, 16-32 µg/mL, Klebsiella pneumoniae > 32 µg/mL). Bisbenzimidazoles showed varied stabilization of B-DNA duplex (1.2-23.4 °C), and cytotoxicity studies show similar variation dependent upon the side chain length. Modeling studies suggest critical interactions between the inhibitor side chain and amino acids of the active site of DNA topoisomerase I.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Benzimidazóis/farmacologia
Bisbenzimidazol/química
Escherichia coli/efeitos dos fármacos
Inibidores da Topoisomerase I/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Benzimidazóis/química
Linhagem Celular Tumoral
Técnicas de Química Sintética
DNA/metabolismo
Avaliação Pré-Clínica de Medicamentos/métodos
Ensaios de Seleção de Medicamentos Antitumorais/métodos
Escherichia coli/genética
Proteínas de Escherichia coli/antagonistas & inibidores
Seres Humanos
Concentração Inibidora 50
Isomerases/antagonistas & inibidores
Masculino
Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Simulação de Acoplamento Molecular
Inibidores da Topoisomerase I/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Benzimidazoles); 0 (Escherichia coli Proteins); 0 (Topoisomerase I Inhibitors); 9007-49-2 (DNA); EC 5.- (Isomerases); LHQ7J5KV9B (Bisbenzimidazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jmedchem.7b00191


  3 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28426139
[Au] Autor:Rahimi M; van der Meer JY; Geertsema EM; Poelarends GJ
[Ad] Endereço:Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
[Ti] Título:Engineering a Promiscuous Tautomerase into a More Efficient Aldolase for Self-Condensations of Linear Aliphatic Aldehydes.
[So] Source:Chembiochem;18(14):1435-1441, 2017 Jul 18.
[Is] ISSN:1439-7633
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:The enzyme 4-oxalocrotonate tautomerase (4-OT) from Pseudomonas putida mt-2 takes part in a catabolic pathway for aromatic hydrocarbons, where it catalyzes the conversion of 2hydroxyhexa-2,4-dienedioate into 2-oxohexa-3-enedioate. This tautomerase can also promiscuously catalyze carbon-carbon bond-forming reactions, including various types of aldol reactions, by using its amino-terminal proline as a key catalytic residue. Here, we used systematic mutagenesis to identify two hotspots in 4-OT (Met45 and Phe50) at which single mutations give marked improvements in aldolase activity for the self-condensation of propanal. Activity screening of a focused library in which these two hotspots were varied led to the discovery of a 4-OT variant (M45Y/F50V) with strongly enhanced aldolase activity in the self-condensation of linear aliphatic aldehydes, such as acetaldehyde, propanal, and butanal, to yield α,ß-unsaturated aldehydes. With both propanal and benzaldehyde, this double mutant, unlike the previously constructed single mutant F50A, mainly catalyzes the self-condensation of propanal rather than the cross-condensation of propanal and benzaldehyde, thus indicating that it indeed has altered substrate specificity. This variant could serve as a template to create new biocatalysts that lack dehydration activity and possess further enhanced aldolase activity, thus enabling the efficient enzymatic self-coupling of aliphatic aldehydes.
[Mh] Termos MeSH primário: Aldeídos/metabolismo
Frutose-Bifosfato Aldolase/metabolismo
Isomerases/metabolismo
Engenharia de Proteínas
Pseudomonas putida/enzimologia
[Mh] Termos MeSH secundário: Aldeídos/química
Frutose-Bifosfato Aldolase/química
Frutose-Bifosfato Aldolase/genética
Isomerases/química
Isomerases/genética
Estrutura Molecular
Pseudomonas putida/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aldehydes); EC 4.1.2.13 (Fructose-Bisphosphate Aldolase); EC 5.- (4-oxalocrotonate tautomerase); EC 5.- (Isomerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1002/cbic.201700121


  4 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28362483
[Au] Autor:Pemberton TA; Chen M; Harris GG; Chou WK; Duan L; Köksal M; Genshaft AS; Cane DE; Christianson DW
[Ad] Endereço:Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania , 231 South 34th Street, Philadelphia, Pennsylvania 19104-6323, United States.
[Ti] Título:Exploring the Influence of Domain Architecture on the Catalytic Function of Diterpene Synthases.
[So] Source:Biochemistry;56(14):2010-2023, 2017 Apr 11.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Terpenoid synthases catalyze isoprenoid cyclization reactions underlying the generation of more than 80,000 natural products. Such dramatic chemodiversity belies the fact that these enzymes generally consist of only three domain folds designated as α, ß, and γ. Catalysis by class I terpenoid synthases occurs exclusively in the α domain, which is found with α, αα, αß, and αßγ domain architectures. Here, we explore the influence of domain architecture on catalysis by taxadiene synthase from Taxus brevifolia (TbTS, αßγ), fusicoccadiene synthase from Phomopsis amygdali (PaFS, (αα) ), and ophiobolin F synthase from Aspergillus clavatus (AcOS, αα). We show that the cyclization fidelity and catalytic efficiency of the α domain of TbTS are severely compromised by deletion of the ßγ domains; however, retention of the ß domain preserves significant cyclization fidelity. In PaFS, we previously demonstrated that one α domain similarly influences catalysis by the other α domain [ Chen , M. , Chou , W. K. W. , Toyomasu , T. , Cane , D. E. , and Christianson , D. W. ( 2016 ) ACS Chem. Biol. 11 , 889 - 899 ]. Here, we show that the hexameric quaternary structure of PaFS enables cluster channeling. We also show that the α domains of PaFS and AcOS can be swapped so as to make functional chimeric αα synthases. Notably, both cyclization fidelity and catalytic efficiency are altered in all chimeric synthases. Twelve newly formed and uncharacterized C diterpene products and three C sesterterpene products are generated by these chimeras. Thus, engineered αßγ and αα terpenoid cyclases promise to generate chemodiversity in the greater family of terpenoid natural products.
[Mh] Termos MeSH primário: Alquil e Aril Transferases/química
Aspergillus/genética
Isomerases/química
Proteínas Mutantes Quiméricas/química
Saccharomycetales/genética
Taxus/genética
[Mh] Termos MeSH secundário: Alquil e Aril Transferases/genética
Alquil e Aril Transferases/metabolismo
Aspergillus/enzimologia
Ciclização
Diterpenos/metabolismo
Expressão Gênica
Isomerases/genética
Isomerases/metabolismo
Cinética
Modelos Moleculares
Proteínas Mutantes Quiméricas/genética
Proteínas Mutantes Quiméricas/metabolismo
Domínios Proteicos
Engenharia de Proteínas
Estrutura Secundária de Proteína
Saccharomycetales/enzimologia
Sesterterpenos/biossíntese
Taxus/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diterpenes); 0 (Mutant Chimeric Proteins); 0 (Sesterterpenes); 0 (fusicoccadiene); EC 2.5.- (Alkyl and Aryl Transferases); EC 2.5.1.- (ophiobolin F synthase, Aspergillus clavatus); EC 5.- (Isomerases); EC 5.- (taxa-4(5),11(12)-diene synthase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00137


  5 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28323419
[Au] Autor:Bühning M; Valleriani A; Leimkühler S
[Ad] Endereço:Institute of Biochemistry and Biology, University of Potsdam , D-14476 Potsdam, Germany.
[Ti] Título:The Role of SufS Is Restricted to Fe-S Cluster Biosynthesis in Escherichia coli.
[So] Source:Biochemistry;56(14):1987-2000, 2017 Apr 11.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Escherichia coli, two different systems that are important for the coordinate formation of Fe-S clusters have been identified, namely, the ISC and SUF systems. The ISC system is the housekeeping Fe-S machinery, which provides Fe-S clusters for numerous cellular proteins. The IscS protein of this system was additionally revealed to be the primary sulfur donor for several sulfur-containing molecules with important biological functions, among which are the molybdenum cofactor (Moco) and thiolated nucleosides in tRNA. Here, we show that deletion of central components of the ISC system in addition to IscS leads to an overall decrease in Fe-S cluster enzyme and molybdoenzyme activity in addition to a decrease in the number of Fe-S-dependent thiomodifications of tRNA, based on the fact that some proteins involved in Moco biosynthesis and tRNA thiolation are Fe-S-dependent. Complementation of the ISC deficient strains with the suf operon restored the activity of Fe-S-containing proteins, including the MoaA protein, which is involved in the conversion of 5'GTP to cyclic pyranopterin monophosphate in the fist step of Moco biosynthesis. While both systems share a high degree of similarity, we show that the function of their respective l-cysteine desulfurase IscS or SufS is specific for each cellular pathway. It is revealed that SufS cannot play the role of IscS in sulfur transfer for the formation of 2-thiouridine, 4-thiouridine, or the dithiolene group of molybdopterin, being unable to interact with TusA or ThiI. The results demonstrate that the role of the SUF system is exclusively restricted to Fe-S cluster assembly in the cell.
[Mh] Termos MeSH primário: Liases de Carbono-Enxofre/metabolismo
Escherichia coli/metabolismo
Regulação Bacteriana da Expressão Gênica
Proteínas com Ferro-Enxofre/metabolismo
Liases/metabolismo
[Mh] Termos MeSH secundário: Liases de Carbono-Enxofre/genética
Coenzimas/biossíntese
Escherichia coli/genética
Proteínas de Escherichia coli/genética
Proteínas de Escherichia coli/metabolismo
Proteínas com Ferro-Enxofre/genética
Isomerases/genética
Isomerases/metabolismo
Liases/genética
Metaloproteínas/biossíntese
Óperon
Pteridinas
RNA de Transferência/genética
RNA de Transferência/metabolismo
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Sulfurtransferases/genética
Sulfurtransferases/metabolismo
Tiouridina/análogos & derivados
Tiouridina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-thiouridine); 0 (Coenzymes); 0 (Escherichia coli Proteins); 0 (Iron-Sulfur Proteins); 0 (Metalloproteins); 0 (Pteridines); 0 (Recombinant Proteins); 0 (TusA protein, E coli); 13957-31-8 (Thiouridine); 73508-07-3 (molybdenum cofactor); 9014-25-9 (RNA, Transfer); EC 2.8.1.- (Sulfurtransferases); EC 2.8.1.- (thiI protein, E coli); EC 4.- (Lyases); EC 4.4.- (Carbon-Sulfur Lyases); EC 4.4.1.- (cysteine desulfurase); EC 4.4.1.16 (selenocysteine lyase); EC 5.- (Isomerases); EC 5.- (MoaA protein, E coli)
[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:170322
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.7b00040


  6 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28217906
[Au] Autor:Bian G; Yuan Y; Tao H; Shi X; Zhong X; Han Y; Fu S; Fang C; Deng Z; Liu T
[Ad] Endereço:Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, P. R. China.
[Ti] Título:Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6.
[So] Source:Biotechnol J;12(4), 2017 Apr.
[Is] ISSN:1860-7314
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Taxol (paclitaxel) is a diterpenoid compound with significant and extensive applications in the treatment of cancer. The production of Taxol and relevant intermediates by engineered microbes is an attractive alternative to the semichemical synthesis of Taxol. In this study, based on a previously developed platform, the authors first established taxadiene production in mutant E. coli T2 and T4 by engineering of the mevalonate (MVA) pathway. The authors then developed an Agrobacterium tumefaciens-mediated transformation (ATMT) method and verified the strength of heterologous promoters in Alternaria alternata TPF6. The authors next transformed the taxadiene-producing platform into A. alternata TPF6, and the MVA pathway was engineered, with introduction of the plant taxadiene-forming gene. Notably, by co-overexpression of isopentenyl diphosphate isomerase (Idi), a truncated version of 3-hydroxy-3-methylglutaryl-CoA reductase (tHMG1), and taxadiene synthase (TS), the authors could detect 61.9 ± 6.3 µg/L taxadiene in the engineered strain GB127. This is the first demonstration of taxadiene production in filamentous fungi, and the approach presented in this study provides a new method for microbial production of Taxol. The well-established ATMT method and the known promoter strengths facilitated further engineering of taxaenes in this fungus.
[Mh] Termos MeSH primário: Alcenos/metabolismo
Diterpenos/metabolismo
Engenharia Metabólica
Ácido Mevalônico/metabolismo
Neoplasias/tratamento farmacológico
[Mh] Termos MeSH secundário: Agrobacterium tumefaciens/genética
Agrobacterium tumefaciens/metabolismo
Alcenos/uso terapêutico
Alternaria/genética
Alternaria/metabolismo
Isomerases de Ligação Dupla Carbono-Carbono/biossíntese
Diterpenos/uso terapêutico
Endófitos/genética
Endófitos/metabolismo
Escherichia coli/genética
Regulação Enzimológica da Expressão Gênica
Proteína HMGB1/biossíntese
Seres Humanos
Isomerases/biossíntese
Transformação Bacteriana/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkenes); 0 (Diterpenes); 0 (HMGB1 Protein); 0 (HMGB1 protein, human); 0 (taxa-4(5),11(12)diene); EC 5.- (Isomerases); EC 5.- (taxa-4(5),11(12)-diene synthase); EC 5.3.3.- (Carbon-Carbon Double Bond Isomerases); EC 5.3.3.2 (isopentenyldiphosphate delta-isomerase); S5UOB36OCZ (Mevalonic Acid)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170428
[Lr] Data última revisão:
170428
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE
[do] DOI:10.1002/biot.201600697


  7 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28125959
[Au] Autor:Veprinskiy V; Heizinger L; Plach MG; Merkl R
[Ad] Endereço:Faculty of Mathematics and Computer Science, University of Hagen, D-58084, Hagen, Germany.
[Ti] Título:Assessing in silico the recruitment and functional spectrum of bacterial enzymes from secondary metabolism.
[So] Source:BMC Evol Biol;17(1):36, 2017 Jan 26.
[Is] ISSN:1471-2148
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Microbes, plants, and fungi synthesize an enormous number of metabolites exhibiting rich chemical diversity. For a high-level classification, metabolism is subdivided into primary (PM) and secondary (SM) metabolism. SM products are often not essential for survival of the organism and it is generally assumed that SM enzymes stem from PM homologs. RESULTS: We wanted to assess evolutionary relationships and function of bona fide bacterial PM and SM enzymes. Thus, we analyzed the content of 1010 biosynthetic gene clusters (BGCs) from the MIBiG dataset; the encoded bacterial enzymes served as representatives of SM. The content of 15 bacterial genomes known not to harbor BGCs served as a representation of PM. Enzymes were categorized on their EC number and for these enzyme functions, frequencies were determined. The comparison of PM/SM frequencies indicates a certain preference for hydrolases (EC class 3) and ligases (EC class 6) in PM and of oxidoreductases (EC class 1) and lyases (EC class 4) in SM. Based on BLAST searches, we determined pairs of PM/SM homologs and their functional diversity. Oxidoreductases, transferases (EC class 2), lyases and isomerases (EC class 5) form a tightly interlinked network indicating that many protein folds can accommodate different functions in PM and SM. In contrast, the functional diversity of hydrolases and especially ligases is significantly limited in PM and SM. For the most direct comparison of PM/SM homologs, we restricted for each BGC the search to the content of the genome it comes from. For each homologous hit, the contribution of the genomic neighborhood to metabolic pathways was summarized in BGC-specific html-pages that are interlinked with KEGG; this dataset can be downloaded from https://www.bioinf.ur.de . CONCLUSIONS: Only few reaction chemistries are overrepresented in bacterial SM and at least 55% of the enzymatic functions present in BGCs possess PM homologs. Many SM enzymes arose in PM and Nature utilized the evolvability of enzymes similarly to establish novel functions both in PM and SM. Future work aimed at the elucidation of evolutionary routes that have interconverted a PM enzyme into an SM homolog can profit from our BGC-specific annotations.
[Mh] Termos MeSH primário: Bactérias/enzimologia
Metabolismo Secundário
[Mh] Termos MeSH secundário: Evolução Biológica
Simulação por Computador
Genoma Bacteriano
Isomerases/genética
Família Multigênica
Oxirredutases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.- (Oxidoreductases); EC 5.- (Isomerases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170128
[St] Status:MEDLINE
[do] DOI:10.1186/s12862-017-0886-2


  8 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28087696
[Au] Autor:Du C; Cao S; Shi X; Nie X; Zheng J; Deng Y; Ruan L; Peng D; Sun M
[Ad] Endereço:From the State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
[Ti] Título:Genetic and Biochemical Characterization of a Gene Operon for -Aconitic Acid, a Novel Nematicide from .
[So] Source:J Biol Chem;292(8):3517-3530, 2017 Feb 24.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:-Aconitic acid (TAA) is an isomer of -aconitic acid (CAA), an intermediate of the tricarboxylic acid cycle that is synthesized by aconitase. Although TAA production has been detected in bacteria and plants for many years and is known to be a potent inhibitor of aconitase, its biosynthetic origins and the physiological relevance of its activity have remained unclear. We have serendipitously uncovered key information relevant to both of these questions. Specifically, in a search for novel nematicidal factors from , a significant nematode pathogen harboring many protein virulence factors, we discovered a high yielding component that showed activity against the plant-parasitic nematode and surprisingly identified it as TAA. Comparison with CAA, which displayed a much weaker nematicidal effect, suggested that TAA is specifically synthesized by as a virulence factor. Analysis of mutants deficient in plasmids that were anticipated to encode virulence factors allowed us to isolate a TAA biosynthesis-related ( ) operon consisting of two genes, and We expressed the corresponding proteins, TbrA and TbrB, and characterized them as an aconitate isomerase and TAA transporter, respectively. Bioinformatics analysis of the TAA biosynthetic gene cluster revealed the association of the TAA genes with transposable elements relevant for horizontal gene transfer as well as a distribution across bacteria and other strains, suggesting a general role for TAA in the interactions of group bacteria with nematode hosts in the soil environment. This study reveals new bioactivity for TAA and the TAA biosynthetic pathway, improving our understanding of virulence factors employed by pathogenesis and providing potential implications for nematode management applications.
[Mh] Termos MeSH primário: Ácido Aconítico/metabolismo
Antinematódeos/metabolismo
Bacillus thuringiensis/enzimologia
Bacillus thuringiensis/genética
Proteínas de Transporte/genética
Isomerases/genética
Óperon
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Bacillus thuringiensis/química
Bacillus thuringiensis/metabolismo
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Proteínas de Transporte/química
Proteínas de Transporte/metabolismo
Elementos de DNA Transponíveis
Genes Bacterianos
Isomerases/química
Isomerases/metabolismo
Família Multigênica
Alinhamento de Sequência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antinematodal Agents); 0 (Bacterial Proteins); 0 (Carrier Proteins); 0 (DNA Transposable Elements); 499-12-7 (Aconitic Acid); EC 5.- (Isomerases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.762666


  9 / 3675 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28041994
[Au] Autor:Shin Y; Moiseyev G; Chakraborty D; Ma JX
[Ad] Endereço:Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.
[Ti] Título:A Dominant Mutation in Rpe65, D477G, Delays Dark Adaptation and Disturbs the Visual Cycle in the Mutant Knock-In Mice.
[So] Source:Am J Pathol;187(3):517-527, 2017 Mar.
[Is] ISSN:1525-2191
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RPE65 is an indispensable component of the retinoid visual cycle in vertebrates, through which the visual chromophore 11-cis-retinal (11-cis-RAL) is generated to maintain normal vision. Various blinding conditions in humans, such as Leber congenital amaurosis and retinitis pigmentosa (RP), are attributed to either homozygous or compound heterozygous mutations in RPE65. Herein, we investigated D477G missense mutation, an unprecedented dominant-acting mutation of RPE65 identified in patients with autosomal dominant RP. We generated a D477G knock-in (KI) mouse and characterized its phenotypes. Although RPE65 protein levels were decreased in heterozygous KI mice, their scotopic, maximal, and photopic electroretinography responses were comparable to those of wild-type (WT) mice in stationary condition. As shown by high-performance liquid chromatography analysis, levels of 11-cis-RAL in fully dark-adapted heterozygous KI mice were similar to that in WT mice. However, kinetics of 11-cis-RAL regeneration after light exposure were significantly slower in heterozygous KI mice compared with WT and RPE65 heterozygous knockout mice. Furthermore, heterozygous KI mice exhibited lower A-wave recovery compared with WT mice after photobleaching, suggesting a delayed dark adaptation. Taken together, these observations suggest that D477G acts as a dominant-negative mutant of RPE65 that delays chromophore regeneration. The KI mice provide a useful model for further understanding of the pathogenesis of RP associated with this RPE65 mutant and for the development of therapeutic strategies.
[Mh] Termos MeSH primário: Adaptação à Escuridão/genética
Técnicas de Introdução de Genes
Genes Dominantes
Mutação/genética
Vias Visuais/metabolismo
cis-trans-Isomerases/genética
[Mh] Termos MeSH secundário: Animais
Cromatografia Líquida de Alta Pressão
Eletrorretinografia
Heterozigoto
Isomerases/metabolismo
Camundongos Mutantes
Modelos Animais
Opsinas/metabolismo
Fotodegradação
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Regeneração
Retina/metabolismo
Retina/patologia
Retinoides/metabolismo
cis-trans-Isomerases/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Opsins); 0 (RNA, Messenger); 0 (Retinoids); EC 3.1.1.64 (retinoid isomerohydrolase); EC 5.- (Isomerases); EC 5.2.- (cis-trans-Isomerases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170529
[Lr] Data última revisão:
170529
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170103
[St] Status:MEDLINE


  10 / 3675 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27899650
[Au] Autor:Reider Apel A; d'Espaux L; Wehrs M; Sachs D; Li RA; Tong GJ; Garber M; Nnadi O; Zhuang W; Hillson NJ; Keasling JD; Mukhopadhyay A
[Ad] Endereço:DOE Joint BioEnergy Institute, Emeryville, California, CA 94608, USA.
[Ti] Título:A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae.
[So] Source:Nucleic Acids Res;45(1):496-508, 2017 Jan 09.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Despite the extensive use of Saccharomyces cerevisiae as a platform for synthetic biology, strain engineering remains slow and laborious. Here, we employ CRISPR/Cas9 technology to build a cloning-free toolkit that addresses commonly encountered obstacles in metabolic engineering, including chromosomal integration locus and promoter selection, as well as protein localization and solubility. The toolkit includes 23 Cas9-sgRNA plasmids, 37 promoters of various strengths and temporal expression profiles, and 10 protein-localization, degradation and solubility tags. We facilitated the use of these parts via a web-based tool, that automates the generation of DNA fragments for integration. Our system builds upon existing gene editing methods in the thoroughness with which the parts are standardized and characterized, the types and number of parts available and the ease with which our methodology can be used to perform genetic edits in yeast. We demonstrated the applicability of this toolkit by optimizing the expression of a challenging but industrially important enzyme, taxadiene synthase (TXS). This approach enabled us to diagnose an issue with TXS solubility, the resolution of which yielded a 25-fold improvement in taxadiene production.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Sistemas CRISPR-Cas
DNA Fúngico/genética
Endonucleases/genética
Engenharia Genética/métodos
RNA Guia/genética
Saccharomyces cerevisiae/genética
[Mh] Termos MeSH secundário: Proteínas de Bactérias/metabolismo
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
DNA Fúngico/metabolismo
Endonucleases/metabolismo
Expressão Gênica
Isomerases/genética
Isomerases/metabolismo
Plasmídeos/química
Plasmídeos/metabolismo
Regiões Promotoras Genéticas
RNA Guia/metabolismo
Saccharomyces cerevisiae/metabolismo
Software
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (DNA, Fungal); 0 (RNA, Guide); EC 3.1.- (Cas9 endonuclease Streptococcus pyogenes); EC 3.1.- (Endonucleases); EC 5.- (Isomerases); EC 5.- (taxa-4(5),11(12)-diene synthase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161201
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkw1023



página 1 de 368 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde