Transcriptome of the geldanamycin producer Streptomyces hygroscopicus XM201
Ontology highlight
ABSTRACT:
ORGANISM(S): Streptomyces hygroscopicus
PROVIDER: GSE92334 | GEO | 2017/03/03
SECONDARY ACCESSION(S): PRJNA357258
REPOSITORIES: GEO
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Project description:The statsitcal model, latent pathway identification analysis (LPIA), was implemented for the analysis of A549 lung carcinoma cells treated with geldanamycin. Control and treated samples were assayed with Affymetrix HG_U133_plus_2 arrays and analyzed using LPIA. LPIA looks for statistically signficant evidence of dysregulation in a network of pathways constructed in a manner that explicitly links pathways through their common function in the cell. Geldanamycin (geld) is known to inhibit the molecular chaperone protein, Hsp90, and plays a role in preventing the malignant transformation and proliferation of healthy cells during oncogenesis. LPIA successfully identified pathways specific to geldanamycin effects at the gene transcription level.
2011-01-11 | GSE26525 | GEO
Project description:The statsitcal model, latent pathway identification analysis (LPIA), was implemented for the analysis of A549 lung carcinoma cells treated with geldanamycin. Control and treated samples were assayed with Affymetrix HG_U133_plus_2 arrays and analyzed using LPIA. LPIA looks for statistically signï¬cant evidence of dysregulation in a network of pathways constructed in a manner that explicitly links pathways through their common function in the cell. Geldanamycin (geld) is known to inhibit the molecular chaperone protein, Hsp90, and plays a role in preventing the malignant transformation and proliferation of healthy cells during oncogenesis. LPIA successfully identified pathways specific to geldanamycin effects at the gene transcription level. A549 lung carcinoma cells were allowed to adhere for 24h and further incubated in the presence of geldanamycin at a concentration equivalent to the determined IC50 of 40 nM or IC20 of 10 nM, or with vehicle DMSO (final concentration 0.4%). After 24h and 48 h, cells were harvested and total RNA was purified and processed for Affymetrix HG_U133_Plus_2.0 microarray analysis. Raw probe intensities were RMA-normalized and avereaged for three replicates for each condition. Probe sets for 54,120-annotated open reading frames were included in LPIA analysis.
2011-01-11 | E-GEOD-26525 | biostudies-arrayexpress
Project description:Effect of heat shock or HSP90 inhibitors (geldanamycin and radicicol) on wild type Arabidopsis thaliana.
2007-06-01 | E-ATMX-12 | biostudies-arrayexpress
Project description:The taxonomy of an actinobacterial strain, designated JJY4T, was established using a polyphasic approach. JJY4T was isolated from the rhizosphere of Chromolaena odorata in Yaoundé (Cameroon) during a project for the selection of biological control agents. Strain JJY4T exhibited antimicrobial activities against bacteria, fungi, and oomycetes. Strain JJY4T also exhibited the traits of plant growth-promoting rhizobacteria such as the solubilization of inorganic phosphate, production of siderophores and indole-3-acetic acid, and 1-aminocyclopropane-1-carboxylate deaminase activity. In planta assays performed on cocoa plantlets confirmed that strain JJY4T exhibited strong abilities to promote plant growth and protect against Phytophthora megakarya, the main causal agent of cocoa pod rot. The formation of rugose-ornamented spores in spiral spore chains by strain JJY4T is a typical feature of members found in the Streptomyces violaceusniger clade and, similar to some members of the clade, strain JJY4T produces geldanamycin. A phylogenetic analysis based on 16S rRNA gene sequences confirmed this classification and suggests that strain JJY4T be added to the subclade constituted of the type strains Streptomyces malaysiensis DSM 41697T and Streptomyces samsunensis DSM 42010T. However, DNA-DNA relatedness and physiological characteristics allowed for the differentiation of strain JJY4T from its closest phylogenetic relatives. Based on these results, strain JJY4T (=NRRL B-65369, =NBRC 112705) appears to represent a novel species in the S. violaceusniger clade for which the proposed name is Streptomyces cameroonensis sp. nov.
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Project description:Due to its aquatic saprophytic lifestyle, the fungus Blastocladiella emersonii seems to be adapted to low aerated environments and thus can be an interesting model of study of the hypoxic stress response. Iron deprivation, a hypoxia-mimicking stimulus due to HIF-1 stabilization, and geldanamycin, that causes HIF-1 depletion by HSP90 inhibition, are helpful parameters to find an evidence of an oxygen-dependent regulatory mechanism in B. emersonii similar to the metazoan HIF-1 pathway.
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Project description:Due to its aquatic saprophytic lifestyle, the fungus Blastocladiella emersonii seems to be adapted to low aerated environments and thus can be an interesting model of study of the hypoxic stress response. Iron deprivation, a hypoxia-mimicking stimulus due to HIF-1 stabilization, and geldanamycin, that causes HIF-1 depletion by HSP90 inhibition, are helpful parameters to find an evidence of an oxygen-dependent regulatory mechanism in B. emersonii similar to the metazoan HIF-1 pathway. Direct transcript comparison between cells grown under normoxic conditions (70%sat. O2 in air) and cells submitted to oxygen deprivation (direct and gradual) and iron (II) deprivation. It was also compared transcripts of cells submitted to direct 1-hour hypoxia (1%sat. O2) with cells treated with geldanamycin for 1 hour, followed to 1-hour hypoxia (1%sat. O2). There are at least 3 biological replicates (independent harvest) and 2 technical replicates of each array (L - left and R - right).
2010-06-24 | E-GEOD-17524 | biostudies-arrayexpress
Project description:<p>Natural products from microorganisms are important sources for drug discovery. With the development of high-throughput sequencing technology and bioinformatics, a large amount of uncharacterized biosynthetic gene clusters (BGCs) in microorganisms have been found, which show the potential for novel natural product production. 9 BGCs containing PKS and/or NRPS in <em>Streptomyces globisporus</em> C-1027 were transcriptionally low/silent under the experimental fermentation conditions, and the products of these clusters are unknown. Thus, we tried to activate these BGCs to explore cryptic products of this strain. We constructed the cluster-situated regulator overexpressing strains which contained regulator gene(s) under the control of the constitutive promoter <em>ermE</em>*p in <em>S. globisporus</em> C-1027. Overexpression of regulators in cluster 26 resulted in significant transcriptional upregulation of biosynthetic genes. With the separation and identification of products from the overexpressing strain OELuxR1R2, 3 <em>ortho</em>-methyl phenyl alkenoic acids (compounds <strong>1-3</strong>) were obtained. Gene disruption showed that compounds <strong>1</strong> and <strong>2</strong> were completely abolished in the mutant GlaEKO, but were hardly affected by deletion of the genes <em>orf3</em> or <em>echA</em> in cluster 26. The type II PKS biosynthetic pathway of chain-extended cinnamoyl compounds was deduced by bioinformatics analysis. This study showed that overexpression of the 2 adjacent cluster-situated LuxR regulator(s) is an effective strategy to connect the orphan BGC to its products.</p>
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Project description:Protein kinases (PKs) are involved in plant growth and stress responses, and constitute one of the largest superfamilies due to numerous gene duplications. However, limited PKs have been functionally described in pecan, an economically important nut tree. Here, the comprehensive identification, annotation and classification of the entire pecan kinome was reported. A total of 967 PK genes were identified from pecan genome, and further classified into 20 different groups and 121 subfamilies using the kinase domain sequences, which were verified by the phylogenetic analysis. The receptor-like kinase (RLK) group contained 565 members, which constituted the largest group. Gene duplication contributed to the expansion of pecan kinome, 169 duplication events including 285 PK genes were found, and Ka/Ks ratio revealed they experienced strong negative selection. GO functional analysis indicated majority PKs involved in molecular functions and biological processes. The RNA-Seq data of PK genes in pecan were further analyzed at subfamily level, and different PK subfamilies performed various expression patterns across different conditions or treatments, suggesting PK genes in pecan involved in multiple biological functions and stress responses. Taken together, this study provided insight into the expansion, evolution and function of pecan PKs. Our findings regarding expansion, expression and co-expression analyses could lay a good foundation for future research to understand the roles of pecan PKs, and find the key candidate genes more efficiently.
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Project description:In submerged cultivation of filamentous microbes, including actinomycetes, complex morphology is one of the critical process features for secondary metabolites production. Ansamitocin P-3 (AP-3), an antitumor agent, is a secondary metabolite produced by Actinosynnema pretiosum ATCC 31280. An excessive mycelial fragmentation of A. pretiosum ATCC 31280 was observed during the early stage of fermentation. In order to identify genes involved in the early mycelial fragmentation, the total RNAs of mycelia collected at 15, 18, and 24 h were extracted and subjected to transcriptome sequencing using RNA-seq technology.Through comparative transcriptomic analysis, a subtilisin-like serine peptidase encoded gene APASM_4178 was identified to be responsible for the mycelial fragmentation. Mutant WYT-5 with the APASM_4178 deletion showed increased biomass and improved AP-3 yield by 43.65%.
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Project description:Goblet cell metaplasia and mucus hypersecretion are disabling hallmarks of chronic lung diseases for which no curative treatments are available. Therapies targeting specific upstream drivers of asthma have had variable results. We hypothesized that an a priori-knowledge independent approach would point to new therapies for airway goblet cell metaplasia. We analyzed the transcriptome of an organotypic model of human goblet cell metaplasia. We combined our data with previously published datasets from IL13-exposed in vitro and asthmatic in vivo human airway epithelial cells. The drug perturbation-response connectivity approach identified the heat shock protein 90 (HSP90) inhibitor geldanamycin as a candidate for reverting airway goblet cell metaplasia. We found that geldanamycin not only prevented but reverted IL13-induced goblet cell metaplasia. Geldanamycin did not induce goblet cell death, did not solely block mucin synthesis, and did not block IL13 receptor-proximal signaling. Moreover, the transcriptional effects of geldanamycin were absent in unstimulated cells and became evident only after stimulation with IL13. The predicted mechanism of action suggested that geldanamycin should also revert IL17-induced goblet cell metaplasia, a prediction confirmed by our data. Our findings suggest HSP90 activity may be required for persistence of goblet cell metaplasia driven by various mechanisms in chronic lung diseases.
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