Combinatorial effect of ARTP mutagenesis and ribosome engineering on an industrial Streptomyces albus strain S12 for enhanced biosynthesis of salinomycin
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ABSTRACT:
PROVIDER: PRJNA551961 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9622380.fastq.gz | Fastqsanger.gz | |||
| SRR9622381.fastq.gz | Fastqsanger.gz | |||
| SRR9622382.fastq.gz | Fastqsanger.gz |
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Project description:Streptomyces albus S12, TK and Tet30Chl25 are the parental strain , low-yield and high-yield of salinomycin mutant obtained by ARTP and ribosome engineering ,respectively. There are total 1602 differentially expressed genes (DEGs) show differences in expression between the mutant strain TK, Tet30Chl25 and the initial strain S12. KEGG pathway analysis of differentially expressed genes (DEGs) between the mutant strain TK, Tet30Chl25 and the initial strain S12 show that the relevant differential pathways affecting salinomycin production were mainly related to butanoate metabolism, starch and sucrose metabolism, glyoxylate metabolism. Besides , the transcription of genes in the salinomycin biosynthesis gene cluster and the transcription level of related genes in the precursors biosynthesis pathway were more active in the high-yield salinomycin production strain Tet30Chl25. Furthermore, the transcription level ribosomal protein, string response, two component system and sigma factors are more active in high-yield of salinomycin mutants and that may involve in regulation of salinomycin biosynthesis and may account for the high-yield of salinomycin.
2019-10-01 | GSE133580 | GEO
Project description:Salinomycin, an important polyketide, has been widely utilized in agriculture to inhibit growth of pathogenic bacteria. In addition, salinomycin has great potential in treatment of cancer cells. Due to inherited characteristics and beneficial potential, its demand is also inclining. Therefore, there is an urgent need to increase the current high demand of salinomycin. In order to obtain a high-yield mutant strain of salinomycin, the present work has developed an efficient breeding process of Streptomyces albus by using atmospheric and room temperature plasma (ARTP) combined with ribosome engineering. In this study, we investigate the presented method as it has the advantage of significantly shortening mutant screening duration by using an agar block diffusion method, as compared to other traditional strain breeding methods. As a result, the obtained mutant Tet30Chl25 with tetracycline and chloramphenicol resistance provided a salinomycin yield of 34,712 mg/L in shake flask culture, which was over 2.0-fold the parental strain S12. In addition, comparative transcriptome analysis of low and high yield mutants, and a parental strain revealed the mechanistic insight of biosynthesis pathways, in which metabolic pathways including butanoate metabolism, starch and sucrose metabolism and glyoxylate metabolism were closely associated with salinomycin biosynthesis. Moreover, we also confirmed that enhanced flux of glyoxylate metabolism via overexpression gene of isocitrate lyase (icl) promoted salinomycin biosynthesis. Based on these results, it has been successfully verified that the overexpression of crotonyl-CoA reductase gene (crr) and transcriptional regulator genes (orf 3 and orf 15), located in salinomycin synthesis gene cluster, is possibly responsible for the increase in salinomycin production in a typical strain Streptomyces albus DSM41398. Conclusively, a tentative regulatory model of ribosome engineering combined with ARTP in S. ablus is proposed to explore the roles of transcriptional regulators and stringent responses in the biosynthesis regulation of salinomycin.
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Project description:Bulk RNA-seq data of alisertib induced senescent cells treated with Salinomycin vs. Untreated
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Project description:Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We show that salinomycin is able to decrease cell viability and induce apoptosis. In combination with the chemotherapeutic agents cisplatin and paclitaxel, salinomycin synergistically killed HNSCC cancer stem cells more effectively than either drug alone. Furthermore, we observed that salinomycin decreases stem cell properties as shown by a significant reduction in sphere formation and a decrease of both CD44 and BMI-1. Contrary to expectations, salinomycin caused an induction of EMT as shown by an increase in Snail and Vimentin, and a decrease in E-cadherin expression. Even though EMT was induced, salinomycin caused a decrease in invasion through a membrane. In search of a possible mechanism, the effects on the Akt pathway were explored. Interestingly, salinomycin also induced phosphorylation of Akt. Activation of EMT and Akt are both tightly associated with an increase in stemness, which brings to question the relationship between CSCs and these two fundamental pathways. Taken together, our findings indicate that salinomycin shows promise as a novel treatment for HNSCC despite an activation of EMT and Akt. MicroRNA obtained from JLO-1 cells treated for 48 hours in varying doses of salinomycin. Changes in microRNA expression are analyzed by normalizing expression values with the control sample.
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Project description:Here, we established a successive Fe0-enhanced microbe system to remove azo dye (a typical organic pollutant) by Shewanella decolorationis S12 (S. decolorationis S12, an effective azo dye degradation bacterium) and examined the gene expression time course (10, 30, 60, and 120 min) in whole genome transcriptional level. Comparing with the treatment without ZVI, approximately 8% genes affiliated with 10 different gene expression profiles in S. decolorationis S12 were significantly changed in 120 min during the ZVI-enhanced microbial azo reduction. Intriguingly, MarR transcriptional factor might play a vital role in regulating ZVI-enhanced azo reduction in the aspect of energy production, iron homeostasis, and detoxification. Further investigation showed that induced [Ni-Fe] H2ase genes (hyaABCDEF) and azoreductase genes (mtrABC-omcA) contributed to ZVI-enhanced energy production, while reduced iron uptake (hmuVCB and feoAB), induced sulfate assimilation (cysPTWA) and cysteine biosynthesis (cysM) related genes were essential to iron homeostasis and detoxification. This study disentangles underlying mechanisms of ZVI-enhanced azo reduction in S. decolorationis S12 and lays a foundation for further optimization of integrated ZVI-microbial system for efficient organic pollution treatment.
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Project description:Screens for agents that specifically kill epithelial cancer stem cells (CSCs) have not been possible due to the rarity of these cells within tumor cell populations and their relative instability in culture. We describe here an approach to screening for agents with epithelial CSC-specific toxicity. We implemented this method in a chemical screen and discovered compounds showing selective toxicity for breast CSCs. One compound, salinomycin, reduces the proportion of CSCs by >100-fold relative to paclitaxel, a commonly used breast cancer chemotherapeutic drug. Treatment of mice with salinomycin inhibits mammary tumor growth in vivo and induces increased epithelial differentiation of tumor cells. In addition, global gene expression analyses show that salinomycin treatment results in the loss of expression of breast CSC genes previously identified by analyses of breast tissues isolated directly from patients. This study demonstrates the ability to identify agents with specific toxicity for epithelial CSCs Experiment Overall Design: Experimentally transformed HMLER breast cancer cells were treated in culture with either paclitaxel (10nM) or salinomycin (1uM) for one week. There were three biologic replicates for each treatment condition.
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Project description:Cancer stem cells are believed to play a crucial role in cancer recurrence due to their resistance to conventional chemotherapy and capacity for self-renewal. Recent studies have reported that salinomycin, a livestock antibiotic, selectively targets breast cancer stem cells 100-fold more effectively than paclitaxel. In our study we sought to determine the effects of salinomycin on head and neck squamous cell carcinoma (HNSCC) stem cells. We show that salinomycin is able to decrease cell viability and induce apoptosis. In combination with the chemotherapeutic agents cisplatin and paclitaxel, salinomycin synergistically killed HNSCC cancer stem cells more effectively than either drug alone. Furthermore, we observed that salinomycin decreases stem cell properties as shown by a significant reduction in sphere formation and a decrease of both CD44 and BMI-1. Contrary to expectations, salinomycin caused an induction of EMT as shown by an increase in Snail and Vimentin, and a decrease in E-cadherin expression. Even though EMT was induced, salinomycin caused a decrease in invasion through a membrane. In search of a possible mechanism, the effects on the Akt pathway were explored. Interestingly, salinomycin also induced phosphorylation of Akt. Activation of EMT and Akt are both tightly associated with an increase in stemness, which brings to question the relationship between CSCs and these two fundamental pathways. Taken together, our findings indicate that salinomycin shows promise as a novel treatment for HNSCC despite an activation of EMT and Akt.
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