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PROVIDER: PRJNA1300595 | ENA |
REPOSITORIES: ENA
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Project description:Optimization of microbial production is essential for the application of synthetic biology in industrial and sustainable biosynthesis. β-carotene is a high-value compound that can be heterologously produced in budding yeast Saccharomyces cerevisiae, providing an alternative to natural extraction. However, intelligent design of strain and process to reduce the production cost remains a great challenge. In this study, we aimed to enhance β-carotene production by integrating systems biology and machine learning-guided strain design of the β-carotene-producing yeast. We identified transcriptional alterations in the β-carotene-producing yeast including genes associated iron deficiency, while no significant changes in the mevalonate (MVA) pathway. We then fine-tuned gene expression of rate-limiting enzymes in the mevalonate pathway through combinatorial construction of promoters and terminators. XGBoost training was applied in the DBTL cycle to facilitate rapid optimization. In the second DBTL cycle, fine-tuning MVA gene expression resulted in a 139% improvement in β-carotene titer. We then supplemented β-carotene production with iron, guided by transcriptional insights in alternations of genes related to iron uptake in β-carotene-producing yeast, resulting in an 70.54% improvement in β-carotene titer at 48 hours. Moreover, integrating the fine-tuned MVA cassette with iron supplementation yielded up to 72.07 mg/L of β-carotene at 72 hours, representing a 67.79% increase compared to that of the parent strain without MVA gene adjustments and iron supplementation. Our study highlights the potential of combining machine learning and omics approaches with synthetic biology to enhance non-native biochemical production in yeast.
2026-08-03 | GSE288397 | GEO
Project description:We develop a CRISPR-Cas assisted random mutation (CARM) technology for whole genome mutagenesis. As a proof-of-principle, CARM was applied to evolve the capacity of Saccharomyces cerevisiae to produce β-carotene. Thees files are transcriptomic analysis of finally evolutionary strain C7-143, processed evolutionary strain C3-06 and C5-63, and the original strains C0 and BY47419.
2020-11-26 | GSE162126 | GEO
Project description:Atherosclerosis is characterized by the pathological accumulation of cholesterol-laden macrophages in the arterial wall. Atherosclerosis is also the main underlying cause of cardiovascular diseases (CVDs), and its development is largely driven by elevated plasma cholesterol. Strong epidemiological data find an inverse association between plasma β-carotene with atherosclerosis, and we recently showed that β-carotene oxygenase 1 (BCO1) activity, responsible for β-carotene cleavage to vitamin A, is associated with reduced plasma cholesterol in humans and mice. In this study, we explore whether intact β-carotene or vitamin A affect atherosclerosis progression in the atheroprone low-density lipoprotein receptor (LDLR) - deficient mice. In comparison to control-fed Ldlr-/- mice, β-carotene-supplemented mice showed reduced atherosclerotic lesion size at the level of the aortic root and plasma cholesterol levels (P = 0.0003). These changes were absent in Ldlr-/-/Bco1-/- mice, despite accumulating β-carotene in plasma and atherosclerotic lesions. We discarded the implication of myeloid BCO1 in the development of atherosclerosis by performing bone marrow transplant experiments. Lipid production assays found that retinoic acid, the active form of vitamin A, reduced the secretion of newly synthetized triglyceride and cholesteryl ester in cell culture and mice. Overall, our findings provide insights into the role of BCO1 activity and vitamin A in atherosclerosis progression through the regulation of hepatic lipid metabolism.
2020-11-12 | GSE157972 | GEO
Project description:Saccharomyces cerevisiae is an excellent microorganism for industrial succinic acid production, but high succinic acid concentration will inhibit the growth of Saccharomyces cerevisiae then reduce the production of succinic acid. Through analysis the transcriptomic data of Saccharomyces cerevisiae with different genetic backgrounds under different succinic acid stress, we hope to find the response mechanism of Saccharomyces cerevisiae to succinic acid.
2022-01-09 | GSE193190 | GEO
Project description:Soybeans (Glycine max) were genetically modified using a gene gun to produce beta-carotene, which is not normally found in the species. beta-carotene is produced in the chloroplast in which it competes with chlorophyl for production. A proteomics analysis was performed to determine the effects of the transgene on seed protein content.
2016-07-19 | PXD000709 | Pride
Project description:In this study, β-carotene concentrations in cassava storage roots were enhanced by co-expression of transgenes for deoxyxylulose-5-phosphate synthase (DXS) and bacterial phytoene synthase (crtB), mediated by the patatin type-1 promoter. Storage roots harvested from field-grown plants accumulated carotenoids to ≤50 μg/g DW, a 15- to 20-fold increase relative to roots from non-transgenic plants. Approximately 85-90% of these carotenoids accumulated as all-trans-β-carotene, the most nutritionally efficacious carotenoid. β-carotene-accumulating storage roots displayed delayed onset of post-harvest physiological deterioration, a major constraint limiting utilization of cassava products. Significant metabolite changes were detected in β-carotene enhanced storage roots. Most significantly, an inverse correlation was observed between β-carotene and dry matter contents, with reductions of 50% to 60% of dry matter content in the highest carotenoid accumulating storage roots of different cultivars. Further analysis confirmed concomitant reduction in starch content, and increased levels of total fatty acids, triacylglycerols, soluble sugars, and abscisic acid. Irish potato engineered to co-express DXS and crtB displayed a similar correlation between β-carotene accumulation, reduced dry matter and starch content, and elevated oil and soluble sugars in tubers. Transcriptome analyses revealed reduced expression of starch biosynthetic genes, ADP-glucose pyrophosphorylase genes, in transgenic, carotene-accumulating cassava roots relative to non-transgenic roots. These findings highlight unintended metabolic consequences of provitamin A biofortification of starch-rich organs and point to strategies for redirecting metabolic flux to restore starch production.
2017-06-22 | GSE100319 | GEO
Project description:To obtain insight in the genome-wide response of heterologous carotenoid production in Saccharomyces cerevisiae, we have analyzed the transcriptome of S. cerevisiae strains overexpressing carotenogenic genes from the yeast Xanthophyllomyces dendrorhous. For this purpose, two strains producing different levels of carotenoids were grown in carbon-limited continuous cultures and genome-wide expression was analyzed. The strain producing low carotenoid levels did not exhibit a clear genome-wide transcriptional response, suggesting that low carotenoid levels do not result in cellular stress. Transcriptome analysis of a strain producing high carotenoid levels resulted in specific induction of genes involved in pleiotropic drug resistance (PDR). These genes encode ATP-binding cassette (ABC) type transporters and major facilitator transporters which are involved in secretion of toxic compounds out of cells. Our results suggest that production of high amounts of carotenoids in S. cerevisiae lead to toxicity and that these cells are prone to secrete carotenoids out of the cell. Indeed, secretion of beta-carotene into sunflower oil was observed upon addition of this hydrophobic solvent to the growth medium. Finally, it was observed that deletion of the ABC transporter pdr10, one of the induced PDR transporters, highly decreased the transformation efficiency of an episomal vector containing carotenogenic genes. The few colored transformants that were obtained had decreased growth rates and lower carotenoid production levels compared to control strains transformed with the same carotenogenic genes. These results indicate that Pdr10 might be specifically involved in carotenoid tolerance in S. cerevisiae strains. Keywords: dose response
2008-06-01 | GSE8451 | GEO
Project description:Purpose: According to comparative transcriptomes data, the differentially expressed genes within these selected scrambled yeast strains can be digged out and further analyzed, seeking potential targets that were tuned drastically and might improve β-carotene production when modified. Methods: mRNA profiles of two Saccharomyces cerevisiae strains H0, S3 (each named as yJBH000 and yJBH012 in related manuscript) were generated in triplicate using illumina. Sequencing libraries were generated using NEBNext® Ultra™ RNA Library Prep Kit for Illumina® (NEB, USA) and index codes were added to each sample. The library preparations were sequenced on an Illumina Hiseq 4000 platform. 150 bp paired-end reads were generated as raw data. The read counts for each gene in the genome were summarized as processed data. Results: The yJBH012 had an obviously different pattern of global transcription as compared with the control yJBH000. The upregulation of 589 genes and down regulation of 236 genes were observed in this analysis.
2019-05-22 | GSE108580 | GEO
Project description:Industrial bioethanol production may involve a low pH environment,improving the tolerance of S. cerevisiae to a low pH environment caused by inorganic acids may be of industrial importance to control bacterial contamination, increase ethanol yield and reduce production cost. Through analysis the transcriptomic data of Saccharomyces cerevisiae with different ploidy under low pH stress, we hope to find the tolerance mechanism of Saccharomyces cerevisiae to low pH.
2022-12-09 | GSE210964 | GEO
Project description:To obtain insight in the genome-wide response of heterologous carotenoid production in Saccharomyces cerevisiae, we have analyzed the transcriptome of S. cerevisiae strains overexpressing carotenogenic genes from the yeast Xanthophyllomyces dendrorhous. For this purpose, two strains producing different levels of carotenoids were grown in carbon-limited continuous cultures and genome-wide expression was analyzed. The strain producing low carotenoid levels did not exhibit a clear genome-wide transcriptional response, suggesting that low carotenoid levels do not result in cellular stress. Transcriptome analysis of a strain producing high carotenoid levels resulted in specific induction of genes involved in pleiotropic drug resistance (PDR). These genes encode ATP-binding cassette (ABC) type transporters and major facilitator transporters which are involved in secretion of toxic compounds out of cells. Our results suggest that production of high amounts of carotenoids in S. cerevisiae lead to toxicity and that these cells are prone to secrete carotenoids out of the cell. Indeed, secretion of ï¢-carotene into sunflower oil was observed upon addition of this hydrophobic solvent to the growth medium. Finally, it was observed that deletion of the ABC transporter pdr10, one of the induced PDR transporters, highly decreased the transformation efficiency of an episomal vector containing carotenogenic genes. The few colored transformants that were obtained had decreased growth rates and lower carotenoid production levels compared to control strains transformed with the same carotenogenic genes. These results indicate that Pdr10 might be specifically involved in carotenoid tolerance in S. cerevisiae strains. Experiment Overall Design: The genome wide transcriptional response of S. cerevisiae cells that heterologously produce carotenoids might provide information concerning the impact of carotenoid production on yeast physiology and might identify bottlenecks relevant for the production of these compounds. DNA microarray experiments have been proven to be a powerful tool to study the genome wide transcriptional response of S. cerevisiae to changes of the physiological state and the environment (for example 3,. Genomics approaches on cells producing heterologous metabolites to study their impact on yeast physiology have not been reported yet for S. cerevisiae. Additionally, most transcriptome studies with S. cerevisiae have been performed with cells grown in shake flasks cultures. The main drawback of shake flask cultivation is that the environment is continuously changing, which may be of high influence on carotenoid production, and interpretation of transcriptome data . Chemostat cultivation offers advantages for studies with DNA microarrays because it enables cultivation of microorganisms under tightly defined environmental conditions. An interlaboratory comparison of transcriptome data obtained in chemostat cultures has indeed demonstrated that the accuracy and reproducibility of this approach are superior to those obtained in previous studies with shake-flask cultures .
2008-06-18 | E-GEOD-8451 | biostudies-arrayexpress