Transcriptomic analysis of engineered and improved Pichia pastoris for S-adenosyl-l-methionine (SAM) production
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PROVIDER: PRJNA464437 | ENA |
REPOSITORIES: ENA
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Project description:SAM is the principal methyl group donor in all living organisms, and has attracted much interest in clinical research. We improved SAM production in engineered P. pastoris strain GS115/DS56 by overexpression of the recombinant methionine adenosyltransferase (MAT) gene DS56, and further enhanced SAM prduction in G12-CBS by downregulation of the cystathionine β-synthase (CBS) gene CYS4 with a weak promoter G12. We performed the pairwise transcriptome comparisons between high-producing (HP) and low-producing (LP) strains, in order to understand the impact of SAM accumulation on the P. pastoris physiology and to identify genome-wide targets for further improving SAM production.
2018-09-01 | GSE114152 | GEO
Project description:Comparison of transcription profile of Pichia pastoris cells grown on Glucose medium with Pichia pastoris cells grown on Methanol/Glycerol medium, the fermentations were done in a chemostat.
2015-08-31 | GSE67690 | GEO
Project description:Comparison of transcription profile of Pichia pastoris cells grown on Glucose medium with Pichia pastoris cells grown on Methanol/Glycerol medium, the fermentations were done in a chemostat. 2 color experiment in reference design. Pichia pastoris reference mix [mixed pool of Pichia pastoris cells sampled from various conditions including cells grown on glycerine, glucose and methanol, on full andminimal medium, in stationary and exponential growth phase, and in different stress states]
2015-08-31 | E-GEOD-67690 | biostudies-arrayexpress
Project description:Epigenetics (DNA methylation) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl
2016-02-02 | GSE74081 | GEO
Project description:Background: Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Methods: Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes. Additionally, mass spectrometry analysis revealed that Venetoclax (VEN), a BCL-2 inhibitor recently approved by the FDA for AML treatment, significantly decreases the intracellular level of methionine in AML cells. Based on these findings, we hypothesized that combining 8CA or 8AA with VEN can efficiently target the Methionine-MAT2A-S-adenosyl-methionine (SAM) axis in AML. Results: Our results demonstrate that VEN and 8CA/8AA synergistically decrease the SAM biosynthesis and effectively target AML cells both in vivo and in vitro. Conclusions: These findings suggest the promising potential of combining 8CA/8AA and VEN for AML treatment by inhibiting Methionine-MAT2A-SAM axis and provide a strong rationale for our recently activated clinical trial.
2023-11-09 | GSE247025 | GEO
Project description:Over the past three decades, due to the universal application of Pichia yeast in the fermentation industry as well as the establishment of Pichia pastoris fermentation process for more than 30 years, the technology of the whole process has become very mature and has now reached a stagnated period of growth. However, studies and research conducted on the genomics of the classic fermentation process and the uncovering of the biological phenomena in the fermentation process from the point of view of high-throughput gene or protein is still in its early stages, and there is still insufficient data within this field. First, in collaboration with Agilent Company, we designed and prepared an expression microarray that could be used for the detection of Pichia pastoris transcriptomics. The transcriptomic changes in the five key technology steps (time points), during the fermentation process of Pichia pastoris would then be detected with the aid of an expression microarray. The five key steps of technology described above formed two important biological processes, namely, the limiting carbon source replacement and secondly, the fermentative production of exogenous proteins. The biological phenomena involved in these two processes were displayed and analyzed at the transcriptional level. In addition to this, with regard to the most important function in the fermentation process of Pichia pastoris, oxid-reduction, the metabolic drift process was analyzed and the important genes that might dominate the changes in the metabolic flux were discovered creatively by using the function tree method in this paper. This study was undertaken from the point of view of the transcriptome and the biological phenomena in the fermemntation process of Pichia pastoris. Both of which, were thoroughly explained during this study. The hope is for many more researchers to optimize the strain fermentation process, to produce proteins at the genetic level, as well as providing and obtaining new perspectives and detailed scientific data for the continued development within this field.
2014-04-18 | GSE56873 | GEO
Project description:Transcriptional profiling of Pichia pastoris cultivated at different specific growth rates in carbon and energy-limited aerobic chemostats and retentostats
2016-05-10 | GSE81070 | GEO
Project description:The SIN3 histone modifying complex regulates the expression of multiple methionine catabolic genes including SAM synthetase (Sam-S) as well as the level of S-adenosyl-methionine (SAM). To further investigate the relationship between methionine catabolism and epigenetic regulation by SIN3, we identified genes controlled by SIN3 and SAM-S. As a global transcriptional regulator, SIN3 impacted a wide range of genes. Independently, SAM-S affected a narrow range of genes. Additional genes, however, were influenced in dual knockdown cells. At some genes, SIN3 and SAM-S act independently, for others, redundantly and for a third set, in opposition. Together, the results obtained in the study of SIN3, a cofactor associated with histone modification, and SAM-S, a metabolic enzyme, uncover a complex relationship on regulating transcription.
2019-11-26 | GSE129145 | GEO
Project description:Over the past three decades, due to the universal application of Pichia yeast in the fermentation industry as well as the establishment of Pichia pastoris fermentation process for more than 30 years, the technology of the whole process has become very mature and has now reached a stagnated period of growth. However, studies and research conducted on the genomics of the classic fermentation process and the uncovering of the biological phenomena in the fermentation process from the point of view of high-throughput gene or protein is still in its early stages, and there is still insufficient data within this field. First, in collaboration with Agilent Company, we designed and prepared an expression microarray that could be used for the detection of Pichia pastoris transcriptomics. The transcriptomic changes in the five key technology steps (time points), during the fermentation process of Pichia pastoris would then be detected with the aid of an expression microarray. The five key steps of technology described above formed two important biological processes, namely, the limiting carbon source replacement and secondly, the fermentative production of exogenous proteins. The biological phenomena involved in these two processes were displayed and analyzed at the transcriptional level. In addition to this, with regard to the most important function in the fermentation process of Pichia pastoris, oxid-reduction, the metabolic drift process was analyzed and the important genes that might dominate the changes in the metabolic flux were discovered creatively by using the function tree method in this paper. This study was undertaken from the point of view of the transcriptome and the biological phenomena in the fermemntation process of Pichia pastoris. Both of which, were thoroughly explained during this study. The hope is for many more researchers to optimize the strain fermentation process, to produce proteins at the genetic level, as well as providing and obtaining new perspectives and detailed scientific data for the continued development within this field. The transcriptomic changes in the five key technology steps (time points), during the fermentation process of Pichia pastoris would then be detected with the aid of an expression microarray.
2014-04-18 | E-GEOD-56873 | biostudies-arrayexpress
Project description:The regulation of gene expression in Pichia pastoris has so far involved study of transcription factors. However, there are factors other than transcription factors affecting mRNA synthesis such as coactivators, enhancers, and chromatin modifiers. This study is a first ever report on epigenetic regulation in Pichia pastoris where, a histone acetyltransferase is reported to regulate transcription of genes involved in utilization of alternate carbon sources. We employed RNA Seq to identify new targets of Gcn5 in methanol medium.
2022-12-31 | GSE150467 | GEO