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PROVIDER: PRJNA1154455 | ENA |
REPOSITORIES: ENA
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Project description:Hermansen2015 - denovo biosynthesis of pyrimidines in yeast
This model is described in the article:
Characterizing selective pressures on the pathway for de novo biosynthesis of pyrimidines in yeast.
Hermansen RA , Mannakee BK , Knecht W , Liberles DA , Gutenkunst RN
BMC Evolutionary Biology. 2015, 15:232
Abstract:
Selection on proteins is typically measured with the assumption that each protein acts independently. However, selection more likely acts at higher levels of biological organization, requiring an integrative view of protein function. Here, we built a kinetic model for de novo pyrimidine biosynthesis in the yeast Saccharomyces cerevisiae to relate pathway function to selective pressures on individual protein-encoding genes.Gene families across yeast were constructed for each member of the pathway and the ratio of nonsynonymous to synonymous nucleotide substitution rates (dN/dS) was estimated for each enzyme from S. cerevisiae and closely related species. We found a positive relationship between the influence that each enzyme has on pathway function and its selective constraint.We expect this trend to be locally present for enzymes that have pathway control, but over longer evolutionary timescales we expect that mutation-selection balance may change the enzymes that have pathway control.
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2024-09-02 | BIOMD0000000590 | BioModels
Project description:Sequencing of de novo lager yeast hybrids
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Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested. Three biological replicates of each of two species with one dye-flip each
2010-05-14 | E-GEOD-18909 | biostudies-arrayexpress
Project description:Proteome reallocation enables the selective de novo biosynthesis of non-linear, branched-chain acetate esters
2022-02-15 | MSV000088838 | MassIVE
Project description:Bakuchiol is a phenolic isoprenoid compound present in Babchi (Psoralea corylifolia Linn.) seeds. We examined the anti-influenza activity of synthetic bakuchiol using Madin-Darby canine kidney (MDCK) cells. We found that the naturally occurring form, (+)-(S)-bakuchiol, and its enantiomer, (-)-(R)-bakuchiol, inhibited influenza A infection and growth, and reduced the expression of viral mRNAs and proteins in MDCK cells. However, the molecular mechanism in anti-influenza activity of bakuchiol remains unclear. Thus, to evaluate its molecular mechanism in host cells, we performed the next generation sequencing analysis of the MDCK transcriptome in cells treated with bakuchiol and influenza A/PR/8/34. These results provide keys to elucidate the molecular mechnism of anti-influenza activity of bakuchiol for us, and these data will contribute to the development of novel approaches to anti-influenza treatments.
2015-10-06 | GSE73750 | GEO
Project description:The noncoding genome plays an important role in de novo gene birth and the emergence of genetic novelty. Nevertheless, how the properties of noncoding sequences could promote the birth of novel genes and shape the structural diversity and evolution of proteins remains unclear. Here, we investigated the potential of the noncoding genome of yeast to produce novel protein bricks that can give rise to novel genes or be integrated in pre-existing proteins, thus participating in protein structure evolution and diversity. Combining different bioinformatics approaches, we showed that intergenic ORFs of yeast encompass the large structural diversity of canonical proteins with the majority encoding peptides predicted as foldable. Then, we investigated the early stages of de novo gene birth with Ribosome Profiling and systematic reconstruction of yeast de novo gene ancestral sequences. We highlighted sequence and structural factors determining de novo gene birth and protein evolution. Finally, we showed a strong correlation between the fold potential of de novo genes and their ancestral ORFs reflecting the relationship between the noncoding genome and the protein structure universe.
2021-09-13 | GSE173861 | GEO
Project description:Dietary glucosamine can overcome defect in alpha/beta-T cell ontogeny caused by the loss of de novo hexosamine biosynthesis
2022-07-07 | MSV000089842 | MassIVE
Project description:Sequencing of adapted de novo lager yeast hybrids
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Project description:Pemetrexed is an anticancer agent that exerts its action by disrupting crucial folate-dependent metabolic processes essential for cell replication. In vitro studies have shown that pemetrexed behaves as a multitargeted antifolate by inhibiting thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are key folate-dependent enzymes for the de novo biosynthesis of thymidine and purine nucleotides.Pemetrexed is used as a standard therapeutic agent for lung cancer, pleural mesothelioma, peritoneal mesothelioma.In addition to these effective anti-cancer effect, Pemetrexed is not severe side effects of the medicine.
Pemetrexed has been research in colon cancer. Zhang, etc., demonstrated the anti-cancer effect of Pemetrexed in human colon cancer Cells.
Although sometimes made also two or more clinical studies, Pemetrexed was reported 15-17% of the treatment response rate in these two studies.
| 2201098 | ecrin-mdr-crc
Project description:Mycobacteria can synthesize NAD+ using either the de novo biosynthesis pathway or the salvage pathway. The deletion of the three genes involved specifically in the NAD+ de novo biosynthesis pathway in the human pathogen Mycobacterium tuberculosis had no effect on the growth of the strain in vivo. In contrast, the same deletion in the bovine pathogen Mycobacterium bovis resulted in a strain that could not grow in vivo and could only grow in vitro with substantial nicotinamide supplmentation. This striking difference was attributed to the known defect in the nicotinamidase PncA of M. bovis, since introducing the M. tuberculosis pncA gene into the M. bovis strain defective for de novo NAD+ biosynthesis restored growth in vitro and in vivo. This study demonstrates that NAD+ starvation is a cidal event in mycobacteria and confirms that enzymes common to the de novo and salvage pathways may be good drug targets. We also propose that simultaneously targeting both the salvage and the de novo NAD+ biosynthesis pathways represents a potentially effective way to treat infection with tubercle bacilli. To characterize the lethality induced by nicotinamide starvation transcriptional profiling of the auxotrophs was performed. Triplicate 50 mL cultures of M. tuberculosis and M. bovis Delta nadABC mutants were grown in 7H9 OADC glycerol 0.05% tween broth in 500 mL roller bottles to an OD600nm= 0.1 in a roller incubator at 37°C. The cells were washed 1x in PBS and resuspended in 50 mL 7H9 OADC glycerol 0.05% tween broth with or without 20mg/L nicotinamide and returned to the incubator. After 7 days, cultures were harvested.
2010-02-24 | GSE18909 | GEO