Characterization of a mutation that results in independence of oxidosqualene cyclase (Erg7) activity from the downstream 3-ketoreductase (Erg27) in the yeast ergosterol biosynthetic pathway

Layer, Jacob V.; Barnes, Brett M.; Yamasaki, Yuji; Barbuch, Robert J.; Li, Liangtao; Taramino, Silvia; Balliano, Gianni; Bard, Martin

doi:10.1016/j.bbalip.2012.09.012

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…Upon a block in mitochondrial respiration, Erg27 migrates rapidly from LPs to the ER, although this does not imply the relocation of Erg7 [ 4 ]. Interestingly, a fusion between Erg7 and the ER-resident protein Erg28 restores ergosterol biosynthesis to erg27 mutants, suggesting that the retention of Erg7 in the ER increases its activity [ 61 ]. Interestingly, Erg6 is mostly located in LPs [ 57 ], but can also be found in the ER, the cytoplasm and mitochondria.…”

Section: Regulation Of Ergosterol Biosynthesismentioning

confidence: 99%

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Jordá

Puig

2020

Genes

308

287

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Ergosterol is an essential component of fungal cell membranes that determines the fluidity, permeability and activity of membrane-associated proteins. Ergosterol biosynthesis is a complex and highly energy-consuming pathway that involves the participation of many enzymes. Deficiencies in sterol biosynthesis cause pleiotropic defects that limit cellular proliferation and adaptation to stress. Thereby, fungal ergosterol levels are tightly controlled by the bioavailability of particular metabolites (e.g., sterols, oxygen and iron) and environmental conditions. The regulation of ergosterol synthesis is achieved by overlapping mechanisms that include transcriptional expression, feedback inhibition of enzymes and changes in their subcellular localization. In the budding yeast Saccharomyces cerevisiae, the sterol regulatory element (SRE)-binding proteins Upc2 and Ecm22, the heme-binding protein Hap1 and the repressor factors Rox1 and Mot3 coordinate ergosterol biosynthesis (ERG) gene expression. Here, we summarize the sterol biosynthesis, transport and detoxification systems of S. cerevisiae, as well as its adaptive response to sterol depletion, low oxygen, hyperosmotic stress and iron deficiency. Because of the large number of ERG genes and the crosstalk between different environmental signals and pathways, many aspects of ergosterol regulation are still unknown. The study of sterol metabolism and its regulation is highly relevant due to its wide applications in antifungal treatments, as well as in food and pharmaceutical industries.

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Section: Regulation Of Ergosterol Biosynthesismentioning

confidence: 99%

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Jordá

Puig

2020

Genes

308

287

View full text Add to dashboard Cite

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“…The target compounds were predominantly detected as [M + Na] + using DCA. The metabolic pathway of sterols in fungi has been reported [4,6], and based on the previous research and elemental composition analysis of target ions by high-resolution FT ICR MS, sterols and their isomers were identified by accurate mass measurements. Since FT ICR MS is high-resolution, the exact m/z values of sterols can be measured accurately to determine their elemental compositions.…”

Section: Application To the Analysis Of Sterols In Yeast Cellsmentioning

confidence: 99%

“…For instance, sterols are the predominant components of the fungal cell membrane and inhibitors of the sterol biosynthetic pathway are potential antifungal therapeutic agents [3][4][5][6]. Metabolic profiling of fungal sterols is important for identification of antifungal drug targets and investigating mechanisms of drug resistance [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Coumarins as new matrices for matrix-assisted laser-desorption/ionization Fourier transform ion cyclotron resonance mass spectrometric analysis of hydrophobic compounds

Wang

Dai

Liu

et al. 2015

Analytica Chimica Acta

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“…Then, ERG13, HMG, ERG12, ERG8, ERG19, IDI1 and ERG20 successively catalyzed eight reactions to produce farnesyl pyrophosphate from acetoacetyl-CoA. The enzymes in the mevalonate pathway are essential genes which are conserved in eukaryotes [31][32][33]. The second part comprises 14 steps from farnesyl pyrophosphate to ergosterol (Fig.…”

Section: Ergosterol and Its Derivatives Are Mainly Obtained By The Mementioning

confidence: 99%

Combining transcriptomics and metabolomics to characterize ergosterol biosynthesis in Flammulina velutipes during the fruiting process

Wang

et al. 2019

Preprint

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Background: Flammulina velutipes (F. velutipes) is one of the most important mushrooms in Japan and China because of its potential medicinal and nutritional value. Ergosterol is an important precursor of vitamin D2, progesterone, hydrocortisone, brassinolide, and novel anticancer and anti-HIV drugs. One of the main methods for obtaining ergosterol is extraction of its natural products from fungi. However, because of the low production of ergosterol due to its inefficient biosynthesis, its approach cannot meet human needs. Therefore, increasing the ergosterol level in fungi is an important goal to be pursued. Although genes encoding key enzymes in the biosynthesis pathway of ergosterol have been identified in Saccharomyces cerevisiae, the mechanism and regulation of ergosterol biosynthesis in F. velutipes remain unclear, and are the focus of this study. Results: In this work, nine cDNA libraries produced from the three stages of F. velutipes were sequenced by using the Illumina HiSeqTM 4000 platform, resulting in at least 6.63 Gb of clean reads from each library. De novo sequence assemblers were used to generate 220,523 transcripts and 28,330 unigenes, which were annotated according to seven protein databases. Here, we combined transcriptomics and metabolomics approaches to investigate the biosynthesis of bioactive ergosterol from F. velutipes. The contents of 16 intermediates or metabolites from different stages (young fruiting body stage and mycelium stage) were found to be significantly different. Then, transcriptional profiling of the genes involved in ergosterol biosynthesis was carried out, and the transcripts of key genes involved in the metabolism were analysed. A total of 51 key unigenes (12 upregulated unigenes and 39 downregulated unigenes) were identified as differentially expressed. Furthermore, four genes (i.e., ERG10s, ERG1s, ERG11s and ERG26s) were identified as the most important genes that played roles in the regulation of the pathway flux towards ergosterol synthesis in F. velutipes. Combining transcriptomics and metabolomics, we explored the regulatory relationship between ergosterol biosynthesis genes and metabolites in F. velutipes. Conclusions: The data obtained in this work provide useful information for understanding the biosynthesis, metabolism and regulation of sterols in F. velutipes and for channelling the metabolic flux towards ergosterol at different growth stages.

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Characterization of a mutation that results in independence of oxidosqualene cyclase (Erg7) activity from the downstream 3-ketoreductase (Erg27) in the yeast ergosterol biosynthetic pathway

Cited by 11 publications

References 30 publications

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Coumarins as new matrices for matrix-assisted laser-desorption/ionization Fourier transform ion cyclotron resonance mass spectrometric analysis of hydrophobic compounds

Combining transcriptomics and metabolomics to characterize ergosterol biosynthesis in Flammulina velutipes during the fruiting process

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