scholarly journals Multi-Omics Analysis of Lipid Metabolism for a Marine Probiotic Meyerozyma guilliermondii GXDK6 Under High NaCl Stress

2022 ◽  
Vol 12 ◽  
Author(s):  
Huijie Sun ◽  
Xinghua Cai ◽  
Bing Yan ◽  
Huashan Bai ◽  
Duotao Meng ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Drug Target ◽  
Nacl Stress ◽  
Intracellular Accumulation ◽  
Meyerozyma Guilliermondii ◽  
New Methods ◽  
Cell Factories ◽  
Exogenous Addition ◽  
Dependent Signal ◽  
Integrated Omics

Investigating microbial lipid regulation contributes to understanding the lipid-dependent signal transduction process of cells and helps to improve the sensitivity of microorganisms to environmental factors by interfering with lipid metabolism, thus beneficial for constructing advanced cell factories of novel molecular drugs. Integrated omics technology was used to systematically reveal the lipid metabolism mechanism of a marine Meyerozyma guilliermondii GXDK6 under high NaCl stress and test the sensitivity of GXDK6 to antibiotics when its lipid metabolism transformed. The omics data showed that when GXDK6 perceived 10% NaCl stress, the expression of AYR1 and NADPH-dependent 1-acyldihydroxyacetone phosphate reductase was inhibited, which weaken the budding and proliferation of cell membranes. This finding was further validated by decreased 64.39% of OD600 under 10% NaCl stress when compared with salt-free stress. In addition, salt stress promoted a large intracellular accumulation of glycerol, which was also verified by exogenous addition of glycerol. Moreover, NaCl stress remarkably inhibited the expression of drug target proteins (such as lanosterol 14-alpha demethylase), thereby increasing sensitivity to fluconazole. This study provided new insights into the molecular mechanism involved in the regulation of lipid metabolism in Meyerozyma guilliermondii strain and contributed to developing new methods to improve the effectiveness of killing fungi with lower antibiotics.

scholarly journals Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion

2018 ◽  
Vol 115 (6) ◽  
pp. 1262-1267 ◽  
Author(s):  
Raphael Ferreira ◽  
Paulo Gonçalves Teixeira ◽  
Verena Siewers ◽  
Jens Nielsen
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Metabolic Network ◽  
Feedback Regulation ◽  
Acid Activation ◽  
Phospholipid Hydrolysis ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
High Level

Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid activation genes (the first step in β-oxidation), main storage lipid formation genes, and phosphatidate phosphatase genes resulted in a constrained lipid metabolic network in which fatty acid flux was directed to a large extent toward phospholipids. This resulted in simultaneous increases of phospholipids by up to 2.8-fold and of FFAs by up to 40-fold compared with wild-type levels. Further deletion of phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and 105% increase in phospholipid levels, suggesting that phospholipid hydrolysis plays an important role in FFA production when phospholipid levels are increased. The multiple deletion mutant generated allowed for a study of fatty acid dynamics in lipid metabolism and represents a platform strain with interesting properties that provide insight into the future development of lipid-related cell factories.

scholarly journals Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism

2016 ◽  
Vol 19 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Jennifer Tisoncik-Go ◽  
David J. Gasper ◽  
Jennifer E. Kyle ◽  
Amie J. Eisfeld ◽  
Christian Selinger ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Lipid Metabolism ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
Host Responses ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Pandemic H1n1 Influenza ◽  
Integrated Omics

scholarly journals Preventing type 2 diabetes and cardiovascular disease in metabolic syndrome: the role of PPARα

2007 ◽  
Vol 4 (3_suppl) ◽  
pp. S12-S14 ◽  
Author(s):  
Jorge Plutzky
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Drug Target ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Central Target ◽  
The Metabolic Syndrome

The clustering of cardiovascular risk factors associated with the metabolic syndrome and type 2 diabetes suggests central mechanisms may exist that account for the presence of these abnormalities. Likewise, this clustering also suggests that key therapeutic targets may exist that could allow improvements in many of these parameters. Extensive data implicate peroxisome proliferator-activated receptor-alpha (PPARα) as an important transcriptional regulator of lipid metabolism, energy balance and inflammation. PPARα is also an established drug target. Experimental data show that activation of PPARα by agonists such as fenofibrate improves dyslipidaemia, increases cholesterol efflux and limits inflammation. All of these effects would also be predicted to decrease atherosclerotic risk. Evidence from surrogate markers in humans is also supportive of the concept that PPARα may act as a central target capable of influencing a variety of different pathways involved in lipid metabolism. Thus, fenofibrate offers the potential for inducing a co-ordinated PPARα response that may improve dyslipidaemia, repress inflammation and limit atherosclerosis in patients with the metabolic syndrome or type 2 diabetes.

scholarly journals Patatin-Related Phospholipase pPLAIIIγ Involved in Osmotic and Salt Tolerance in Arabidopsis

Plants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 650
Author(s):  
Jianwu Li ◽  
Maoyin Li ◽  
Shuaibing Yao ◽  
Guangqin Cai ◽  
Xuemin Wang
Keyword(s):  
Signal Transduction ◽  
Fatty Acids ◽  
Abiotic Stress ◽  
Lipid Metabolism ◽  
Salt Tolerance ◽  
Stress Responses ◽  
Nacl Stress ◽  
Plant Tolerance ◽  
Wild Type ◽  
Hydrolyzing Enzymes

Patatin-related phospholipases (pPLAs) are acyl-hydrolyzing enzymes implicated in various processes, including lipid metabolism, signal transduction, plant growth and stress responses, but the function for many specific pPLAs in plants remains unknown. Here we determine the effect of patatin-related phospholipase A pPLAIIIγ on Arabidopsis response to abiotic stress. Knockout of pPLAIIIγ rendered plants more sensitive whereas overexpression of pPLAIIIγ enhanced plant tolerance to NaCl and drought in seed germination and seedling growth. The pPLAIIIγ-knockout and overexpressing seedlings displayed a lower and higher level of lysolipids and free fatty acids than that of wild-type plants in response to NaCl stress, respectively. These results indicate that pPLAIIIγ acts a positive regulator of salt and osmatic stress tolerance in Arabidopsis.

scholarly journals Leucine Biosynthesis Is Involved in Regulating High Lipid Accumulation in Yarrowia lipolytica

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Eduard J. Kerkhoven ◽  
Young-Mo Kim ◽  
Siwei Wei ◽  
Carrie D. Nicora ◽  
Thomas L. Fillmore ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Lipid Metabolism ◽  
Yarrowia Lipolytica ◽  
Lipid Accumulation ◽  
Carbon Limitation ◽  
Leucine Biosynthesis ◽  
Protein Levels ◽  
Microbial Cell Factories ◽  
Cell Factories ◽  
High Level

ABSTRACT The yeast Yarrowia lipolytica is a potent accumulator of lipids, and lipogenesis in this organism can be influenced by a variety of factors, such as genetics and environmental conditions. Using a multifactorial study, we elucidated the effects of both genetic and environmental factors on regulation of lipogenesis in Y. lipolytica and identified how two opposite regulatory states both result in lipid accumulation. This study involved comparison of a strain overexpressing diacylglycerol acyltransferase ( DGA1 ) with a control strain grown under either nitrogen or carbon limitation conditions. A strong correlation was observed between the responses on the transcript and protein levels. Combination of DGA1 overexpression with nitrogen limitation resulted in a high level of lipid accumulation accompanied by downregulation of several amino acid biosynthetic pathways, including that of leucine in particular, and these changes were further correlated with a decrease in metabolic fluxes. This downregulation was supported by the measured decrease in the level of 2-isopropylmalate, an intermediate of leucine biosynthesis. Combining the multi-omics data with putative transcription factor binding motifs uncovered a contradictory role for TORC1 in controlling lipid accumulation, likely mediated through 2-isopropylmalate and a Leu3-like transcription factor. IMPORTANCE The ubiquitous metabolism of lipids involves refined regulation, and an enriched understanding of this regulation would have wide implications. Various factors can influence lipid metabolism, including the environment and genetics. We demonstrated, using a multi-omics and multifactorial experimental setup, that multiple factors affect lipid accumulation in the yeast Yarrowia lipolytica . Using integrative analysis, we identified novel interactions between nutrient restriction and genetic factors involving regulators that are highly conserved among eukaryotes. Given that lipid metabolism is involved in many diseases but is also vital to the development of microbial cell factories that can provide us with sustainable fuels and oleochemicals, we envision that our report introduces foundational work to further unravel the regulation of lipid accumulation in eukaryal cells.

scholarly journals Copper Tolerance Mechanism of the Novel Marine Multi-Stress Tolerant Yeast Meyerozyma guilliermondii GXDK6 as Revealed by Integrated Omics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Ru Bu ◽  
Bing Yan ◽  
Huijie Sun ◽  
Mengcheng Zhou ◽  
Huashan Bai ◽  
...  
Keyword(s):  
High Stress ◽  
Copper Tolerance ◽  
Copper Stress ◽  
Glutathione Metabolism ◽  
Transferase Activity ◽  
Tolerance Mechanism ◽  
Whole Genome Analysis ◽  
Meyerozyma Guilliermondii ◽  
Integrated Omics ◽  
Species Production

Various agricultural products used in food fermentation are polluted by heavy metals, especially copper, which seriously endangers human health. Methods to remove copper with microbial strategies have gained interests. A novel Meyerozyma guilliermondii GXDK6 could survive independently under high stress of copper (1400 ppm). The copper tolerance mechanism of GXDK6 was revealed by integrated omics in this work. Whole-genome analysis showed that nine genes (i.e., CCC2, CTR3, FRE2, GGT, GST, CAT, SOD2, PXMP4, and HSP82) were related to GXDK6 copper tolerance. Copper stress elevated glutathione metabolism-related gene expression, glutathione content, and glutathione sulfur transferase activity, suggesting enhanced copper conjugation and detoxification in cells. The inhibited copper uptake by Ctr3 and enhanced copper efflux by Ccc2 contributed to the decrease in intracellular copper concentration. The improved expression of antioxidant enzyme genes (PXMP4, SOD2, and CAT), accompanied by the enhanced activities of antioxidant enzymes (peroxidase, superoxide dismutase, and catalase), decreased copper-induced reactive oxygen species production, protein carbonylation, lipid peroxidation, and cell death. The metabolite D-mannose against harsh stress conditions was beneficial to improving copper tolerance. This study contributed to understanding the copper tolerance mechanism of M. guilliermondii and its application in removing copper during fermentation.

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