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

Ferreira, Raphael; Teixeira, Paulo Gonçalves; Siewers, Verena; Nielsen, Jens

doi:10.1073/pnas.1715282115

Cited by 55 publications

(48 citation statements)

References 40 publications

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“…As shown in Fig. 3, when cultivated in minimal medium with 20 g/L glucose, ZS01 accumulated 497.9 mg/L FFAs at 72 h with a high productivity of 133.7 mg/L/OD, which was consistent with previous studies [8,9]. After 72 h, ZS01 accumulated more FFAs since there was ethanol remaining and the FFA titer reached 734.2 mg/L at 144 h when ethanol was exhausted ( Fig.…”

Section: Resultssupporting

confidence: 89%

Expressing a Cytosolic Pyruvate Dehydrogenase Complex to Increase Free Fatty Acid Production in Saccharomyces Cerevisiae

Zhang

Qin

et al. 2020

Preprint

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Background Saccharomyces cerevisiae is being exploited as a cell factory to produce fatty acids and their derivatives as biofuels. Previous studies found that both precursor supply and fatty acid metabolism deregulation are essential for enhanced fatty acid synthesis. A bacterial pyruvate dehydrogenase (PDH) complex expressed in the yeast cytosol was reported to enable production of cytosolic acetyl-CoA with lower energy cost and no toxic intermediate. Results Overexpression of the PDH complex significantly increased cell growth, ethanol consumption and reduced glycerol accumulation. Furthermore, to optimize the redox imbalance in production of fatty acids from glucose, two endogenous NAD+-dependent glycerol-3-phosphate dehydrogenases were deleted, and a heterologous NADP+-dependent glyceraldehyde-3-phosphate dehydrogenase was introduced. The final strain with engineering of precursor and co-factor metabolism could produce 840.5 mg/L free fatty acid in shake flask, which was 83.2% higher than the control strain. Profile analysis of free fatty acid suggested the cytosolic PDH complex mainly resulted in the increases of unsaturated fatty acids (C16:1 and C18:1). Conclusions We demonstrated that cytosolic PDH pathway enabled more efficient acetyl-CoA provision with the lower ATP cost, and improved FFA production. Together with engineering of the redox factor rebalance, the cytosolic PDH pathway could achieve high level of FFA production at similar levels of other best acetyl-CoA producing pathways.

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Section: Resultssupporting

confidence: 89%

Expressing a Cytosolic Pyruvate Dehydrogenase Complex to Increase Free Fatty Acid Production in Saccharomyces Cerevisiae

Zhang

Qin

et al. 2020

Preprint

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Section: Discussionmentioning

confidence: 97%

“…To date, few studies have explored the hydrolysis of phospholipids in arbuscules. In yeast, however, phospholipase B of fungal origin is the key player in phospholipid hydrolysis (Ferreira et al, 2018). More recently, Li et al (2019) proposed that a purple acid phosphatase of soybean origin participated in the hydrolysis of phospholipids in arbuscule membranes during arbuscule degeneration.…”

Section: Low Ph Regulates the Dynamics Of Lipid Accumulation In Degenmentioning

confidence: 99%

Linking lipid transfer with reduced arbuscule formation in tomato roots colonized by arbuscular mycorrhizal fungus under low pH stress

Zhang

Feng

Zhu

et al. 2019

Environmental Microbiology

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Summary Arbuscules are the core structures of arbuscular mycorrhizae (AM), and arbuscule development is regulated by environmental stress, e.g., low pH. Recent studies indicate that lipid transfer from plants is essential for AM fungal colonization; however, the role of lipid transfer in arbuscule formation and the dynamics of lipid accumulation in arbuscules under low pH stress are far from well understood. In the symbiosis of tomato and Rhizophagus intraradices under contrasting pH conditions (pH 4.5 vs. pH 6.5), we investigated arbuscule formation, nutrient uptake, alkaline phosphatase activity and lipid accumulation; examined the gene expression involved in phosphate transport, lipid biosynthesis and transfer and sugar metabolism; and visualized the lipid dynamics in arbuscules. Low pH greatly inhibited arbuscule formation, in parallel with reduced phospholipid fatty acids accumulation in AM fungus and decreased P uptake. This reduction was supported by the decreased expression of plant genes encoding lipid biosynthesis and transfer. More degenerating arbuscules were observed under low pH conditions, and neutral lipid fatty acids accumulated only in degenerating arbuscules. These data reveal that, under low pH stress, reduced lipid transfer from hosts to AM fungi is responsible for the inhibited arbuscule formation.

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“…Fatty acids are one of the main components of yeast cell membranes 31 and play important roles in cell membrane fluid and membrane permeability. 32 Aspirin was reported to interfere with the function of cell membrane by altering membrane fluidity. 6 To assess the impact of aspirin on cell membrane integrity, PI was used as a fluorescent dye.…”

Section: Aspirin Causes Membrane Damage In Yeastmentioning

confidence: 99%

Aspirin Causes Lipid Accumulation and Damage to Cell Membrane by Regulating DCI1/OLE1 in Saccharomyces cerevisiae

Zhu

Yan

et al. 2020

Microbial Drug Resistance

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Aspirin is one of the most commonly used nonsteroidal anti-inflammatory drugs. Various potential pharmacological effects of aspirin, such as anticancer, antibacterial activity, and prolonging life expectancy have been discovered. However, the mechanism of aspirin is not fully elucidated. Herein, the effects of aspirin on fatty acid metabolism in yeast cell model Saccharomyces cerevisiae were studied. The results showed that aspirin can induce lipid accumulation and reduce the unsaturated fat index in cells. The assessment of cell membrane integrity demonstrated that aspirin caused damage to the cell membrane. These effects of aspirin were attributed to the alterations of the expression of DCI1 and OLE1. Similarly, aspirin was able to cause lipid accumulation and damage to the cell membrane by interfering with the expression of OLE1 in Candida albicans. These findings are expected to improve current understanding of the mode of action of aspirin and provide a novel strategy for antifungal drug design.

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

Cited by 55 publications

References 40 publications

Expressing a Cytosolic Pyruvate Dehydrogenase Complex to Increase Free Fatty Acid Production in Saccharomyces Cerevisiae

Expressing a Cytosolic Pyruvate Dehydrogenase Complex to Increase Free Fatty Acid Production in Saccharomyces Cerevisiae

Linking lipid transfer with reduced arbuscule formation in tomato roots colonized by arbuscular mycorrhizal fungus under low pH stress

Aspirin Causes Lipid Accumulation and Damage to Cell Membrane by Regulating DCI1/OLE1 in Saccharomyces cerevisiae

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