Ergosterol Turnover in Yeast: An Interplay between Biosynthesis and Transport

Sokolov, Svyatoslav S.; Trushina, Nataliya I.; Severin, Fedor F.; Knorre, Dmitry A.

doi:10.1134/s0006297919040023

Cited by 39 publications

(29 citation statements)

References 99 publications

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“…For instance, the erg6 mutant accumulates its substrate and several sterols resulting from the catalytic activity of Erg2, Erg3 and Erg5 on zymosterol [17]. These erg mutants are defective in different cellular processes and show alterations in the resistance to certain stresses (reviewed in [16,18]). The deletion of one of the two isozymes encoded by HMGR (HMG1 or HMG2) has only a little effect on cell growth, but the double mutant is inviable.…”

Section: Ergosterol Biosynthesis In S Cerevisiaementioning

confidence: 99%

“…Due to their hydrophobicity, sterols are transported inside cells either in a vesicular manner or via lipid binding/transfer proteins. The last mechanism seems to be the prevailing one in S. cerevisiae, since the inhibition of vesicular transport through the secretory pathway does not significantly affect sterol transport to the PM (reviewed in [18]). In S. cerevisiae, sterol uptake initiates with the interaction between the external sterol and the cell wall, followed by its incorporation into the PM in an ATP-dependent manner by the PM ATP-binding cassette (ABC) transporters Aus1 and Pdr11 [31].…”

Section: Sterol Acquisition and Transport In S Cerevisiaementioning

confidence: 99%

“…To prevent these harmful effects, yeast cells utilize multiple detoxification mechanisms. Sterols cannot be degraded, but are either stored in the form of steryl esters (SE) in LPs or secreted into the medium as sterol acetates (reviewed in [6,18]). Under aerobic conditions, SE formation in the ER is catalyzed mainly by Are2, which has a significant preference for ergosterol as a substrate, whereas Are1 performs this function in hypoxia [44].…”

Section: Sterol Detoxificationmentioning

confidence: 99%

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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: Ergosterol Biosynthesis In S Cerevisiaementioning

confidence: 99%

Section: Sterol Acquisition and Transport In S Cerevisiaementioning

confidence: 99%

Section: Sterol Detoxificationmentioning

confidence: 99%

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Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Jordá

Puig

2020

Genes

308

287

View full text Add to dashboard Cite

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“…Ergosterol, similar to cholesterol in animals and phytosterols in plants, is the most abundant sterol in fungi and plays an essential role in maintaining physicochemical properties of plasma membrane and involves in protein sorting and protein receptor regulation [21]. The biosynthesis of ergosterol exists in almost all yeast species and is well characterized, especially in the model organism Saccharomyces cerevisiae.…”

Section: Ergosterol Biosynthesis In Yeastmentioning

confidence: 99%

Yeast as a promising heterologous host for steroid bioproduction

2020

Journal of Industrial Microbiology and Biotechnology

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With the rapid development of synthetic biology and metabolic engineering technologies, yeast has been generally considered as promising hosts for the bioproduction of secondary metabolites. Sterols are essential components of cell membrane, and are the precursors for the biosynthesis of steroid hormones, signaling molecules, and defense molecules in the higher eukaryotes, which are of pharmaceutical and agricultural significance. In this mini-review, we summarize the recent engineering efforts of using yeast to synthesize various steroids, and discuss the structural diversity that the current steroidproducing yeast can achieve, the challenge and the potential of using yeast as the bioproduction platform of various steroids from higher eukaryotes.

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“…Ergosterol biosynthesis takes place in the endoplasmic reticulum (ER). Ergosterol is subsequently transported to the plasma membrane (PM), by (mostly) non-vesicular mechanisms (Baumann et al, 2005;Alli-Balogun and Levine, 2019;Sokolov et al, 2019). Lam proteins with sterol-binding StART-like domains contribute to ER/PM ergosterol turnover (Gatta et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles

et al. 2020

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Lam proteins transport sterols between the membranes of different cellular compartments. In Saccharomyces cerevisiae, the LAM gene family consists of three pairs of paralogs. Because the function of paralogous genes can be redundant, the phenotypes of only a small number of LAM gene deletions have been reported; thus, the role of these genes in yeast physiology is still unclear. Here, we surveyed the phenotypes of double and quadruple deletants of paralogous LAM2(YSP2)/LAM4 and LAM1(YSP1)/LAM3(SIP3) genes that encode proteins localized in the junctions of the plasma membrane and endoplasmic reticulum. The quadruple deletant showed increased sterol content and a strong decrease in ethanol, heat shock and high osmolarity resistance. Surprisingly, the quadruple deletant and LAM2/LAM4 double deletion strain showed increased tolerance to the azole antifungals clotrimazole and miconazole. This effect was not associated with an increased rate of ABC-transporter substrate efflux. Possibly, increased sterol pool in the LAM deletion strains postpones the effect of azoles on cell growth. Alternatively, LAM deletions might alleviate the toxic effect of sterols as Lam proteins can transport toxic sterol biosynthesis intermediates into membrane compartments that are sensitive to these compounds. Our findings reveal novel biological roles of LAM genes in stress tolerance and suggest that mutations in these genes may confer upregulation of a mechanism that provides resistance to azole antifungals in pathogenic fungi.

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Ergosterol Turnover in Yeast: An Interplay between Biosynthesis and Transport

Cited by 39 publications

References 99 publications

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae

Yeast as a promising heterologous host for steroid bioproduction

LAM Genes Contribute to Environmental Stress Tolerance but Sensibilize Yeast Cells to Azoles

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