&lt;i&gt;Saccharomyces cerevisiae&lt;/i&gt; lipid droplet associated enzyme Ypr147cp shows both TAG lipase and ester hydrolase activities

Kumar, Manoj; Thunuguntla, V B S C; Sekhar, B Chandra; Bondili, Jayakumar Singh

doi:10.2323/jgam.2017.08.001

Cited by 5 publications

(2 citation statements)

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“…For observation of lipid droplets by transmission electron microscopy, the sample of yeast was prepared according to previous literature [ 36 ]. For confocal microscopy, the lipid droplets staining and image acquisition were based on the method of Lv et al [ 37 ] with a slight modification.…”

Section: Methodsmentioning

confidence: 99%

Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved β-carotene production in Saccharomyces cerevisiae

Lin

Duan

et al. 2022

Microb Cell Fact

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Background The limitation of storage space, product cytotoxicity and the competition for precursor are the major challenges for efficiently overproducing carotenoid in engineered non-carotenogenic microorganisms. In this work, to improve β-carotene accumulation in Saccharomyces cerevisiae, a strategy that simultaneous increases cell storage capability and strengthens metabolic flux to carotenoid pathway was developed using exogenous oleic acid (OA) combined with metabolic engineering approaches. Results The direct separation of lipid droplets (LDs), quantitative analysis and genes disruption trial indicated that LDs are major storage locations of β-carotene in S. cerevisiae. However, due to the competition for precursor between β-carotene and LDs-triacylglycerol biosynthesis, enlarging storage space by engineering LDs related genes has minor promotion on β-carotene accumulation. Adding 2 mM OA significantly improved LDs-triacylglycerol metabolism and resulted in 36.4% increase in β-carotene content. The transcriptome analysis was adopted to mine OA-repressible promoters and IZH1 promoter was used to replace native ERG9 promoter to dynamically down-regulate ERG9 expression, which diverted the metabolic flux to β-carotene pathway and achieved additional 31.7% increase in β-carotene content without adversely affecting cell growth. By inducing an extra constitutive β-carotene synthesis pathway for further conversion precursor farnesol to β-carotene, the final strain produced 11.4 mg/g DCW and 142 mg/L of β-carotene, which is 107.3% and 49.5% increase respectively over the parent strain. Conclusions This strategy can be applied in the overproduction of other heterogeneous FPP-derived hydrophobic compounds with similar synthesis and storage mechanisms in S. cerevisiae. Graphical Abstract

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Section: Methodsmentioning

confidence: 99%

Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved β-carotene production in Saccharomyces cerevisiae

Lin

Duan

et al. 2022

Microb Cell Fact

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“…Saccharomyces cerevisiae's Ypr147cp, previously known as bifunctional enzyme which acts as triacylglycerol lipase and short chain ester hydrolase, null mutant results in the accumulation of both triacylglycerol and fatty acids derived from neutral lipids and phospholipids as well as an increase in the quantity of lipid droplets, contains an alpha/beta hydrolase domain with a conserved GXSXG lipase motif [ 1 ] localizes to lipid droplets [ 2 ]. GFP-fusion protein localizes to the cytoplasm [ 3 ] and is induced in response to the DNA-damaging agent MMS [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular modelling, docking and dynamics analysis of lipid droplet associated enzyme Ypr147cp from Saccharomyces cerevisiae

Sesham¹,

Manda²

2021

Bioinformation

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Ypr147cp of Saccharomyces cerevisiae was localized to lipid droplets. The recombinant Ypr147cp showed both triacylglycerol lipase and ester hydrolase activities. Knock out of YPR147C led to accumulation of TAG in ypr147cΔ when compared to wild type (WT). Transmission electron microscopic analysis of ypr147cΔ cells show increased lipid bodies. Moreover, the lipid profiling confirmed the accumulation of fatty acids derived from neutral and phospholipids in ypr147cΔ cells. Sequence analysis of Ypr147cp show the presence of an a/b hydrolase domain with the conserved GXSXG lipase motif. The YPR147c homology model was built and the modeled protein was analysed using RMSD and root mean square fluctuation (RMSF) for a 100 ns simulation trajectory. Docking the acetate, butyrate and palmitate ligands with the model confirmed covalent binding of ligands with the Ser207 of the GXSXG motif. Thus, Ypr147cp is a lipid droplet associated triacylglycerol lipase having short chain ester hydrolyzing capacity.

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Lipid droplet-associated hydrolase mobilizes stores of liver X receptor sterol ligands and protects against atherosclerosis

Goo,

Plakkal Ayyappan,

Cheeran

et al. 2024

Nat Commun

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Foam cells in atheroma are engorged with lipid droplets (LDs) that contain esters of regulatory lipids whose metabolism remains poorly understood. LD-associated hydrolase (LDAH) has a lipase structure and high affinity for LDs of foam cells. Using knockout and transgenic mice of both sexes, here we show that LDAH inhibits atherosclerosis development and promotes stable lesion architectures. Broad and targeted lipidomic analyzes of primary macrophages and comparative lipid profiling of atheroma identified a broad impact of LDAH on esterified sterols, including natural liver X receptor (LXR) sterol ligands. Transcriptomic analyzes coupled with rescue experiments show that LDAH modulates the expression of prototypical LXR targets and leads macrophages to a less inflammatory phenotype with a profibrotic gene signature. These studies underscore the role of LDs as reservoirs and metabolic hubs of bioactive lipids, and suggest that LDAH favorably modulates macrophage activation and protects against atherosclerosis via lipolytic mobilization of regulatory sterols.

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<i>Saccharomyces cerevisiae</i> lipid droplet associated enzyme Ypr147cp shows both TAG lipase and ester hydrolase activities

Cited by 5 publications

References 35 publications

Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved β-carotene production in Saccharomyces cerevisiae

Dual regulation of lipid droplet-triacylglycerol metabolism and ERG9 expression for improved β-carotene production in Saccharomyces cerevisiae

Molecular modelling, docking and dynamics analysis of lipid droplet associated enzyme Ypr147cp from Saccharomyces cerevisiae

Lipid droplet-associated hydrolase mobilizes stores of liver X receptor sterol ligands and protects against atherosclerosis

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