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Engineering lipid droplet assembly mechanisms for improved triacylglycerols accumulation in Saccharomyces cerevisiae.

08:00 EDT 11th June 2018 | BioPortfolio

Summary of "Engineering lipid droplet assembly mechanisms for improved triacylglycerols accumulation in Saccharomyces cerevisiae."

Production of triacylglycerols (TAGs) through microbial fermentation is an emerging alternative to plant and animal-derived sources. The yeast Saccharomyces cerevisiae is a preferred organism for industrial use but has natively a very poor capacity of TAG production and storage. Here, we engineered S. cerevisiae for accumulation of high TAG levels through the use of structural and physiological factors that influence assembly and biogenesis of lipid droplets. First, human and fungal perilipin genes were expressed, increasing TAG content by up to 36% when expressing the human perilipin gene PLIN3. Secondly, expression of the FIT2 homologue YFT2 resulted in a 26% increase in TAG content. Lastly, the genes ERD1 and PMR1 were deleted in order to induce an ER stress response and stimulate lipid droplet formation, increasing TAG content by 72% for Δerd1. These new approaches were implemented in previously engineered strains that carry high flux of fatty acid biosynthesis and conversion of acyl-CoA into TAG, resulting in improvements of up to 138% over those high-producing strains without any substantial growth effects or abnormal cell morphology. We find that these approaches not only represent a significant improvement of S. cerevisiae for TAG production, but also highlight the importance of lipid droplet dynamics for high lipid accumulation in yeast.

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This article was published in the following journal.

Name: FEMS yeast research
ISSN: 1567-1364
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A family of vertebrate and insect lipid droplet associated proteins. They consist of a conserved N-terminal PAT domain (an alpha-helical region of about 110 amino acids), an 11-mer repeat region, and lipid-binding hydrophobic regions or 4-helix bundles near their C-termini. Perilipins transiently or constitutively localize to LIPID DROPLETS in ADIPOCYTES and FOAM CELLS, especially in regions adjacent to the PLASMA MEMBRANE and ENDOPLASMIC RECTICULUM. They are critical for lipid droplet synthesis and homeostasis as well as the regulation of lipid metabolism. Genetic variations in perilipins are associated with ATHEROSCLEROSIS; OBESITY; and DIABETES MELLITUS.

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