Yarrowia lipolytica sur2 mutant strain and method for cell-surface secretion and production of sphingoid-based precursors, sphingosine, and sphingolipids using the same

Cell-surface secretion and production of sphingoid bases using SUR2-deficient Yarrowia yeast

This technology utilizes a mutant strain of the oleaginous yeast Yarrowia lipolytica, in which the dihydrosphingosine C4-hydroxylase gene (SUR2) is deleted, to secrete and produce dihydrosphingosine and glucosylceramide on the cell surface. It also includes recombinant strains that produce sphingosine and human-type glucosylceramide through the introduction of a ceramidase gene or the additional deletion of the SLD1 gene.

Ceramides and sphingoid bases are widely used in cosmetics for skin barrier reinforcement, moisturizing, and anti-inflammatory properties, but efficient biological mass production has been challenging. Existing yeast production systems have limitations, such as the need for an acetylation process and complex extraction procedures for intracellularly accumulated products.

This technology uses a GRAS-certified Yarrowia lipolytica mutant strain cultured in a glycerol-based medium to secrete products onto the cell surface via lipid droplets without the need for separate acetylation. This significantly increases dihydrosphingosine productivity and simplifies the extraction process. Applicable to the bio-manufacturing of cosmetic ceramide ingredients and functional lipid materials, it serves as a production platform for the low-cost supply of human-type sphingolipids.

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Key Features:

• Yarrowia lipolytica mutant strain with enhanced cell-surface secretion and production of dihydrosphingosine or glucosylceramide due to deletion or suppressed expression of the SUR2 gene
• A step of culturing the mutant strain in a medium containing glycerol as a carbon source to secrete products onto the cell surface via lipid droplets without acetylation
• Recombinant strain with enhanced sphingosine secretion and production, achieved by introducing a gene encoding human or yeast-derived ceramidase into the mutant strain
• Recombinant strain with enhanced human-type glucosylceramide secretion and production, achieved by the additional deletion of the SLD1 gene encoding Δ8-desaturase in the mutant strain

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This invention was developed with support from the Center for Microbial Survival Systems of the Ministry of Science and ICT.

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