Yarrowia Lipolytica Sur2 Mutant for Sphingolipid Secretion
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Solution Overview
Problem
Current methods for mass-producing sphingolipids, such as dihydrosphingosine and glucosylceramide, are inefficient and costly due to low production levels in traditional yeast strains, and existing technologies struggle to produce these compounds on the cell surface without acetylation.
Innovation Solution
A Yarrowia lipolytica mutant strain with a deleted SUR2 gene is developed, allowing for the high-efficiency secretion and production of dihydrosphingosine, sphingosine, and glucosylceramide on the cell surface without additional acetylation, using genetic manipulation to enhance productivity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If traditional yeast strains are used for sphingolipid production, then the production process is simple, but the production level is low and extraction is costly
Solution Approach 1:
The patent extracts and removes the SUR2 gene (encoding dihydrosphingosine C4-hydroxylase) from the yeast genome through gene deletion. This eliminates the enzyme that converts dihydrosphingosine to phytosphingosine, causing dihydrosphingosine to accumulate and be secreted onto the cell surface, thereby simplifying extraction and increasing production level
Solution Approach 2:
The patent changes the metabolic parameter by deleting the SUR2 gene, which alters the sphingolipid biosynthesis pathway. This genetic modification causes a shift in metabolite distribution, resulting in high-level secretion of dihydrosphingosine and glucosylceramide onto the cell surface without requiring complex extraction procedures
2Productivity
If conventional methods are used, then the production process is straightforward, but acetylation is required and production efficiency is low
Solution Approach 1:
The patent removes the need for acetylation by deleting the SUR2 gene, which prevents the formation of phytosphingosine derivatives that would require acetylation. This directly enables the secretion of sphingoid-based precursors and sphingolipids without additional acetylation steps, improving both efficiency and manufacturing simplicity
Solution Approach 2:
Instead of using wild-type yeast that require acetylation to produce sphingolipids, the patent inverts the approach by creating a mutant strain that lacks the SUR2 gene. This inversion of the metabolic pathway allows direct secretion of dihydrosphingosine and glucosylceramide without the need for acetylation, reversing the conventional manufacturing requirement
Data Source
AI summary
The present invention relates to an oleaginous yeast Yarrowia lipolytica sur2 mutant strain and a method for producing and secreting, onto cell surfaces, sphingoid-based precursors, sphingosine and sphingolipids by using same. It has been identified that when a ceramidase gene is additionally introduced into a Ylsur2 deficient mutant strain, the secretion and production of dihydrosphingosine and sphingosine are increased and, further, it is has been identified that when a Ylsld1sur2 double mutant strain in which a SLD1 gene is additionally deficient in a Ylsur2 deficient mutant strain is prepared, growth recovery and sphingosine and human-type glucosylceramide secretion and production are increased.