Wednesday, August 1, 2007 - 11:00 AM
S152
Engineering sphingolipid biosynthesis in non-conventional yeasts
Daniel Börgel1, Thomas Hüller2, Tim Köhler2, and Steffen Schaffer2. (1) Institute for Molecular Biosciences, Johann Wolfgang Goethe-University Frankfurt/Main, Max-von-Laue-Str. 9, Frankfurt/Main, 60438, Germany, (2) Creavis Technologies and Innovation, Degussa GmbH, Paul-Baumann-Str. 1, Bldg. 1420/PB 18, Marl, 45764, Germany
Sphingolipids are important signalling molecules in eukaryotic cells. Moreover, they serve important structural functions as constituents of lipid bilayers and the permeability barrier of mammalian skin. Ceramides, a specific group of sphingolipids containing sphingosine, phytosphingosine or 6-hydroxysphingosine as sphingoid base in amide linkage with a fatty acid, are the main lipid components of the protective upper skin layer. Consequently, they are of commercial interest as active ingredients for the cosmetic industry. Topical application of ceramide-containing cosmetic formulations has been shown to significantly improve barrier function in human skin.
The yeast Pichia ciferrii has been known for many years to secrete large amounts of acetylated phytosphingosine, and is already employed for biotechnological production of this compound on industrial scale. In contrast, no such process currently exists for production of sphingosine. As sphingosine and phytosphingosine are derived from the same precursor molecule (dihydrosphingosine), we attempted to redirect sphingoid base production from phytosphingosine to sphingosine by metabolic engineering in Pichia ciferrii.
Development of genetic tools for this non-conventional yeast as well as metabolic engineering work to achieve efficient conversion of dihydrosphingosine into sphingosine will be presented.
The yeast Pichia ciferrii has been known for many years to secrete large amounts of acetylated phytosphingosine, and is already employed for biotechnological production of this compound on industrial scale. In contrast, no such process currently exists for production of sphingosine. As sphingosine and phytosphingosine are derived from the same precursor molecule (dihydrosphingosine), we attempted to redirect sphingoid base production from phytosphingosine to sphingosine by metabolic engineering in Pichia ciferrii.
Development of genetic tools for this non-conventional yeast as well as metabolic engineering work to achieve efficient conversion of dihydrosphingosine into sphingosine will be presented.