Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae
Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this...
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Published in | Scientific reports Vol. 5; no. 1; p. 16319 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
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London
Nature Publishing Group UK
17.11.2015
Nature Publishing Group |
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Abstract | Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast
Saccharomyces cerevisiae
by eliminating the genes for yeast sphingolipid hydroxylases (encoded by
SUR2
and
SCS7
) and introducing the gene for a human sphingolipid desaturase (encoded by
DES1
). The inactivation of the ceramidase gene
YDC1
, overexpression of the inositol phosphosphingolipid phospholipase C gene
ISC1
and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids. |
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AbstractList | Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7) and introducing the gene for a human sphingolipid desaturase (encoded by DES1). The inactivation of the ceramidase gene YDC1, overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1, and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids. Abstract Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7 ) and introducing the gene for a human sphingolipid desaturase (encoded by DES1 ). The inactivation of the ceramidase gene YDC1 , overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1 and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids. Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7 ) and introducing the gene for a human sphingolipid desaturase (encoded by DES1 ). The inactivation of the ceramidase gene YDC1 , overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1 and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids. Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks involved with using products of animal origin and the low productivity of plants, the availability of ceramides is currently limited. In this study, we successfully developed a system that produces sphingosine-containing human ceramide-NS in the yeast Saccharomyces cerevisiae by eliminating the genes for yeast sphingolipid hydroxylases (encoded by SUR2 and SCS7 ) and introducing the gene for a human sphingolipid desaturase (encoded by DES1 ). The inactivation of the ceramidase gene YDC1 , overexpression of the inositol phosphosphingolipid phospholipase C gene ISC1 , and endoplasmic reticulum localization of the DES1 gene product resulted in enhanced production of ceramide-NS. The engineered yeast strains can serve as hosts not only for providing a sustainable source of ceramide-NS but also for developing further systems to produce sphingosine-containing sphingolipids. |
ArticleNumber | 16319 |
Author | Okuhara, Hiroaki Tojo, Hiromasa Kodama, Yukiko Funato, Kouichi Nagano, Hideaki Hatanaka, Haruyo Tsuruno, Masahiro Murakami, Suguru Shimamoto, Toshi |
Author_xml | – sequence: 1 givenname: Suguru surname: Murakami fullname: Murakami, Suguru organization: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University – sequence: 2 givenname: Toshi surname: Shimamoto fullname: Shimamoto, Toshi organization: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University – sequence: 3 givenname: Hideaki surname: Nagano fullname: Nagano, Hideaki organization: Suntory World Research Center – sequence: 4 givenname: Masahiro surname: Tsuruno fullname: Tsuruno, Masahiro organization: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University – sequence: 5 givenname: Hiroaki surname: Okuhara fullname: Okuhara, Hiroaki organization: Suntory World Research Center – sequence: 6 givenname: Haruyo surname: Hatanaka fullname: Hatanaka, Haruyo organization: Suntory World Research Center – sequence: 7 givenname: Hiromasa surname: Tojo fullname: Tojo, Hiromasa organization: Department of Biophysics and Biochemistry, Osaka University Graduate School of Medicine – sequence: 8 givenname: Yukiko surname: Kodama fullname: Kodama, Yukiko organization: Suntory World Research Center – sequence: 9 givenname: Kouichi surname: Funato fullname: Funato, Kouichi organization: Department of Biofunctional Science and Technology, Graduate School of Biosphere Science, Hiroshima University |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26573460$$D View this record in MEDLINE/PubMed |
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Snippet | Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of the risks... Abstract Ceramide is one of the most important intercellular components responsible for the barrier and moisture retention functions of the skin. Because of... |
SourceID | pubmedcentral proquest crossref pubmed springer |
SourceType | Open Access Repository Aggregation Database Index Database Publisher |
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SubjectTerms | 101/58 45/29 631/326/2522 631/61/318 82/16 Amidohydrolases - genetics Amidohydrolases - metabolism Amino Acid Sequence Antifungal Agents - pharmacology C gene Ceramidase Ceramide Ceramides - analysis Ceramides - metabolism Chromatography, High Pressure Liquid Depsipeptides - pharmacology Desaturase Endoplasmic reticulum Endoplasmic Reticulum - metabolism Humanities and Social Sciences Humans Industrial Microbiology - methods Inositol Localization Metabolic Engineering Microscopy, Fluorescence Mixed Function Oxygenases - deficiency Mixed Function Oxygenases - genetics multidisciplinary Oxidoreductases - genetics Oxidoreductases - metabolism Phospholipase C Saccharomyces cerevisiae - drug effects Saccharomyces cerevisiae - metabolism Saccharomyces cerevisiae Proteins - genetics Saccharomyces cerevisiae Proteins - metabolism Science Skin Sphingolipids Sphingosine - analysis Sphingosine - metabolism Tandem Mass Spectrometry Type C Phospholipases - genetics Type C Phospholipases - metabolism Yeast |
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Title | Producing human ceramide-NS by metabolic engineering using yeast Saccharomyces cerevisiae |
URI | https://link.springer.com/article/10.1038/srep16319 https://www.ncbi.nlm.nih.gov/pubmed/26573460 https://www.proquest.com/docview/1899817757 https://search.proquest.com/docview/1735900559 https://pubmed.ncbi.nlm.nih.gov/PMC4647206 |
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