ArticleThe Journal of biological chemistry2011
Two pathways of sphingolipid biosynthesis are separated in the yeast Pichia pastoris.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 62 citations in OpenAlex.
- Ceramides: A Biologically Attractive Lipid and Advances in Acquisition Strategies.Antioxidants (Basel, Switzerland) · 2026Review
- Fungal Sphingolipids: Biosynthesis Pathways, Structural Features and Biological Functions.Journal of fungi (Basel, Switzerland) · 2026Review
- The antimicrobial activity of ETD151 defensin is dictated by the presence of glycosphingolipids in the targeted organisms.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Genetic Characterization of the Acidic and Neutral Glycosphingolipid Biosynthetic Pathways inMicroorganisms · 2023Article
- Diversity in sphingolipid metabolism across land plants.Journal of experimental botany · 2022Review
- Sphingolipid Δ4-desaturation is an important metabolic step for glycosylceramide formation in Physcomitrium patens.Journal of experimental botany · 2021Article
- Convergence of sphingolipid desaturation across over 500 million years of plant evolution.Nature plants · 2021Article
- Functions of Sphingolipids in Pathogenesis During Host-Pathogen Interactions.Frontiers in microbiology · 2021Review
- Glycosphingolipids in Filamentous Fungi: Biological Roles and Potential Applications in Cosmetics and Health Foods.Frontiers in microbiology · 2021Review
- Scedosporium Cell Wall: From Carbohydrate-Containing Structures to Host-Pathogen Interactions.Mycopathologia · 2020Review
- Fungal sphingolipids: role in the regulation of virulence and potential as targets for future antifungal therapies.Expert review of anti-infective therapy · 2020Review
- Article
- Review
- Plant-UniquePlants (Basel, Switzerland) · 2019Article
- Engineered Pichia pastoris production of fusaruside, a selective immunomodulator.BMC biotechnology · 2019Article
- Sphingolipid biosynthesis in man and microbes.Natural product reports · 2018Review
- Review
- Article
- Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.The Journal of membrane biology · 2017Article
- Analysis of sphingolipids, sterols, and phospholipids in human pathogenicJournal of lipid research · 2017Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the yeast Saccharomyces cerevisiae has only one sphingolipid class with a head group based on phosphoinositol, the yeast Pichia pastoris as well as many other fungi have a second class, glucosylceramide, which has a glucose head group. These two sphingolipid classes are in addition distinguished by a characteristic structure of their ceramide backbones. Here, we investigate the mechanisms controlling substrate entry into the glucosylceramide branch of the pathway. By a combination of enzymatic in vitro studies and lipid analysis of genetically engineered yeast strains, we show that the ceramide synthase Bar1p occupies a key branching point in sphingolipid biosynthesis in P. pastoris. By preferring dihydroxy sphingoid bases and C(16)/C(18) acyl-coenzyme A as substrates, Bar1p produces a structurally well defined group of ceramide species, which is the exclusive precursor for glucosylceramide biosynthesis. Correlating with the absence of glucosylceramide in this yeast, a gene encoding Bar1p is missing in S. cerevisiae. We could not successfully investigate the second ceramide synthase in P. pastoris that is orthologous to S. cerevisiae Lag1p/Lac1p. By analyzing the ceramide and glucosylceramide species in a collection of P. pastoris knock-out strains in which individual genes encoding enzymes involved in glucosylceramide biosynthesis were systematically deleted, we show that the ceramide species produced by Bar1p have to be modified by two additional enzymes, sphingolipid Δ4-desaturase and fatty acid α-hydroxylase, before the final addition of the glucose head group by the glucosylceramide synthase. Together, this set of four enzymes specifically defines the pathway leading to glucosylceramide biosynthesis.
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