Quality Control of Fungus-specific Glucosylceramide in Cryptococcus neoformans by Endoglycoceramidase-related Protein 1 (EGCrP1)

Ishibashi, Yoshihiro; Ikeda, Kazutaka; Sakaguchi, Koichiro; Okino, Nozomu; Taguchi, Ryo; Ito, Makoto

doi:10.1074/jbc.m111.311340

Cited by 28 publications

(33 citation statements)

References 58 publications

(27 reference statements)

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“…Compared to the sphingolipids found in various fungal species, the acyl chain length of the major sphingolipids in S. cerevisiae is very long (typically C 26 ), and this very long acyl chain is somehow crucial for S. cerevisiae (53,54). Interestingly, fungal GlcCer synthase exhibits strict structural specificity for the ceramide substrate, and the enzyme is likely incapable of using C 26 -ceramide as a substrate (8,17,55). Therefore, during the evolution of S. cerevisiae, as GlcCer synthesis became enzymatically incompatible with the synthesis of C 26 -sphingolipids, the ability to produce C 26 -sphingolipids might have been selected for, even at the expense of losing GlcCer.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggest that GlcCer and its metabolites are indispensable for normal mammalian development. In the pathogenic fungus Cryptococcus neoformans, mutations in genes relevant to GlcCer biosynthesis cause a partial reduction in growth, especially at alkaline pH (17). Therefore, GlcCer is essential for the growth of this fungus in host extracellular environments, which are characterized by a neutral/alkaline pH (18).…”

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confidence: 99%

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Glucosylceramide Contained in Koji Mold-Cultured Cereal Confers Membrane and Flavor Modification and Stress Tolerance to Saccharomyces cerevisiae during Coculture Fermentation

Sawada

Sato

Hamajima

et al. 2015

Appl Environ Microbiol

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fIn nature, different microorganisms create communities through their physiochemical and metabolic interactions. Many fermenting microbes, such as yeasts, lactic acid bacteria, and acetic acid bacteria, secrete acidic substances and grow faster at acidic pH values. However, on the surface of cereals, the pH is neutral to alkaline. Therefore, in order to grow on cereals, microbes must adapt to the alkaline environment at the initial stage of colonization; such adaptations are also crucial for industrial fermentation. Here, we show that the yeast Saccharomyces cerevisiae, which is incapable of synthesizing glucosylceramide (GlcCer), adapted to alkaline conditions after exposure to GlcCer from koji cereal cultured with Aspergillus kawachii. We also show that various species of GlcCer derived from different plants and fungi similarly conferred alkali tolerance to yeast. Although exogenous ceramide also enhanced the alkali tolerance of yeast, no discernible degradation of GlcCer to ceramide was observed in the yeast culture, suggesting that exogenous GlcCer itself exerted the activity. Exogenous GlcCer also increased ethanol tolerance and modified the flavor profile of the yeast cells by altering the membrane properties. These results indicate that GlcCer from A. kawachii modifies the physiology of the yeast S. cerevisiae and demonstrate a new mechanism for cooperation between microbes in food fermentation. In nature, microbial communities are formed through metabolic and physiochemical interactions among different microorganisms (1). The pH of cereals that have ripened and dropped from the husk to the ground is neutral to alkaline (2-4). Fermentation microbes, including Saccharomyces cerevisiae, Lactobacillus lactis, and Acetobacter aceti, efficiently utilize carbohydrates in the cereals to produce organic acids (1). As a result, the microbial communities that colonize such carbohydrate-rich cereals, as well as those found in fermented foods, reduce the pH to 4.0 to 6.0. After these microbes establish an acidic pH, they can dominate the environment because they can grow faster at acidic pH values than other microbes. Therefore, these microbes must first adapt to the alkaline environment at the initial stage of colonization on cereal; such adaptation mechanisms are also crucial for industrial fermentation.Traditional alcoholic beverages are produced via the fermentation of cereals by the yeast S. cerevisiae, which can efficiently catabolize glucose to produce ethanol. However, because S. cerevisiae is incapable of hydrolyzing starch to glucose, additional biological catalysts are often added to the fermentation reaction. For example, malt catalyzes starch hydrolysis in wheat-and barleyderived beverages such as whiskey and beer. In East and Southeast Asia, various cereals fermented by fungi are widely used as starchhydrolyzing catalysts for the production of rice-derived alcoholic beverages. These include Japanese sake (5, 6) and shochu, Korean Makgeolli, and Chinese Huangjiu, as well as various other fermented foods ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Glucosylceramide Contained in Koji Mold-Cultured Cereal Confers Membrane and Flavor Modification and Stress Tolerance to Saccharomyces cerevisiae during Coculture Fermentation

Sawada

Sato

Hamajima

et al. 2015

Appl Environ Microbiol

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“…The manual determination of the syntenic ortholog groups of the remaining ϳ5,400 Cryptococcus genes is an ongoing effort. Published names were applied across all species, even if they were not in the preferred 3-letter plus a number format, (e.g., the histone chaperone HIRA [7] and the fungus-specific glucosylceramide EGCrP1 [29]) (see the supplemental material). Adding an additional name to a gene to conform to a naming guideline only exacerbates the problem by associating more than one name with a single gene, a circumstance we hope to avoid.…”

Section: Resultsmentioning

confidence: 99%

Literature-Based Gene Curation and Proposed Genetic Nomenclature for Cryptococcus

et al. 2014

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cCryptococcus, a major cause of disseminated infections in immunocompromised patients, kills over 600,000 people per year worldwide. Genes involved in the virulence of the meningitis-causing fungus are being characterized at an increasing rate, and to date, at least 648 Cryptococcus gene names have been published. However, these data are scattered throughout the literature and are challenging to find. Furthermore, conflicts in locus identification exist, so that named genes have been subsequently published under new names or names associated with one locus have been used for another locus. To avoid these conflicts and to provide a central source of Cryptococcus gene information, we have collected all published Cryptococcus gene names from the scientific literature and associated them with standard Cryptococcus locus identifiers and have incorporated them into FungiDB (www.fungidb.org). FungiDB is a panfungal genome database that collects gene information and functional data and provides search tools for 61 species of fungi and oomycetes. We applied these published names to a manually curated ortholog set of all Cryptococcus species currently in FungiDB, including Cryptococcus neoformans var. neoformans strains JEC21 and B-3501A, C. neoformans var. grubii strain H99, and Cryptococcus gattii strains R265 and WM276, and have written brief descriptions of their functions. We also compiled a protocol for gene naming that summarizes guidelines proposed by members of the Cryptococcus research community. The centralization of genomic and literature-based information for Cryptococcus at FungiDB will help researchers communicate about genes of interest, such as those related to virulence, and will further facilitate research on the pathogen.

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“…grubii H99 database) was disrupted with the NAT split marker according to the method described previously (12,18). A gene-specific disruption cassette contained ϳ350 bp of the 5Ј-and 3Ј-flanking regions of egcrp2, an 860-bp fragment of the promoter sequence with the ATG start codon of the C. neoformans actin gene (19), a 310-bp fragment of the terminator sequence with the stop codon of C. neoformans TRP1 (20), and the selectable marker NAT gene (21) (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…EGCase very weakly hydrolyzes GlcCer, whereas EGCrP1 specifically hydrolyzes GlcCer but not oligosaccharide-linked GSLs, such as LacCer, GM1a, and Gb3Cer, which are favorite substrates for EGCase. Thus, EGCrP1 was the first identified GlcCer-degrading enzyme (glucocerebrosidase) in fungi (12). Although the disruption of egcrp1 in C. neoformans reduced glucocerebrosidase activity under neutral conditions, the activity remained almost unchanged under acidic conditions, suggesting the presence of other glucocerebrosidase(s) that function in C. neoformans under acidic conditions.…”

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confidence: 99%

Sterylglucoside Catabolism in Cryptococcus neoformans with Endoglycoceramidase-related Protein 2 (EGCrP2), the First Steryl-β-glucosidase Identified in Fungi

Watanabe

Ito

Goda

et al. 2015

Journal of Biological Chemistry

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Background: Endoglycoceramidase-related protein 1 (EGCrP1) is a glucocerebrosidase in Cryptococcus neoformans; however, the functions of its paralogue, EGCrP2, remain unknown. Results: EGCrP2, but not EGCrP1, hydrolyzed steryl-␤-glucosides. Disruption of egcrp2 accumulated ergosteryl-3␤-glucoside in C. neoformans. Conclusion: EGCrP2 degraded steryl-␤-glucosides both in vivo and in vitro.Significance: EGCrP2 is a missing link in steryl-␤-glucoside metabolism in fungi. In addition, EGCrP2 is a potential target for antifungal drugs.

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Quality Control of Fungus-specific Glucosylceramide in Cryptococcus neoformans by Endoglycoceramidase-related Protein 1 (EGCrP1)

Cited by 28 publications

References 58 publications

Glucosylceramide Contained in Koji Mold-Cultured Cereal Confers Membrane and Flavor Modification and Stress Tolerance to Saccharomyces cerevisiae during Coculture Fermentation

Glucosylceramide Contained in Koji Mold-Cultured Cereal Confers Membrane and Flavor Modification and Stress Tolerance to Saccharomyces cerevisiae during Coculture Fermentation

Literature-Based Gene Curation and Proposed Genetic Nomenclature for Cryptococcus

Sterylglucoside Catabolism in Cryptococcus neoformans with Endoglycoceramidase-related Protein 2 (EGCrP2), the First Steryl-β-glucosidase Identified in Fungi

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