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Found 1 structure.
Displayed structure 1
| R-2HOSte-(1-2)-+ | b-D-Glcp-(1-1)-S,R-9b1SphdC19 | Show graphically |
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Structure type: monomer
C43H81O9N
Trivial name: cerebroside C, cerebroside D
Compound class: glycolipid, glycosphingolipid, glycoside, cerebroside, ceramide
Contained glycoepitopes: IEDB_137339,IEDB_142488,IEDB_146664,IEDB_983931,SB_192,SB_5
Background: Natural products acquire vast and intriguing structural diversity and have been recognized as a tremendously diverse source of new lead compounds. Numerous bioactive secondary metabolites are present in the form of glycosylated molecules in which the sugar parts are normally associated with the interaction along with molecular recognition of the cellular target. Scope and approach: The presence of sugar entities are crucial as well as in some cases necessary, for therapeutic effects. Establishing novel and potent glycosylated secondary metabolites has formed a main goal in the natural product field from fungi and bacteria. These compounds possess a diverse range of sugar units. Key findings and conclusions: Fungi is considered one of the important sources for approved drugs with a diverse range of mode of action. The sugar part in numerous pharmacologically active natural products enhances bioavailability, biological potential, reduce toxicity, and improve stability. The vast majority of glyocosides showed antimicrobial effects, cytotoxic, antiviral and antiinflammatory effects. Notably, numerous fungal glycosides presented in this review illustrate significant antimicrobial effects towards various microorganisms especially against plant pathogens. The antimicrobial effects of these fungal glycosides indicate that these metabolites could be employed as natural preservatives in food in order to abolish or control the growth of pathogenic and spoilage microorganisms.
glycoside, antimicrobial, fungi, food preservative, secondary metabolites
Publication DOI: 10.1016/j.tifs.2021.02.029Although 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.
structure, lipid, glycolipid, glycolipids, mass spectrometry (MS), glucosylceramide, sphingolipid, Gene Knock-out, Biosynthetic Pathway Ceramide, Ceramide Synthase
NCBI PubMed ID: 21303904A fungus-specific glucosylceramide (GlcCer), which contains a unique sphingoid base possessing two double bonds and a methyl substitution, is essential for pathogenicity in fungi. Although the biosynthetic pathway of the GlcCer has been well elucidated, little is known about GlcCer catabolism because a GlcCer-degrading enzyme (glucocerebrosidase) has yet to be identified in fungi. We found a homologue of endoglycoceramidase tentatively designated endoglycoceramidase-related protein 1 (EGCrP1) in several fungal genomic databases. The recombinant EGCrP1 hydrolyzed GlcCer but not other glycosphingolipids, whereas endoglycoceramidase hydrolyzed oligosaccharide- linked glycosphingolipids but not GlcCer. Disruption of egcrp1 in Cryptococcus neoformans, a typical pathogenic fungus causing cryptococcosis, resulted in the accumulation of fungus-specific GlcCer and immature GlcCer that possess sphingoid bases without a methyl substitution concomitant with a dysfunction of polysaccharide capsule formation. These results indicated that EGCrP1 participates in the catabolism of GlcCer and especially functions to eliminate immature GlcCer in vivo that are generated as by-products due to the broad specificity of GlcCer synthase. We conclude that EGCrP1, a glucocerebrosidase identified for the first time in fungi, controls the quality of GlcCer by eliminating immature GlcCer incorrectly generated in C. neoformans, leading to accurate processing of fungus-specific GlcCer.
glycosphingolipid, Cryptococcus neoformans, glucosylceramide, EGCase II
NCBI PubMed ID: 22072709Chemical investigation of the methanolic extract from the fruiting bodies of Hericium erinaceus, led to the isolation of fifty-one compounds including thirty-five ergostane-type sterols (1-35), fourteen aromatic compounds (36-49), and two cerebrosides (50 and 51). Their structures were identified based on spectroscopic analyses and by comparison of their spectral data with those reported in literature. This is the first comprehensive low-polarity chemical investigation of H. erinaceus. Thirty-one of the compounds (6-8, 11-35, 39, 41, and 49) were isolated for the first time from the genus Hericium and the family Hericiaceae. The chemotaxonomic relationship between H. erinaceus and other Hericium species was also discussed.
Hericium erinaceus, cerebroside, sterol, Hericiaceae, aromatic compound
Publication DOI: 10.1016/j.bse.2016.12.011Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-D-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12). Among them, compounds 1 and 11 were isolated as naturally occurring products for the first time, though they were reported as synthetic products in previous papers. All of the compounds (except 8 and 11) abrogated cisplatin-induced LLC-PK1 cell damage in a dose-dependent manner. Of special note, compounds 2, 5, 6, and 12 ameliorated cisplatin-induced nephrotoxicity to 80% of the control value at 10μM. The protective effects of compounds 2, 5, 6, and 12 were mediated via the deactivation of JNK-caspase 3 apoptotic cascade. This study is the first to demonstrate that the chemical constituents of P. cornucopiae display renoprotective effects against anticancer drug-induced damage in kidney cells.
mushroom, MAPKs, nephrotoxicity, Pleurotaceae, Pleurotus cornucopiae
NCBI PubMed ID: 28129885The pathogenic fungus Cryptococcus neoformans causes cryptococcosis, an opportunistic infectious disease resulting in 600,000 deaths per year. The two major glycolipids in C. neoformans are glucosylceramide (GlcCer) with a fungus-specific ceramide (methyl d18 : 2/h18 : 0) and ergosteryl β-glucoside (EG); however, the catabolic pathway of these glycolipids has not yet been uncovered. We found two homologues of endoglycoceramidase (EGCase, EC 3.2.1.123) in C. neoformans, designated Endoglycoceramidase-related Protein 1 and 2 (EGCrP1 and EGCrP2). EGCase hydrolyzes the O-glycosidic linkage between oligosaccharides and ceramides in various glycosphingolipids. However, EGCrP1 and EGCrP2 show completely different specificities; that is, EGCrP1 is a neutral glucocerebrosidase specific to GlcCer, whereas EGCrP2 is an acid β-glucosidase capable of hydrolyzing not only GlcCer but also various β-glucosides, including pNP β-glucoside and EG. Using each disruption mutant of egcrp1 and egcrp2, we elucidated that EGCrP1 plays an integral role in quality control of the fungus-specific GlcCer by eliminating immature GlcCer, which are byproducts of the GlcCer synthesis pathway, whereas EGCrP2 is involved in the catabolism of EG in the vacuoles of C. neoformans. The analysis of egcrp1-disrupted mutants also revealed that the quality control of fungus-specific GlcCer is strongly linked to the formation of the polysaccharide capsule, an important virulence factor. On the other hand, the disruption of EG catabolism resulted in growth arrest, dysfunction in cell budding, and abnormal vacuole morphology. These results indicate that catabolism of two different glycolipids plays different physiological roles in C. neoformans and strongly suggest EGCrP1 and EGCrP2 as targets for anti-cryptococcal drugs with a new mechanism of action
capsule, Cryptococcus neoformans, sterylglucoside, glycolipid catabolism, glucosylceramide quality control, vacuole
Publication DOI: 10.4052/tigg.1504.1ETwo new sesterterpenoids, terretonins H(1) and I(2), together with two known compounds, strobilactone A(3) and cerebroside D(4), were isolated from the lipophilic extract of the marine-derived fungus Aspergillus ustus KMM 4664. The structures of compounds 1 and 2 were determined based on spectroscopic methods and confirmed by X-ray crystallographic analysis of terretonin H. All compounds were tested for cytotoxic and embryotoxic effects using sperm and developing embryos of the sea urchin Strongylocentrotus intermedius and human cancer cells.
terretonin, sesterterpenoids, Aspergillus ustus, Strongylocentrotus intermedius
Publication DOI: 10.1016/j.phytol.2016.07.002So far, more than 20 species of Ganoderma (Lingzhi) fungi have been studied, including G. lucidum, G. sinense, G. japonicum, G. capense, G. australe, G. tsugae, G. applanatum, G. tropicus, G. boniense, G. duropora, G. resinaceum, G. theaecolum, G. cochlear, G. atrum, G. formosanum, G. boninense, G. colossum, G. concinna, G. amboinense, G. pfeifferi, and G. orbiforme. Over 600 compounds were isolated and identified from the genus Ganoderma. The components in Ganoderma contained triterpenes, meroterpenoids, steroids, alkaloids, nucleosides, nucleobases, and polysaccharides, in which triterpenes were the main compounds, and more than 300 triterpenes obtained from it. With the use of new technology of separation and purification, the other types of compounds, such as meroterpenoids, alkaloids, nucleosides, and polysaccharides were reported in recent years. Herein, the structural classifications and characteristics and separation methods were summarized.
polysaccharides, meroterpenoids, steroids, Ganoderma, triterpenes, alkaloids and nucleosides
NCBI PubMed ID: 31677140The membrane sphingolipid glucosylceramide (GlcCer) plays an important role in fungal fitness and adaptation to most diverse environments. Moreover, reported differences in the structure of GlcCer between fungi, plants and animals render this pathway a promising target for new generation therapeutics. Our knowledge about the GlcCer biosynthesis in fungi is mainly based on investigations of yeasts, whereas this pathway is less well characterized in molds. We therefore performed a detailed lipidomic profiling of GlcCer species present in Neurospora crassa and comprehensively show that the deletion of genes encoding enzymes involved in GlcCer biosynthesis affects growth, conidiation and stress response in this model fungus. Importantly, our study evidences that differences in the pathway intermediates and their functional role exist between N. crassa and other fungal species. We further investigated the role of GlcCer in the susceptibility of N. crassa toward two small cysteine-rich and cationic antimicrobial proteins (AMPs), PAF and PAFB, which originate from the filamentous ascomycete Penicillium chrysogenum. The interaction of these AMPs with the fungal plasma membrane is crucial for their antifungal toxicity. We found that GlcCer determines the susceptibility of N. crassa toward PAF, but not PAFB. A higher electrostatic affinity of PAFB than PAF to anionic membrane surfaces might explain the difference in their antifungal mode of action.
sphingolipids, lipidomics, glucosylceramide, Neurospora crassa, Penicillium chrysogenum, antimicrobial proteins
NCBI PubMed ID: 31031714Fusaruside is an immunomodulatory fungal sphingolipid which has medical potentials for treating colitis and liver injury, but its poor natural abundance limits its further study. In this study, we described a synthetic biology approach for fusaruside production by engineered Pichia pastoris that was based on polycistronic expression. Two fusaruside biosynthesis genes (Δ3(E)-sd and Δ10(E)-sd), were introduced into P. pastoris to obtain fusaruside producing strain FUS2. To further enhance the yield of fusaruside, three relevant biosynthetic genes (Δ3(E)-sd, Δ10(E)-sd and gcs) were subsequently introduced into P. pastoris to obtain FUS3. All of the biosynthetic genes were successfully co-expressed in FUS2 and FUS3. Compared to that produced by FUS2, fusaruside achieved from FUS3 were slightly increased. In addition, the culture conditions including pH, temperature and methanol concentration were optimized to improve the fusaruside production level. Here a novel P. pastoris fusaruside production system was developed by introducing the biosynthetic genes linked by 2A peptide gene sequences into a polycistronic expression construct, laying a foundation for further development and application of fusaruside.
optimization, fusaruside, co-expression, P. pastoris
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