InChI=1S/C18H22O5/c1- 12-6-5-9-14(19)8-4-2-3-7-13-10-15(20)11-16(21)17(13)18(22)23-12/h3,7,10-12,20-21H,2,4-6,8-9H2,1H3/b7-3+/t12-/m0/s1 |
| MBMQEIFVQACCCH-QBODLPLBSA-N |
| C[C@H]1CCCC(=O)CCC\C=C\c2cc(O)cc(O)c2C(=O)O1 |
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fungal metabolite
Any eukaryotic metabolite produced during a metabolic reaction in fungi, the kingdom that includes microorganisms such as the yeasts and moulds.
mycoestrogen
Any compound produced by a fungus that happens to have estrogenic activity.
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View more via ChEBI Ontology
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(3S,11E)-14,16-dihydroxy-3-methyl-3,4,5,6,9,10-hexahydro-1H-2-benzoxacyclotetradecine-1,7(8H)-dione
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(-)-Zearalenone
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ChemIDplus
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(10S)-Zearalenone
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ChemIDplus
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(S)-(-)-Zearalenone
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ChemIDplus
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(S)-Zearalenone
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ChemIDplus
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(S-(E))-3,4,5,6,9,10-Hexahydro-14,16-dihydroxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione
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ChemIDplus
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6-(10-Hydroxy-6-oxo-trans-1-undecenyl)-beta-resorcylic acid lactone
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ChemIDplus
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trans-Zearalenone
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ChemIDplus
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zearalenone
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UniProt
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17924-92-4
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CAS Registry Number
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ChemIDplus
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4875541
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Reaxys Registry Number
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Reaxys
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Fruhauf S, Pühringer D, Thamhesl M, Fajtl P, Kunz-Vekiru E, Höbartner-Gussl A, Schatzmayr G, Adam G, Damborsky J, Djinovic-Carugo K, Prokop Z, Moll WD (2024)
Bacterial Lactonases ZenA with Noncanonical Structural Features Hydrolyze the Mycotoxin Zearalenone.
ACS catalysis 14, 3392-3410 [PubMed:38449531]
[show Abstract]
Zearalenone (ZEN) is a mycoestrogenic polyketide produced by Fusarium graminearum and other phytopathogenic members of the genus Fusarium. Contamination of cereals with ZEN is frequent, and hydrolytic detoxification with fungal lactonases has been explored. Here, we report the isolation of a bacterial strain, Rhodococcus erythropolis PFA D8-1, with ZEN hydrolyzing activity, cloning of the gene encoding α/β hydrolase ZenA encoded on the linear megaplasmid pSFRL1, and biochemical characterization of nine homologues. Furthermore, we report site-directed mutagenesis as well as structural analysis of the dimeric ZenARe of R. erythropolis and the more thermostable, tetrameric ZenAScfl of Streptomyces coelicoflavus with and without bound ligands. The X-ray crystal structures not only revealed canonical features of α/β hydrolases with a cap domain including a Ser-His-Asp catalytic triad but also unusual features including an uncommon oxyanion hole motif and a peripheral, short antiparallel β-sheet involved in tetramer interactions. Presteady-state kinetic analyses for ZenARe and ZenAScfl identified balanced rate-limiting steps of the reaction cycle, which can change depending on temperature. Some new bacterial ZEN lactonases have lower KM and higher kcat than the known fungal ZEN lactonases and may lend themselves to enzyme technology development for the degradation of ZEN in feed or food. | Murtaza B, Jin B, Wang L, Li X, Saleemi MK, Majeed S, Khatoon A, Xiao G, Xu Y (2024)
Mitigation of zearalenone in vitro using probiotic strains
Lebensmittel-Wissenschaft + [i.e. und] Technologie. Food science + technology. Science + technologie alimentaire 186, Not Available [Agricola:IND608145868]
[show Abstract]
Zearalenone (ZEN), a hazardous secondary metabolite produced by Fusarium, possesses an estrogen-like structure that triggers early pubertal changes and estrogenic diseases in animals. This research explores how physically treated Lactobacillus strains adsorb ZEN. According to the findings, four Lactobacillus strains—L1 (Lactobacillus plantae), L2 (Lactobacillus plantarum), L8 (Lactobacillus paracasei), and L9 (Lactobacillus acidophilus)—demonstrated evidence of ZEN adsorption and degradation in a 0.9% NaCl solution. Their activity ranged from 73% to 80% after 1 h, increasing to 86%–90% after 24 h. Among them, L9 exhibited the highest percentage of ZEN adsorption (90.39%), followed by L2 (88.68%), L1 (86.49%), and L8 (86.14%). Furthermore, LCMS/MS analysis revealed the involvement of the L8 and L1 strains in the degradation of ZEN into zearalenone sulfate (m/z 397.06) and α-zearalanol (α-ZAL m/z 321.13). According to FTIR analyses, the principal functional groups such as amides (C–N, CO), carboxyls (O–H, CO, or C–O), and alcohols (O–H) remained unaltered following ZEN adsorption, in comparison to heat-treated cells. These findings suggest that ZEN is hydrophobically adsorbed by Lactobacillus strains. Lactobacillus strains exhibited better ZEN reduction 87.27% and 91.7% after heat treatment, leading to modified bacterial cell shapes. Therefore, these four Lactobacillus strains could be considered natural adsorbents for removing ZEN from food products and feedstuffs. | Kawamura A, Westwood I, Wakefield L, Long H, Zhang N, Walters K, Redfield C, Sim E (2008)
Mouse N-acetyltransferase type 2, the homologue of human N-acetyltransferase type 1.
Biochemical pharmacology 75, 1550-1560 [PubMed:18280460]
[show Abstract]
There is increasing evidence that human arylamine N-acetyltransferase type 1 (NAT1, EC 2.3.1.5), although first identified as a homologue of a drug-metabolising enzyme, appears to be a marker in human oestrogen receptor positive breast cancer. Mouse Nat2 is the mouse equivalent of human NAT1. The development of mouse models of breast cancer is important, and it is essential to explore the biological role of mouse Nat2. We have therefore produced mouse Nat2 as a recombinant protein and have investigated its substrate specificity profile in comparison with human NAT1. In addition, we have tested the effects of inhibitors on mouse Nat2, including compounds which are endogenous and exogenous steroids. We show that tamoxifen, genistein and diethylstilbestrol inhibit mouse Nat2. The steroid analogue, bisphenol A, also inhibits mouse Nat2 enzymic activity and is shown by NMR spectroscopy, through shifts in proton peaks, to bind close to the active site. A three-dimensional structure for human NAT1 has recently been released, and we have used this crystal structure to generate a model of the mouse Nat2 structure. We propose that a conformational change in the structure is required in order for ligands to bind to the active site of the protein. | Kolf-Clauw M, Ayouni F, Tardieu D, Guerre P (2008)
Variations in zearalenone activation in avian food species.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46, 1467-1473 [PubMed:18221829]
[show Abstract]
Zearalenone (ZEA), a widely distributed oestrogenic fusariotoxin, constitutes a potential risk for human and animal health. ZEA is metabolised to the main metabolites identified in vitro and in vivo: alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). The efficiency to produce alpha-reduced metabolites appears of particular interest in risk assessment as alpha-reduced metabolites constitute activated forms whereas beta-reduced metabolites are less oestrogenic than ZEA. In this study ZEA activation was compared in avian food species. ZEA and its reduced metabolites were quantified in subcellular fractions of six avian species and rat livers. The alpha-ZOL/beta-ZOL ratio in rats was 19. The various avian food species cannot be considered to be equivalent in terms of ZEA reduction (P<0.001). Quails represented high "beta reducers", with alpha-ZOL/beta-ZOL ratio less than two. Weak "beta reducers" included on one part ducks and chickens showing alpha-ZOL/beta-ZOL ratio greater than 3 and up to 5.6 and on a second part geese, showing a lower production of alpha-ZOL than other poultry. Comparisons of enzyme kinetics in ducks and in quails show that these variations can be explained by the action of various isoforms of dehydrogenases. These results are relevant to food safety, in the context of frequently inevitable contamination of animal feed. | Videmann B, Mazallon M, Tep J, Lecoeur S (2008)
Metabolism and transfer of the mycotoxin zearalenone in human intestinal Caco-2 cells.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46, 3279-3286 [PubMed:18692541]
[show Abstract]
The mycotoxin zearalenone (ZEA) is found worldwide as contaminant in cereals and grains. It is implicated in reproductive disorders and hyperestrogenic syndromes in animals and humans exposed by food. We investigated metabolism and transfer of ZEA using the human Caco-2 cell line as a model of intestinal epithelial barrier. Cells exposed to 10-200 microM ZEA showed efficacious metabolism of the toxin. alpha-zearalenol and beta-zearalenol were the measured preponderant metabolites (respectively 40.7+/-3.1% and 31.9+/-4.9% of total metabolites, after a 3h exposure to 10 microM ZEA), whereas ZEA-glucuronide and alpha-zearalenol glucuronide were less produced (respectively 8.2+/-0.9% and 19.1+/-1.3% of total metabolites, after a 3h exposure to 10 microM ZEA). Cell production of reduced metabolites was strongly inhibited by alpha-and beta-hydroxysteroid dehydrogenase inhibitors, and Caco-2 cells exhibited alpha-hydroxysteroid dehydrogenase type II and beta-hydroxysteroid dehydrogenase type I mRNA. After cell apical exposure to ZEA, alpha-zearalenol was preponderantly found at the basal side, whereas beta-zearalenol and both glucuronides were preferentially excreted at the apical side. As alpha-zearalenol shows the strongest estrogenic activity, the preferential production and basal transfer of this metabolite suggests that intestinal cells may contribute to the manifestation of zearalenone adverse effects. | Tsakmakidis IA, Lymberopoulos AG, Khalifa TA, Boscos CM, Saratsi A, Alexopoulos C (2008)
Evaluation of zearalenone and alpha-zearalenol toxicity on boar sperm DNA integrity.
Journal of applied toxicology : JAT 28, 681-688 [PubMed:18027362]
[show Abstract]
This study aimed at investigating the in vitro effects of zearalenone (zen) and alpha-zearalenol (alpha-zen) on motility and nuclear chromatin integrity (NCI) of boar spermatozoa. Mycotoxins were tested, at levels ranging from 10 to 30 microg ml(-1) of diluted semen. Four boars were used for semen collection (eight replicates per boar, four per mycotoxin). After the addition of zen or alpha-zen, semen samples were incubated for 4 h at 38.5 degrees C, 5% CO(2) and 96% humidified air. Motility and NCI were assessed at 0 and 4 h of incubation. No significant differences were noticed in motility among the experimental groups (P > 0.05) for all tested boars. Chromatin instability was significantly higher (P < 0.05) in spermatozoa of only one boar treated with zen and alpha-zen independently of the dose. In conclusion, under our experimental conditions, zen and alpha-zen did not affect the motility of boar sperm, whereas the effects of these toxins on sperm NCI were individual-dependent. | Hassen W, Ayed-Boussema I, Oscoz AA, Lopez Ade C, Bacha H (2007)
The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells: oxidative DNA damage, gluthatione depletion and stress proteins induction.
Toxicology 232, 294-302 [PubMed:17339071]
[show Abstract]
Zearalenone (ZEN) is a fusarial mycotoxin with several adverse effects in laboratory and domestic animals including mainly estrogenicity. While most ZEN toxic effects have been quite well investigated, little is known regarding its mechanism of toxicity. Our previous investigations have shown the involvement of cytotoxicity, inhibition of macromolecules synthesis as well as genotoxicity. However, there are no available data regarding the involvement of the oxidative stress pathway in ZEN toxicity. In this context, the aim of this study was to find out whether ZEN induces oxidative cell damage. Using human hepatocytes Hep G2 cells, ZEN-induced stress response is monitored at several levels in these cells. ZEN mediated induction of oxidative DNA damage (comet assay using the repair enzymes), modulation of gluthatione (GSH), cytotoxicity (growth inhibition) and the oxidative stress responsive gene Hsp 70 and Hsp 90 were investigated with respect to concentration and time dependency. Hep G2 cells respond to ZEN exposure by loss of cell viability, induction of oxidative DNA damage, GSH depletion and Hsp 70 and Hsp 90 induction already at concentrations, which are not yet cytotoxic. The perturbation of the oxidative status was further confirmed by the significant reduction of the induced oxidative DNA damage as well as stress protein induction when cells were pre-treated with Vitamin E prior to exposure to ZEN. Our study clearly demonstrates that oxidative damage is likely to be evoked as one of the main pathway of ZEN toxicity. This oxidative damage may therefore be an initiating event and contribute, at least in part, to the mechanism of ZEN different genotoxic and cytotoxic effects. | Opara EI, Oehlschlager SL, Day L, Ridley SA, Vaughan R, Hanley AB (1999)
An In Vitro Cell Based Model for Assessing the Potential of Allergens to Release Mediators Through the Cross-linking of IgE.
Toxicology in vitro : an international journal published in association with BIBRA 13, 811-815 [PubMed:20654554]
[show Abstract]
The aim of this study was to examine the capacity of an in vitro model to test the potential of an allergen to cause cross-linking of IgE bound to the surface of mast cells. The model involved the passive sensitization of murine mast cells, with zearalenone IgE and subsequent exposure to anti IgE, zearalenone, zearalenone-BSA (with up to nine bound zearalenone molecules) or peanut lectin. The extent of cross-linking was determined by measuring the release of IgE mediators TNFalpha and histamine. Release of TNFalpha from IgE sensitized cells increased following exposure to zearalenone-BSA, but not following exposure to zearalenone alone or to peanut lectin. Histamine release could not be quantified against background. The results suggested that the model could be used to test allergenic potential through the availability of epitopes to bind and cross-link IgE on the surface of mast cells. As IgE is species specific, the model was adapted for use with a human cell system employing mast cells in lung fragments. TNFalpha release was measured, and the system was calibrated with the inhalant allergen from Timothy Grass and Timothy Grass specific IgE. |
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