Dokument-ID Dokumenttyp Autoren/innen Persönliche Herausgeber/innen Haupttitel Abstract Auflage Verlagsort Verlag Herausgeber (Institution) Erscheinungsjahr Titel des übergeordneten Werkes Jahrgang/Band ISBN Veranstaltung Veranstaltungsort Beginndatum der Veranstaltung Enddatum der Veranstaltung Ausgabe/Heft Erste Seite Letzte Seite URN DOI Lizenz Datum der Freischaltung OPUS4-44424 Zeitschriftenartikel Borzekowski, Antje; Drewitz, T.; Keller, Julia; Pfeifer, Dietmar; Kunte, Hans-Jörg; Koch, Matthias; Rohn, S.; Maul, R. Biosynthesis and characterization of zearalenone-14-sulfate, zearalenone-14-glucoside and zearalenone-16-glucoside using common fungal strains Zearalenone (ZEN) and its phase II sulfate and glucoside metabolites have been detected in food and feed commodities. After consumption, the conjugates can be hydrolyzed by the human intestinal microbiota leading to liberation of ZEN that implies an underestimation of the true ZEN exposure. To include ZEN conjugates in routine analysis, reliable standards are needed, which are currently not available. Thus, the aim of the present study was to develop a facilitated biosynthesis of ZEN-14-sulfate, ZEN-14-glucoside and ZEN-16-glucoside. A metabolite screening was conducted by adding ZEN to liquid fungi cultures of known ZEN conjugating Aspergillus and Rhizopus strains. Cultivation conditions and ZEN incubation time were varied. All media samples were analyzed for metabolite formation by HPLC-MS/MS. In addition, a consecutive biosynthesis was developed by using Fusarium graminearum for ZEN biosynthesis with subsequent conjugation of the toxin by utilizing Aspergillus and Rhizopus species. ZEN-14-sulfate (yield: 49%) is exclusively formed by Aspergillus oryzae. ZEN-14-glucoside (yield: 67%) and ZEN-16-glucoside (yield: 39%) are formed by Rhizopus oryzae and Rhizopus oligosporus, respectively. Purities of ≥73% ZEN-14-sulfate, ≥82% ZEN-14-glucoside and ≥50% ZEN-16-glucoside were obtained by 1H-NMR. In total, under optimized cultivation conditions, fungi can be easily utilized for a targeted and regioselective synthesis of ZEN conjugates. Basel MDPI 2018 Toxins 10 3 Article 104, 1 15 urn:nbn:de:kobv:b43-444246 10.3390/toxins10030104 https://creativecommons.org/licenses/by/4.0/deed.de 2018-03-09 OPUS4-45577 Zeitschriftenartikel Keller, Julia; Borzekowski, Antje; Haase, H.; Menzel, R.; Rueß, L.; Koch, Matthias Toxicity assay for citrinin, zearalenone and zearalenone-14-sulfate using the nematode Caenorhabditis elegans as model organism To keep pace with the rising number of detected mycotoxins, there is a growing need for fast and reliable toxicity tests to assess the potential threat to food safety. Toxicity tests with the bacterial-feeding nematode Caenorhabditis elegans as model organism are well established. In this study the C. elegans wildtype strain N2 (var. Bristol) was used to investigate the toxic effects of the food-relevant mycotoxins citrinin (CIT) and zearalenone-14-sulfate (ZEA-14-S) and zearalenone (ZEA) on different life cycle parameters including reproduction, thermal and oxidative stress resistance and lifespan. The metabolization of the mycotoxins by the nematodes in vivo was investigated using HPLC-MS/MS. ZEA was metabolized in vivo to the reduced isomers α-zearalenol (α-ZEL) and β-ZEL. ZEA 14-S was reduced to α-/β-ZEL 14-sulfate and CIT was metabolized to mono-hydroxylated CIT. All mycotoxins tested led to a significant decrease in the number of nematode offspring produced. ZEA and CIT displayed negative effects on stress tolerance levels and for CIT an additional shortening of the mean lifespan was observed. In the case of ZEA-14-S, however, the mean lifespan was prolonged. The presented study shows the applicability of C. elegans for toxicity testing of emerging food mycotoxins for the purpose of assigning potential health threats. MDPI 2018 Toxins 10 7 284, 1 12 urn:nbn:de:kobv:b43-455772 10.3390/toxins10070284 https://creativecommons.org/licenses/by/4.0/deed.de 2018-07-25 OPUS4-43393 Zeitschriftenartikel Keller, Julia; Haase, H.; Koch, Matthias Hydroxylation and dimerization of zearalenone: comparison of chemical, enzymatic and electrochemical oxidation methods Investigations of the metabolic pathway of mycotoxins by microsomal techniques are often laborious, causing an increasing demand for easy and rapid simulation methods. Thus, the non-microsomal oxidation technique of electrochemistry coupled online to mass spectrometry (EC/MS) was applied to simulate phase I biotransformation of the Fusarium mycotoxin zearalenone (ZEA). The obtained transformation products were identified by high resolution mass spectrometry (FT-ICR) and HPLC-MS/MS. Transformation products (TPs) from EC/MS were compared to those of other oxidative methods such as Fenton-like and Ce(IV) reactions and metabolites derived from in vitro assays (human and rat liver microsomes). Electrochemical oxidization of ZEA was achieved by applying a potential between 0 and 2,500 mV vs. Pd/H2 using a flow-through cell with a boron-doped diamond working electrode. Several mono-hydroxylated TPs were generated by EC/MS and Fenton-like reaction, which could also be found in microsomal in vitro assays. EC and Ce(IV) led to the formation of structurally different ZEA dimers and dimeric quinones probably connected over covalent biaryl C-C and C-O-C bonds. Although the dimerization of phenolic compounds is often observed in natural processes, ZEA dimers have not yet been reported. This is the first report on the formation of stable ZEA dimers and their related quinones. The tested non-microsomal methods, in particular EC/MS, could be useful in order to predict the biotransformation products of mycotoxins, even in cases where one to one simulation is not always feasible. Wageningen Academic Publishers 2017 World Mycotoxin Journal 10 4 297 307 10.3920/WMJ2017.2213 2017-12-12 OPUS4-40492 Zeitschriftenartikel Keller, Julia; Haase, Hajo; Koch, Matthias Electrochemical simulation of biotransformation reactions of citrinin and dihydroergocristine compared to UV irradiation and Fenton-like reaction Mycotoxins occur widely in foodstuffs and cause a variety of mold-related health risks to humans and animals. Elucidation of the metabolic fate of mycotoxins and the growing number of newly discovered mycotoxins have enhanced the demand for fast and reliable simulation methods. The viability of electrochemistry coupled with mass spectrometry (EC/ESI-MS), Fenton-like oxidation, and UV irradiation for the simulation of oxidative phase I metabolism of the mycotoxins citrinin (CIT) and dihydroergocristine (DHEC) was investigated. The specific reaction products are compared with metabolites produced by human and rat liver microsomes in vitro. Depending on the applied potential between 0 and 2000 mV vs. Pd/H-2 by using a flow-through cell, CIT and DHEC are oxidized to various products. Besides dehydrogenation and dealkylation reactions, several hydroxylated DHEC and CIT species are produced by EC and Fenton-like reaction, separated and analyzed by LC-MS/MS and ESI-HRMS. Compared to reaction products from performed microsomal incubations, several mono- and dihydroxylated DHEC species were found to be similar to the reaction products of EC, Fenton-like reaction, and UV-induced oxidation. Consequentially, nonmicrosomal efficient and economic simulation techniques can be useful in early-stage metabolic studies, even if one-to-one simulation is not always feasible. Heidelberg Springer 2017 Analytical and Bioanalytical Chemistry 409 16 4037 4045 10.1007/s00216-017-0350-6 2017-06-12 OPUS4-47050 Zeitschriftenartikel Keller, Julia; Moldenhauer, Daniel; Byrne, L.; Haase, H.; Resch-Genger, Ute; Koch, Matthias Complexes of the mycotoxins citrinin and ochratoxin A with aluminum ions and their spectroscopic properties The sensitive detection of the mycotoxin citrinin (CIT) utilizing ist fluorescence requires approaches to enhance the emission. In this respect, we studied the complexation of CIT and ochratoxin A (OTA) with Al3+ in methanol using absorption and fluorescence spectroscopy. In this context, an isocratic high performance liquid chromatography (HPLC) method using a polymer column and a fluorescence detector was also developed that enables the separation of the metal ion complexes from the free ligands and non-complexed Al3+. CIT and OTA showed distinct changes in their absorption and fluorescence properties upon Al3+-coordination, and the fluorescence of CIT was considerably enhanced. Analysis of the photometrically assessed titration of CIT and OTA with Al3+ using the Job plot method revealed 1:2 and 1:1 stoichiometries for the Al3+ complexes of CIT (Al:CIT) and OTA (Al:OTA), respectively. In the case of CIT, only one -diketone moiety participates in Al3+ coordination. These findings can be elegantly exploited for signal amplification and provide the base to reduce the limit of detection for CIT quantification by about an order of magnitude, as revealed by HPLC measurements using a fluorescence detector. Basel MDPI 2018 Toxins 10 12 538, 1 8 urn:nbn:de:kobv:b43-470502 10.3390/toxins10120538 https://creativecommons.org/licenses/by/4.0/deed.de 2018-12-17 OPUS4-47410 Zeitschriftenartikel Kotthoff, Lisa; Keller, Julia; Lörchner, Dominique; Mekonnen, Tessema F.; Koch, Matthias Transformation products of organic contaminants and residues - Overview of current simulation methods The formation of transformation products (TPs) from contaminants and residues is becoming an increasing focus of scientific community. All organic compounds can form different TPs, thus demonstrating the complexity and interdisciplinarity of this topic. The properties of TPs could stand in relation to the unchanged substance or be more harmful and persistent. To get important information about the generated TPs, methods are needed to simulate natural and manmade transformation processes. Current tools are based on metabolism studies, photochemical methods, electrochemical methods, and Fenton's reagent. Finally, most transformation processes are based on redox reactions. This review aims to compare these methods for structurally different compounds. The groups of pesticides, pharmaceuticals, brominated flame retardants, and mycotoxins were selected as important residues/contaminants relating to their worldwide occurrence and impact to health, food, and environmental safety issues. Thus, there is an increasing need for investigation of transformation processes and identification of TPs by fast and reliable methods. Basel MDPI 2019 Molecules 24 4 753, 1 23 urn:nbn:de:kobv:b43-474108 10.3390/molecules24040753 https://creativecommons.org/licenses/by/4.0/deed.de 2019-02-21 OPUS4-46494 Zeitschriftenartikel Keller, Julia; Hantschke, Luisa; Haase, H.; Koch, Matthias Synthesis and Structural Identification of a Biaryl Ether-Linked Zearalenone Dimer A new dimer of the food-relevant mycotoxin zearalenone was isolated after electrochemical and chemical oxidation. The structure was determined as a 16-O-15'-biaryl ether-linked dimer based on spectroscopic analyses (1H- and 13C-NMR, COSY, HMBC, and HSQCAD) and high-Resolution mass spectrometry analysis (Q-TOF). Basel MDPI 2018 Molecules 23 10 2624 2628 urn:nbn:de:kobv:b43-464940 10.3390/molecules23102624 https://creativecommons.org/licenses/by/4.0/deed.de 2018-11-07 OPUS4-47858 Zeitschriftenartikel Keller, Julia; Borzekowski, Antje; Koch, Matthias Mykotoxine in Lebensmitteln - Zearalenon und seine Transformationsprodukte Mykotoxine in Lebensmitteln stellen weltweit Probleme dar, Zearalenon in Speiseöl ist ein solches. Neue Hydrazinbasierte Analyseverfahren können jetzt helfen, den EU-Grenzwert besser zu kontrollieren. Aber auch die Strukturaufklärung von Transformationsprodukten und verlässliche Kalibrierstandards sind aktuelle Herausforderungen. 2019 chrom+food forum 03 34 36 2019-04-24