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Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells

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Abstract

Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol. This confirms that patE encodes the patulin synthase involved in the conversion of E-ascladiol to patulin. After purification, cytotoxicities of patulin and E- and Z-ascladiol were investigated on human cell lines from liver, kidney, intestine, and immune system. Patulin was cytotoxic for these four cell lines in a dose-dependent manner. By contrast, both E- and Z-ascladiol were devoid of cytotoxicity. Microarray analyses on human intestinal cells treated with patulin and E-ascladiol showed that the latter, unlike patulin, did not alter the whole human transcription. These results demonstrate that E- and Z-ascladiol are not toxic and therefore patulin detoxification strategies leading to the accumulation of ascladiol are good approaches to limit the patulin risk.

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Acknowledgements

J. Tannous and S. Snini were supported by doctoral fellowship from CNRS and Saint-Joseph University, Lebanon and MESR, France, respectively. This work was supported by the project CASDAR AAP RT 2015 No. 1523. We thank C. Naylies (GeT-TRiX Genopole) for her excellent technical assistance, the Cell Imaging Platform (M2C, ToxAlim) and the bioinformatics platform (Bioinfo Genotoul).

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    Authors and Affiliations

    1. Toxalim (Research Centre in Food Toxicology), INRA, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France

      Joanna Tannous, Selma P. Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, Isabelle P. Oswald & Olivier Puel

    2. ENVT, INP, UMR 1331, Toxalim, Université de Toulouse III, 31076, Toulouse, France

      Joanna Tannous, Selma P. Snini, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Yannick Lippi, Imourana Alassane-Kpembi, Thierry Gauthier, Isabelle P. Oswald & Olivier Puel

    3. Centre d’Analyses et de Recherches (Faculté des Sciences), Université Saint-Joseph, Campus des Sciences et Technologies, Mar Roukos, Mkallès, Riad El Solh, P.O. Box 11-514, Beirut, 1107 2050, Lebanon

      Joanna Tannous, Rhoda El Khoury, André El Khoury & Roger Lteif

    4. Laboratory of Microorganisms and Food Irradiation, Lebanese Atomic Energy Commission-CNRS, Riad El Solh, P.O. Box 11-8281, Beirut, 1107 2260, Lebanon

      Ali Atoui

    5. Laboratory of Microbiology, Department of Biology, Faculty of Sciences, Lebanese University, Hadath Campus, Beirut, Lebanon

      Ali Atoui

    6. Guelph Research and Development Center, Agriculture and Agri-Food Canada, 93 Stone Road West, Guelph, ON, Canada

      Ting Zhou

    7. INRA, UMR 1331 TOXALIM, 180, Chemin de Tournefeuille, 31027, Toulouse, France

      Olivier Puel

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    1. Joanna Tannous
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    Joanna Tannous and Selma P. Snini have contributed equally to this work.

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    Tannous, J., Snini, S.P., El Khoury, R. et al. Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells. Arch Toxicol 91, 2455–2467 (2017). https://doi.org/10.1007/s00204-016-1900-y

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