Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells
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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.
KeywordsAscladiol Patulin synthase Penicillium expansum patE gene Cytotoxicity Microarray analysis
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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Conflict of interest
The authors declare that they have no conflict of interest.
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