Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells
- 486 Downloads
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Castoria R, Mannina L, Duran-Patron R, Maffei F, Sobolev AP, De Felice DV, Pinedo-Rivilla C, Ritieni A, Ferracane R, Wright SA (2011) Conversion of the mycotoxin patulin to the less toxic desoxypatulinic acid by the biocontrol yeast Rhodosporidium kratochvilovae strain LS11. J Agric Food Chem 59:11571–11578CrossRefPubMedGoogle Scholar
- Etxebeste O, Herrero-García E, Cortese MS, Garzia A, Oiartzabal-Arano E, De los Ríos V, Ugalde U, Espeso EA (2012) GmcA is a putative glucose–methanol–choline oxidoreductase required for the induction of asexual development in Aspergillus nidulans. PLoS ONE 7:e40292CrossRefPubMedPubMedCentralGoogle Scholar
- Ianiri G, Idnurm A, Wright SA, Duran-Patron R, Mannina L, Ferracane R, Ritieni A, Castoria R (2013) Searching for genes responsible for patulin degradation in a biocontrol yeast provides insight into the basis for resistance to this mycotoxin. Appl Environ Microbiol 79:3101–3115CrossRefPubMedPubMedCentralGoogle Scholar
- IARC (1986) Some naturally occuring and synthetic food components, furocoumarins and ultraviolet radiation. IARC Monogr Eval Carcinog Risks Hum 40:83–98Google Scholar
- JECFA (1995) Evaluation of certain food additives and contaminants. Forty-fourth report of the joint FAO/WHO expert committee on food additives. WHO Tech Rep Ser 859:36–38Google Scholar
- Steyn PS (1991) The biosynthesis of polyketide-derived mycotoxins. J Environ Pathol Toxicol Oncol 11:47–59Google Scholar
- Wright SAI, Ianiri DVG, Felice D, Castoria R, Berolini P (2007) A rapid assay for patulin degradation by the basidiomycetous yeast Rhodotorula glutinis strain LS11. In: Novel approaches for the control of postharvest diseases and disorders. Proceedings of the International Congress. Bologna, ItalyGoogle Scholar