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1. Toxinogenesis

1.	Toxinogenesis
Patulin is the most common mycotoxin found in apples and apple-derived products such as juice, cider, compotes and other food intended for young children. Exposure to this mycotoxin is associated with immunological, neurological and gastrointestinal outcomes.

Assessment of the health risks due to patulin consumption by humans has led many countries to regulate the quantity in food. Patulin is a toxic chemical contaminant produced by several species of mould, especially within Aspergillus, Penicillium and Byssochlamys. Among the Aspergillus species, the number of patulin producing species is limited to three of the Clavati group: Aspergillus clavatus, A. giganteus and A. longivesica. For the Penicillium genus, after checking a significant number of isolates from each species and re-identification of certain isolates, a recent overview determined 13 patulin producing species: P. carneum, P. clavigerum, P. concentricum, P. coprobium, P. dipodomyicola, P. expansum, P. glandicola, P. gladioli, P. griseofulvum, P. marinum, P. paneum, P. sclerotigenum, P. vulpinum. In Byssochlamys/ Paecilomyces group, only B. nivea and some strains of Paecilomyces saturatus produce patulin. Among these species, P. expansum is responsible for the decay in pomaceous fruits (apples and pears) characterized by rapid soft rot and eventually by blue pustules. This species is considered as the main source of patulin in these fruits and consequently in apple derived products.
A full understanding of the molecular genetics of patulin biosynthesis is incomplete, unlike other regulated mycotoxins (aflatoxins, trichothecenes and fumonisins), although the chemical structures of patulin precursors are now known. On the basis of a large number of biochemical studies, the pathway almost complete of patulin biosynthesis has been determined (figure 1). Like several other major mycotoxins, e.g. aflatoxins, fumonisins and ochratoxins, patulin is a polyketide metabolite.


Our main aim is to elucidate and characterize the role of genes involved in the biosynthesis. We identified recently in Aspergillus clavatus genome, a cluster of 15 genes involved in patulin biosynthesis (figure 2) (Puel et al., 2010).


Previously, we isolated from Byssochlamys nivea, three genes encoding respectively a polyketide synthase (6-methylsalicylic acid synthase), an alcohol dehydrogenase (isoepoxydon dehydrogenase) (Puel et al., 2007) and an ATP Binding Cassette (ABC) transporter. This last gene has been also isolated from Penicillium griseofulvum and Penicillium expansum.
Finally genes encoding cytochrome P450 enzymes involved in two early steps of patulin pathway have been isolated from A. clavatus and characterized by heterologous expression in yeast (Artigot et al., 2009).