Targeting Penicillium expansum transporters with high affinity small molecules for reducing patulin production

Fruits and vegetables represent an important component of a healthy diet. However, almost a third of all food crops could be annually lost because of fungal pathogens. Further more, the increase in resistance phenomena in fungi pushed the search of new molecules for controlling infections and related mycotoxins. Some of the newly proposed small mol ecules target fungal proteins with transporter ability. How ever, most of mycotoxin-producing fungi, as patulin-pro ducer Penicillium expansum, have few proteins with a solved structure to be used for identifying new inhibitors. Com putational approaches for protein function analyses might help in overcoming the problem, by building 3D homology models to be used in virtual screening of chemical libraries. In the present investigation, on the basis of generated 3D comparative models, it was possible to highlight approved drugs/natural compounds/chemicals able to inhibit GMC oxidoreductase and organic acid mitochondrial transporters to control P. expansum growth and patulin production. In particular, 1,2,3-BTA and tannic acid, predicted to inhibit mitochondrial transporters, and meticrane and 6-hydroxy coumarin, predicted to inhibit GMC oxidoreductase, proved to be efective in vitro and/or in vivo. A mixture of the iden tifed molecules could be used as disinfecting treatment in fruit washing water and storage rooms to prevent fungal infection and mycotoxin accumulation. Finally, the presented study might be extended to the identifcation of high afnity small molecules of species-specifc protein targets of other pathogenic fungi for preventing pre- and postharvest losses as well as for reducing the contamination by mycotoxins in fruit and vegetables.