The mode of action of cyclo(L-Ala-L-Pro) in inhibiting aflatoxin production of Aspergillus flavus

Abstract

Cyclo(L-Ala-L-Pro) inhibits aflatoxin production in aflatoxigenic fungi without affecting fungal growth. The mode of action of cyclo(L-Ala-L-Pro) in inhibiting aflatoxin production of Aspergillus flavus was investigated. A glutathione S-transferase (GST) of the fungus, designated AfGST, was identified as a binding protein of cyclo(L-Ala-L-Pro) in an experiment performed using cyclo(L-Ala-L-Pro)-immobilized Sepharose beads. Cyclo(L-Ala-L-Pro) specifically bound to recombinant AfGST and inhibited its GST activity. Ethacrynic acid, a known GST inhibitor, inhibited the GST activity of recombinant AfGST and aflatoxin production of the fungus. Ethacrynic acid reduced the expression level of AflR, a key regulatory protein for aflatoxin production, similar to cyclo(L-Ala-L-Pro). These results suggest that cyclo(L-Ala-L-Pro) inhibits aflatoxin production by affecting GST function in A. flavus, and that AfGST inhibitors are possible candidates as selective aflatoxin production inhibitors.