%0 Journal Article
%T The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
%A Kurin Iimura
%A Lumi Negishi
%A Michio Suzuki
%A Shohei Sakuda
%A Tomohiro Furukawa
%A Toshiyoshi Yamamoto
%J Archive of "Toxins".
%D 2017
%R 10.3390/toxins9070219
%X 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
%K aflatoxin
%K glutathione S-transferase
%K inhibitor
%K diketopiperazine
%K Aspergillus flavus
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535166/