Iimura Kurin, Furukawa Tomohiro, Yamamoto Toshiyoshi, Negishi Lumi, Suzuki Michio, Sakuda Shohei
Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
Toxins (Basel). 2017 Jul 12;9(7):219. doi: 10.3390/toxins9070219.
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 was investigated. A glutathione -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 , and that AfGST inhibitors are possible candidates as selective aflatoxin production inhibitors.
环（L-丙氨酸-L-脯氨酸）可抑制产黄曲霉毒素真菌中黄曲霉毒素的产生，而不影响真菌生长。研究了环（L-丙氨酸-L-脯氨酸）抑制黄曲霉毒素产生的作用模式。在使用固定有环（L-丙氨酸-L-脯氨酸）的琼脂糖珠进行的实验中，该真菌的一种谷胱甘肽-S-转移酶（GST），命名为AfGST，被鉴定为环（L-丙氨酸-L-脯氨酸）的结合蛋白。环（L-丙氨酸-L-脯氨酸）特异性结合重组AfGST并抑制其GST活性。已知的GST抑制剂依他尼酸抑制重组AfGST的GST活性和该真菌的黄曲霉毒素产生。依他尼酸降低了黄曲霉毒素产生的关键调节蛋白AflR的表达水平，类似于环（L-丙氨酸-L-脯氨酸）。这些结果表明，环（L-丙氨酸-L-脯氨酸）通过影响该真菌中的GST功能来抑制黄曲霉毒素的产生，并且AfGST抑制剂可能是选择性黄曲霉毒素产生抑制剂的候选物。
