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Toxins 2017, 9(7), 219; doi:10.3390/toxins9070219

The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus

1
Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
2
Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Jiujiang Yu
Received: 21 June 2017 / Accepted: 11 July 2017 / Published: 12 July 2017
(This article belongs to the Collection Aflatoxins)
View Full-Text   |   Download PDF [1651 KB, uploaded 12 July 2017]   |  

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. View Full-Text
Keywords: aflatoxin; glutathione S-transferase; inhibitor; diketopiperazine; Aspergillus flavus aflatoxin; glutathione S-transferase; inhibitor; diketopiperazine; Aspergillus flavus
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Iimura, K.; Furukawa, T.; Yamamoto, T.; Negishi, L.; Suzuki, M.; Sakuda, S. The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus. Toxins 2017, 9, 219.

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