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

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 identifi...

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Autores principales: Iimura, Kurin, Furukawa, Tomohiro, Yamamoto, Toshiyoshi, Negishi, Lumi, Suzuki, Michio, Sakuda, Shohei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535166/
https://www.ncbi.nlm.nih.gov/pubmed/28704973
http://dx.doi.org/10.3390/toxins9070219
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author Iimura, Kurin
Furukawa, Tomohiro
Yamamoto, Toshiyoshi
Negishi, Lumi
Suzuki, Michio
Sakuda, Shohei
author_facet Iimura, Kurin
Furukawa, Tomohiro
Yamamoto, Toshiyoshi
Negishi, Lumi
Suzuki, Michio
Sakuda, Shohei
author_sort Iimura, Kurin
collection PubMed
description 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.
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spelling pubmed-55351662017-08-04 The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus Iimura, Kurin Furukawa, Tomohiro Yamamoto, Toshiyoshi Negishi, Lumi Suzuki, Michio Sakuda, Shohei Toxins (Basel) Article 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. MDPI 2017-07-12 /pmc/articles/PMC5535166/ /pubmed/28704973 http://dx.doi.org/10.3390/toxins9070219 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Iimura, Kurin
Furukawa, Tomohiro
Yamamoto, Toshiyoshi
Negishi, Lumi
Suzuki, Michio
Sakuda, Shohei
The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
title The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
title_full The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
title_fullStr The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
title_full_unstemmed The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
title_short The Mode of Action of Cyclo(l-Ala-l-Pro) in Inhibiting Aflatoxin Production of Aspergillus flavus
title_sort mode of action of cyclo(l-ala-l-pro) in inhibiting aflatoxin production of aspergillus flavus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5535166/
https://www.ncbi.nlm.nih.gov/pubmed/28704973
http://dx.doi.org/10.3390/toxins9070219
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