Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus.
Dioctatin A (DotA), a metabolite of Streptomyces, is known to be an inhibitor of human dipeptidyl aminopeptidase II. Here, it was found that DotA strongly inhibited aflatoxin production by Aspergillus parasiticus, with an IC50 value of 4.0 microM. The mycelial growth of the fungus was not affected by the addition of DotA at a concentration of 50 microM, but inhibition of conidiation was observed at the same concentration. DotA inhibited production of norsolorinic acid, an early biosynthetic intermediate of aflatoxin, and it strongly reduced the mRNA levels of genes encoding aflatoxin biosynthetic enzymes, and significantly decreased the mRNA level of aflR, which encodes a key regulatory protein for aflatoxin biosynthesis. In addition to these genes, the mRNA level of brlA, which encodes a conidiation-specific transcription factor, was also reduced by the addition of DotA. It was also found that DotA dramatically enhanced kojic acid production by the fungus. Furthermore, DotA inhibited production of sterigmatocystin, which is a toxic aflatoxin biosynthetic intermediate, and it also inhibited conidiation in Aspergillus nidulans. These results indicate that DotA has pleiotropic effects on regulatory mechanisms of fungal secondary metabolite production and differentiation, leading to inhibition of aflatoxin production.
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Tomoya
T
Yoshinari
Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Tetsuo
T
Akiyama
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Keita
K
Nakamura
Department of Applied Bioscience, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.
Tatsuhiko
T
Kondo
Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Yoshikazu
Y
Takahashi
Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Yasuhiko
Y
Muraoka
Microbial Chemistry Research Center, 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo 141-0021, Japan.
Yoshiaki
Y
Nonomura
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Hiromichi
H
Nagasawa
Department of Applied Biological Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan.
Shohei
S
Sakuda
D000348:Aflatoxins / Q000096:biosynthesis*; D000880:Anthraquinones / Q000378:metabolism; D001230:Aspergillus / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D004151:Dipeptides / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D020128:Inhibitory Concentration 50; D011753:Pyrones / Q000378:metabolism; D012331:RNA, Fungal / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013172:Spores, Fungal / Q000187:drug effects; D013241:Sterigmatocystin / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
C113837:AFLR protein, Aspergillus; D000348:Aflatoxins; D000880:Anthraquinones; D004268:DNA-Binding Proteins; D004151:Dipeptides; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D011753:Pyrones; D012331:RNA, Fungal; D012333:RNA, Messenger; D014157:Transcription Factors; D013241:Sterigmatocystin; C011890:kojic acid; C002754:norsolorinic acid