1887

Abstract

Dioctatin A (DotA), a metabolite of , is known to be an inhibitor of human dipeptidyl aminopeptidase II. Here, it was found that DotA strongly inhibited aflatoxin production by , with an IC value of 4.0 μM. The mycelial growth of the fungus was not affected by the addition of DotA at a concentration of 50 μM, 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 , which encodes a key regulatory protein for aflatoxin biosynthesis. In addition to these genes, the mRNA level of , 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 . These results indicate that DotA has pleiotropic effects on regulatory mechanisms of fungal secondary metabolite production and differentiation, leading to inhibition of aflatoxin production.

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2007-08-01
2019-11-19
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References

  1. Bennett, J. W. & Klich, M. ( 2003; ). Mycotoxins. Clin Microbiol Rev 16, 497–516.[CrossRef]
    [Google Scholar]
  2. Bentley, R. ( 1957; ). Preparation and analysis of kojic acid. Methods Enzymol 3, 238–241.
    [Google Scholar]
  3. Boylan, M. T., Mirabito, P. M., Willett, C. E., Zimmerman, C. R. & Timberlake, W. E. ( 1987; ). Isolation and physical characterization of three essential conidiation genes from Aspergillus nidulans. Mol Cell Biol 7, 3113–3118.
    [Google Scholar]
  4. Calvo, A. M., Wilson, R. A., Bok, J. W. & Keller, N. P. ( 2002; ). Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev 66, 447–459.[CrossRef]
    [Google Scholar]
  5. Guzman-de-Pena, D. & Ruiz-Herrera, J. ( 1997; ). Relationship between aflatoxin biosynthesis and sporulation in Aspergillus parasiticus. Fungal Genet Biol 21, 198–205.[CrossRef]
    [Google Scholar]
  6. Ikeda, H., Matsumori, N., Ono, M., Suzuki, A., Isogai, A., Nagasawa, H. & Sakuda, S. ( 2000; ). Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus. J Org Chem 65, 438–444.[CrossRef]
    [Google Scholar]
  7. Kondo, T., Sakurada, M., Okamoto, S., Ono, M., Tsukigi, H., Suzuki, A., Nagasawa, H. & Sakuda, S. ( 2001; ). Effects of aflastatin A, an inhibitor of aflatoxin production, on aflatoxin biosynthetic pathway and glucose metabolism in Aspergillus parasiticus. J Antibiot (Tokyo) 54, 650–657.[CrossRef]
    [Google Scholar]
  8. Lee, L., Bennett, J. W., Goldblatt, L. A. & Lundin, R. E. ( 1971; ). Norsolorinic acid from a mutant strain of Aspergillus parasiticus. J Am Oil Chem Soc 48, 93–94.[CrossRef]
    [Google Scholar]
  9. Machida, M., Asai, K., Sano, M., Tanaka, T., Kumagai, T., Terai, G., Kusumoto, K., Arima, T., Akita, O. & other authors ( 2005; ). Genome sequencing and analysis of Aspergillus oryzae. Nature 438, 1157–1161.[CrossRef]
    [Google Scholar]
  10. Maes, M.-B., Martinet, W., Schrijvers, D. M., Van der Veken, P., De Meyer, G. R. Y., Augustyns, K., Lambeir, A.-M., Scharpe, S. & De Meester, I. ( 2006; ). Dipeptidyl peptidase II and leukocyte cell death. Biochem Pharmacol 72, 70–79.[CrossRef]
    [Google Scholar]
  11. Ono, M., Sakuda, S., Suzuki, A. & Isogai, A. ( 1997; ). Aflastatin A, a novel inhibitor of aflatoxin production by aflatoxigenic fungi. J Antibiot (Tokyo) 50, 111–118.[CrossRef]
    [Google Scholar]
  12. Ono, M., Sakuda, S., Ikeda, H., Furihata, K., Nakayama, J., Suzuki, A. & Isogai, A. ( 1998; ). Structures and biosynthesis of aflastatins: novel inhibitors of aflatoxin production by Aspergillus parasiticus. J Antibiot (Tokyo) 51, 1019–1028.[CrossRef]
    [Google Scholar]
  13. Payne, G. A. ( 1998; ). Process of contamination by aflatoxin-producing fungi and their impact on crops. In Mycotoxins in Agriculture and Food Safety, pp. 279–306. Edited by K. K. Sinha & D. Bhatnagar. New York: Marcel Dekker.
  14. Roze, L. V., Calvo, A. M., Gunterus, A., Beaudry, R., Kall, M. & Linz, J. E. ( 2004a; ). Ethylene modulates development and toxin biosynthesis in Aspergillus possibly via an ethylene sensor-mediated signaling pathway. J Food Prot 67, 438–447.
    [Google Scholar]
  15. Roze, L. V., Beaudry, R. M., Keller, N. P. & Linz, J. E. ( 2004b; ). Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in Aspergillus parasiticus. Mycopathologia 158, 219–232.[CrossRef]
    [Google Scholar]
  16. Sakuda, S., Ono, M., Furihata, K., Nakayama, J., Suzuki, A. & Isogai, A. ( 1996; ). Aflastatin A, a novel inhibitor of aflatoxin production of Aspergillus parasiticus, from Streptomyces. J Am Chem Soc 118, 7855–7856.[CrossRef]
    [Google Scholar]
  17. Sakuda, S., Ono, M., Ikeda, H., Sakurada, M., Nakayama, J., Suzuki, A. & Isogai, A. ( 1999; ). Aflastatins: new Streptomyces metabolites that inhibit aflatoxin biosynthesis. In Biologically Active Natural Products: agrochemicals, pp. 185–199. Edited by H. G. Cutler & S. J. Cutler. Boca Raton, FL: CRC Press.
  18. Sakuda, S., Ono, M., Ikeda, H., Nakamura, T., Inagaki, Y., Kawachi, R., Nakayama, J., Suzuki, A., Isogai, A. & Nagasawa, H. ( 2000a; ). Blasticidin A as an inhibitor of aflatoxin production by Aspergillus parasiticus. J Antibiot (Tokyo) 53, 1265–1271.[CrossRef]
    [Google Scholar]
  19. Sakuda, S., Ikeda, H., Nakamura, T., Kawachi, R., Kondo, T., Ono, M., Sakurada, M., Inagaki, H., Ito, R. & Nagasawa, H. ( 2000b; ). Blasticidin A derivatives with highly specific inhibitory activity toward aflatoxin production in Aspergillus parasiticus. J Antibiot (Tokyo) 53, 1378–1384.[CrossRef]
    [Google Scholar]
  20. Sakuda, S., Nakamura, K., Akiyama, T., Takahashi, Y., Muraoka, Y. & Kurata, I. ( 2006; ). Aflatoxin production inhibitor, and method for control of aflatoxin poisoning using the same. PCT Patent WO 2006137297 A1 20061228.
  21. Senten, K., der Veken, P. V., Bal, G., De Meester, I., Lambeir, A. M., Scharpe, S., Buvois, B., Haemersa, A. & Augustynsa, K. ( 2002; ). Development of potent and selective dipeptidyl peptidase II inhibitors. Bioorg Med Chem Lett 12, 2825–2828.[CrossRef]
    [Google Scholar]
  22. Shimizu, K., Hicks, J. K., Huang, T. P. & Keller, N. P. ( 2003; ). Pka, Ras and RGS protein interactions regulate activity of AflR, a Zn(II)2Cys6 transcription factor in Aspergillus nidulans. Genetics 165, 1095–1104.
    [Google Scholar]
  23. Takeuchi, T., Aoyanagi, T., Okami, Y., Osanawa, H., Iinuma, H. & Ogawa, K. ( 1991; ). Novel aminopeptidase-inhibiting dioctatins and their manufacture with Streptomyces species. Japanese Patent JP 03077857 A2 19910403 Heisei.
  24. Wieser, J., Yu, J. H. & Adams, T. H. ( 1997; ). Dominant mutations affecting both sporulation and sterigmatocystin biosynthesis in Aspergillus nidulans. Curr Genet 32, 218–224.[CrossRef]
    [Google Scholar]
  25. Woloshuk, C. P., Foutz, K. R., Brewer, J. F., Bhatnagar, D., Cleveland, T. E. & Payne, G. A. ( 1994; ). Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis. Appl Environ Microbiol 60, 2408–2414.
    [Google Scholar]
  26. Yabe, K. & Nakajima, H. ( 2004; ). Enzyme reactions and genes in aflatoxin biosynthesis. Appl Microbiol Biotechnol 64, 745–755.[CrossRef]
    [Google Scholar]
  27. Yan, P. S., Song, Y., Sakuno, E., Nakajima, H., Nakagawa, H. & Yabe, K. ( 2004; ). Cyclo(l-leucyl-l-prolyl) produced by Achromobacter xylosoxidans inhibits aflatoxin production by Aspergillus parasiticus. Appl Environ Microbiol 70, 7466–7473.[CrossRef]
    [Google Scholar]
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