Russian Journal of Genetics

, Volume 55, Issue 3, pp 301–308 | Cite as

Genomic Profiling of the Response of Aspergillus oryzae to the Treatment with Bis(2-Pyridine-1-Oxide) Diselenide

  • S. A. Zalepkina
  • V. F. SmirnovEmail author
  • A. V. Borisov
  • Zh. V. Matsulevich


We implemented genome-wide expression profiling to identify the mechanisms of toxicity of an organoselenium compound bis(2-pyridine-1-oxide) diselenide to the fungus А. oryzae RIB40. We uncovered changes in the expression levels in 72 genes. In particular, we observed a downregulation in the levels of several copper ion transmembrane transporter genes. In turn, we found a significant upregulation in the genes encoding oxidoreductases. The latter results are supported by biochemical experiments that revealed an increase in oxidoreductase activity in response to bis(2-pyridine-1-oxide) diselenide treatment. The results of a large-scale microarray analysis of the А. oryzae RIB 40 were confirmed by real-time quantitative PCR.


gene expression fungi organoselenium compounds DNA microarray examination PCR oxidoreductases 



We are grateful to Prof. K. Gomi and the staff of the Bioindustrial Genomics Department of Tohoku University for providing the opportunities to conduct experiments and for consultations regarding these studies.


The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.


  1. 1.
    Bhowmick, D. and Mugesh, G., Enzyme mimetic chemistry of organoselenium compounds, in Patai’s Chemistry of Functional Groups, Chichester, UK: Wiley, 2013. pp. 1175—1235.
  2. 2.
    Ninomiya, M., Garud, D.R., and Koketsu, M., Biologically significant selenium- containing heterocycles, Coord. Chem. Rev., 2011, vol. 255, pp. 2968—2990. CrossRefGoogle Scholar
  3. 3.
    Piętka-Ottlik, M., Wójtowicz-Młochowska, H., Kołodziejczyk, K., et al., New organoselenium compounds active against pathogenic bacteria, fungi and viruses, Chem. Pharm. Bull., 2008, vol. 56, no. 10, pp. 1423—1427. CrossRefGoogle Scholar
  4. 4.
    Henderson, R., Rothgery, E.F., and Schnieder, H.A., US Patent 4496559, 1985.Google Scholar
  5. 5.
    Mániková, D., Vlasáková, D., Loduhová, J., et al., Investigations on the role of base excision repair and non-homologous end-joining pathways in sodium selenite-induced toxicity and mutagenicity in Saccharomyces cerevisiae, Mutagenesis, 2009, vol. 25, no. 2, pp. 155—162. CrossRefGoogle Scholar
  6. 6.
    Wu, Z.L., Yin, X.B., and Lin, Z.Q., Inhibitory effect of selenium against Penicillium expansum and its possible mechanisms of action, Curr. Microbiol., 2014, vol. 69, no. 2, pp. 192—201. CrossRefGoogle Scholar
  7. 7.
    Koltovaya, N.A., Nikulushkina, Yu.V., Kadyshevskaya, E.Yu., et al., Interaction between checkpoint genes RAD9, RAD17, RAD24, RAD53, and genes SRM5/CDC28, SRM8/NET1, and SRM12/HFI1 involved in the determination of yeast Saccharomyces cerevisiae sensitivity to ionizing radiation, Russ. J. Genet., 2008, vol. 44, no. 8, pp. 909—918. CrossRefGoogle Scholar
  8. 8.
    De Backer, M.D., Ilyina, T., Ma, X.J., et al., Genomic profiling of the response of Candida albicans to itraconazole treatment using a DNA microarray. Antimicrob. Agents Chemother., 2001, vol. 45, no. 6, pp. 1660—1670. CrossRefGoogle Scholar
  9. 9.
    Liu, T.T., Lee, R.E.B., Barker, K.S., et al., Genome-wide expression profiling of the response to azole, polyene, echinocandin, and pyrimidine antifungal agents in Candida albicans, Antimicrob. Agents Chemother., 2005, vol. 49, pp. 2226—2236. CrossRefGoogle Scholar
  10. 10.
    Meyer, V., Damveld, R.A., Arentshorst, M., et al., Survival in the presence of antifungals: genome-wide expression profiling of Aspergillus niger in response to sublethal concentrations of caspofungin and fenpropimorph, J. Biol. Chem., 2007, vol. 282, pp. 32935—32948. CrossRefGoogle Scholar
  11. 11.
    Mautner, H., Chu, Sh., and Lee, C.M., Studies of 2-selenopyridine and related compounds, J. Org. Chem., 1962, vol. 27, pp. 3671—3673. CrossRefGoogle Scholar
  12. 12.
    Terabayashi, Y., Sano, M., Yamane, N., et al., Identification and characterization of genes responsible for biosynthesis of kojic acid, an industrially important compound from Aspergillus oryzae, Fungal Genet. Biol., 2010, vol. 47, no. 12, pp. 953—961. CrossRefGoogle Scholar
  13. 13.
    Kubodera, T., Nobuo, Y., and Akira, N., Pyrithiamine resistance gene (ptrA) of Aspergillus oryzae: cloning, characterization and application as a dominant selectable marker for transformation, Biosci., Biotechnol., Biochem., 2000, vol. 64, no. 7, pp. 1416−1421. CrossRefGoogle Scholar
  14. 14.
    Li, Y. and Shellhorn, H.E., Rapid kinetic microassay for catalase activity, J. BiomolTech., 2007, vol. 18, no. 4, pp. 185−187.Google Scholar
  15. 15.
    Flurkey, W.H., Ratcliff, B., Lopez, L., et al., Differentiation of fungal tyrosinases and laccases using selective inhibitors and substrates, Enzym. Browning Its Prev., 1995, vol. 6, pp. 81−89. CrossRefGoogle Scholar
  16. 16.
    Nagaraja, P., Shivakumar, A., and Kumar, S.A., Development and evaluation of kinetic spectrophotometric assays for horseradish peroxidase by catalytic coupling of paraphenylenediamine and mequinol, AnalSci., 2009, vol. 25, no. 10, pp. 1243−1248. Google Scholar
  17. 17.
    Data for Biochemical Research, Dawson, R.M.C., Elliott, D.C., Elliott, W.H., and Jones, K.M., Eds., New York: Oxford Univ. Press, 1986, 3rd ed. doi 10.1271/bbb.64.1416Google Scholar
  18. 18.
    Kobzar, A.I., Prikladnaya matematicheskaya statistika (Applied Mathematical Statistics), Moscow: Fizmatlit, 2006.Google Scholar
  19. 19.
    Zalepkina, S.A., Artem’eva, M.M., Bezrukov, M.E., et al., The use of selenium-containing heterocyclic compounds for protecting paints and varnishes from microbiological damage, Ekol. Prom-st. Ross., 2018, vol. 1, pp. 56—61. Google Scholar
  20. 20.
    Herrero Perpiñán, E. and Wellinger, R.E., Yeast as a model system to study metabolic impact of selenium compounds, Microb. Cell, 2015, vol. 2, no. 5, pp. 139—149. CrossRefGoogle Scholar
  21. 21.
    Bockhorn, J., Balar, B., He, D., et al., Genome-wide screen of Saccharomyces cerevisiae null allele strains identifies genes involved in selenomethionine resistance, Proc. Natl. Acad. Sci. U.S.A., 2008, vol. 105, no. 46, pp. 17682—17687. CrossRefGoogle Scholar
  22. 22.
    Rao, Y., McCooeye, M., Windust, A., et al., Mapping of selenium metabolic pathway in yeast by liquid chromatography-orbitrap mass spectrometry, Anal. Chem., 2010, vol. 82, no. 19, pp. 8121—8130. CrossRefGoogle Scholar
  23. 23.
    Kim, Y.H., Lee, H.S., Kwon, H.J., et al., Effects of different selenium levels on growth and regulation of laccase and versatile peroxidase in white-rot fungus, Pleurotus eryngii, World J Microbiol Biotechnol., 2014, vol. 30, no. 7, pp. 2101—2109. CrossRefGoogle Scholar
  24. 24.
    Nunes, R.G.F.L., Luz, J.M.R., Fantuzzi, E., et al., Mycelial growth of Pleurotus spp. in Se-enriched culture media, Adv. Microbiol., 2013, vol. 3, pp. 31—36. CrossRefGoogle Scholar
  25. 25.
    Ilyin, D.Yu., Ilyina, G.V., and Morozova, M.I., The perspectives of selenium compounds’ use in the conservation of collection cultures of xylotrophic basidiomycetes. Izv. Saratov Univ. Nov. Ser. Ser. Khim. Biol. Ecol., 2012, vol. 12, no. 1, pp. 56—60.Google Scholar

Copyright information

© Pleiades Publishing, Inc. 2019

Authors and Affiliations

  • S. A. Zalepkina
    • 1
  • V. F. Smirnov
    • 1
    Email author
  • A. V. Borisov
    • 2
  • Zh. V. Matsulevich
    • 2
  1. 1.Department of Biochemistry and Biotechnology, Lobachevsky State University of Nizhny NovgorodNizhny NovgorodRussia
  2. 2.Department of Industrial Safety, Ecology, and Chemistry, Nizhny Novgorod State Technical UniversityNizhny NovgorodRussia

Personalised recommendations