Identification of Fungal and Bacterial Denitrification Inhibitors Targeting Copper Nitrite Reductase

  • Ashutosh Kumar
    Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan
  • Masaki Matsuoka
    Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
  • Akihisa Matsuyama
    Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
  • Minoru Yoshida
    Chemical Genomics Research Group, RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
  • Kam Y. J. Zhang
    Laboratory for Structural Bioinformatics, Center for Biosystems Dynamics Research, RIKEN, 1-7-22 Suehiro, Tsurumi, Yokohama, Kanagawa 230-0045, Japan

書誌事項

公開日
2023-03-27
資源種別
journal article
権利情報
  • https://doi.org/10.15223/policy-029
  • https://doi.org/10.15223/policy-037
  • https://doi.org/10.15223/policy-045
DOI
  • 10.1021/acs.jafc.3c00896
公開者
American Chemical Society (ACS)

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説明

The usage of nitrification inhibitors is one of the strategies that reduce or slow down the denitrification process to prevent nitrogen loss to the atmosphere in the form of N2O. Directly targeting microbial denitrification could be one of the mitigation strategies; however, until now little efforts have been devoted toward the development of denitrification inhibitors. Here, we have identified small-molecule inhibitors of one of the proteins involved in the fungal denitrification pathway. Specifically, virtual screening was employed to identify the inhibitors of copper-containing nitrite reductase (FoNirK) of the filamentous fungus Fusarium oxysporum. Three series of chemical compounds were identified, out of which compounds belonging to two chemical scaffolds inhibited FoNirK enzymatic activity in low micromolar ranges. Several compounds also displayed moderate inhibition of fungal denitrification activity in vivo. Evaluation of in vitro activity against NirK from denitrifying bacterium Achromobacter xylosoxidans (AxNirK) and in vivo bacterial denitrification revealed a similar inhibitory profile.

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