The Lactone Form of Stachybotrydial : A New Inhibitor of Dihydrofolate Reductase from Stachybotrys sp. FN298

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  • Kwon Yun-Ju
    Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology
  • Sohn Mi-Jin
    Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology
  • Kim Hyun-Ju
    Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology
  • Kim Won-Gon
    Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology

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  • The Lactone Form of Stachybotrydial: A New Inhibitor of Dihydrofolate Reductase from <i>Stachybotrys</i> sp. FN298

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Dihydrofolate reductase (DHFR) has been confirmed to be a novel target for antibacterial drug development. In this study, we determined that a fungal metabolite from Stachybotrys sp. FN298 can inhibit the DHFR of Staphylococcus aureus. Its structure was identified as a lactone form of stachybotrydial using mass spectrometry and nuclear magnetic resonance analysis. This compound inhibited S. aureus DHFR with a half-maximal inhibitory concentration of 41 µM. It also prevented the growth of S. aureus and methicillin-resistant S. aureus (MRSA) with a minimum inhibitory concentration of 32 µg·mL−1. To our knowledge, this is the first description of a DHFR inhibitor of microbial origin. The inhibitory function of the lactone form of stachybotrydial highlights its potential for development into a new broad-spectrum antibacterial agent and as an agent against MRSA.

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