| Summary: | Overexpression of the histone acetyltransferase and the <sup>1</sup>H NMR spectroscopic experiments of the endophytic fungus <i>Monosporascus eutypoides</i> resulted in the isolation of two new compounds, monosporasols A (<b>1</b>) and B (<b>2</b>), and two known compounds, pestaloficin C (3) and arthrinone (<b>4</b>). Their planar structures and absolute configurations were determined by spectroscopic analysis including high resolution electrospray ionization mass spectroscopy (HRESIMS), one-dimensional (1D) and two-dimensional (2D) NMR, and calculated electronic circular dichroism data. Compounds <b>1–2</b> were screened in cytotoxic bioassays against HeLa, HCT-8, A549 and MCF-7 cells. Our work highlights the enormous potential of epigenetic manipulation along with the NMR comparison as an effective strategy for unlocking the chemical diversity encoded by fungal genomes.
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