Tricholumin A (1) with an unprecedented carbon skeleton was isolated from the fungus Trichoderma asperellum cf44-2, an endophyte from the marine brown alga Sargassum sp. Its structure and relative configuration were identified by extensive 1D/2D NMR and mass spectrometric data, and the absolute configuration was assigned by X-ray diffraction and ECD calculations. Compound 1 represents a highly transformed ergosterol derivative, and it exhibited inhibition of some pathogenic microbes and marine phytoplankton species.