Abstract: Chemical epigenetic manipulation was applied to the zoanthid-derived fungus Cochliobolus lunatus (TA26-46) with a histone deacetylation modifier (100 μmolL⁻¹ nicotinamide), resulting in the isolation of a new 14-membered resorcylic acid lactone named 7′(Z)-zeaenol (1), together with six known analogues (2−7) from the treated broth. The planar structure of 1 was determined by comprehensive NMR spectroscopy and HRESIMS data. The absolute configuration of 1 was elucidated by ECD spectrum, ¹³C NMR shift calculations, and on the basis of biogenetic considerations. Compound 5 exhibited cytotoxic activity against the human tumor cell lines A549, HCT-116, HT-29, Hela, MCF-7, and K562 with the IC₅₀ values ranging from 2.54 to 7.44 μmolL⁻¹.