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Chemical epigenetic manipulation was applied to a deep marine-derived fungus, Aspergillus sp. SCSIOW3, resulting in significant changes of the secondary metabolites. One new diphenylether-O-glycoside (diorcinol 3-O-α-D-ribofuranoside), along with seven known compounds, were isolated from the culture treated with a combination of histone deacetylase inhibitor (suberohydroxamic acid) and DNA methyltransferase inhibitor (5-azacytidine). Compounds 2 and 4 exhibited significant biomembrane protective effect of erythrocytes. 2 also showed algicidal activity against Chattonella marina, a bloom forming alga responsible for large scale fish deaths.