To obtain new bioactive natural products, the effect of acidic stress on the metabolites of an aciduric fungus was investigated. This fungus, Penicillium sp. OUCMDZ-4736, which was isolated from the sediment around roots of mangrove (Acanthus ilicifolius), produced different compounds and higher yields under pH 2.5 than under neutral conditions. Using spectroscopic analyses and calculations, three new anthraquinone derivatives (1-3) were isolated and identified from the acidic fermentation broth (pH 2.5) of OUCMDZ-4736. Compound 1 showed much stronger anti-hepatitis B virus activity than that of the positive control, lamivudine, strongly inhibiting HBsAg and HBeAg secretion from HepG2.2.15 cells. These results show that extremophiles are a valuable resource of bioactive compounds, and that pH regulation is an effective strategy to induce metabolite production in aciduric fungi.
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