| Summary: | Culturing ascidian-derived fungus <i>Amphichorda felina</i> SYSU-MS7908 under standard laboratory conditions mainly yielded meroterpenoid, and nonribosomal peptide-type natural products. We sequenced the genome of <i>Amphichorda felina</i> SYSU-MS7908 and found 56 biosynthetic gene clusters (BGCs) after bioinformatics analysis, suggesting that the majority of those BGCSs are silent. Here we report our genome mining effort on one cryptic BGC by heterologous expression in <i>Aspergillus oryzae</i> NSAR1, and the identification of two new α-pyrone derivatives, amphichopyrone A (<b>1</b>) and B (<b>2</b>), along with a known compound, udagawanone A (<b>3</b>). Anti-inflammatory activities were performed, and amphichopyrone A (<b>1</b>) and B (<b>2</b>) displayed potent anti-inflammatory activity by inhibiting nitric oxide (NO) production in RAW264.7 cells with IC<sub>50</sub> values 18.09 ± 4.83 and 7.18 ± 0.93 μM, respectively.
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