Naphpyrones A–H, Antibacterial Aromatic Polyketides Isolated from the <i>Streptomyces coelicolor</i> A3(2)/<i>spi1</i> Δ<i>spi</i>H3

<i>Staphylococcus aureus</i>, a common foodborne pathogen, has a close association with agriculture and food. With the rapid emergence and widespread dissemination of antimicrobial resistance, efforts have been directed toward developing and studying new antimicrobial compounds to inhibit the growth of <i>S. aureus</i> and other foodborne pathogens, thereby preventing contamination and ensuring food safety. Herein, we reported eight new aromatic polyketides, naphpyrones A-H (<b>1</b>-<b>8</b>), from the heterologous expression strain <i>Streptomyces coelicolor</i> A3(2)/<i>spi1</i> Δ<i>spi</i>H3. Their structures and absolute configurations were elucidated by extensive NMR, MS, theoretical NMR calculations, DP4+ probability analysis, Mosher's method, and ECD analyses. Notably, naphpyrone A (<b>1</b>) featured an unprecedented 6/6/6/6/5 neocyclic skeleton. Bioactivity evaluation revealed that compounds <b>1</b> and <b>2</b> exhibited antibacterial activity against <i>S. aureus</i>, with MIC values of 1 μg/mL and 4 μg/mL, respectively. These findings highlight the potential for screening and developing therapeutic agents from <i>actinomycetes</i>-derived aromatic polyketides against food pathogens.