Discovery of antimicrobial anthraquinones with membrane damaging effects from the endophytic fungus Stagonosporopsis sp.

This study is led by Prof. Liu (Institute of Microbiology, Chinese Academy of Sciences). Antimicrobial resistance, particularly methicillin-resistant Staphylococcus aureus (MRSA), poses a growing global health threat, with limited treatment options due to emerging resistance and adverse effects associated with conventional antibiotics. In this study, three new anthraquinone derivatives, stagonoquinones A–C (1–3), along with eleven known analogues, were isolated from the endophytic fungus Stagonosporopsis sp. YZHH‑J‑1 using a bioactivity‑guided approach combined with HSQC‑based DeepSAT analysis (Figure 1). Their structures, including absolute configurations, were elucidated by comprehensive spectroscopic analysis, NMR calculations with statistical protocols (CP3 and DP4+), and optical rotation calculations. Antimicrobial evaluation revealed that compound 1 exhibited moderate activity against MRSA. Mechanistic studies indicated that compound 1 inhibited MRSA by suppressing biofilm formation, disrupting membrane integrity, and inducing oxidative damage via ROS accumulation, with dihydrofolate reductase identified as a potential target (Figure 1). These findings not only enrich the structural diversity of fungal‑derived anthraquinones but also provide promising lead candidates for the development of antimicrobial agents against bacterial infections.