Small molecule target identification is a critical step in modern antibacterial drug discovery, particularly against multi-drug resistant pathogens. Albocycline (ALB) is a macrolactone natural product with potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA) whose mechanism of action has been elusive to date. Herein, we report biochemical and genomic studies that reveal ALB does not target bacterial peptidoglycan biosynthesis or the ribosome; rather, it appears to modulate NADPH ratios and upregulate redox sensing in the cell consistent with previous studies at Upjohn. Owing to the complexity inherent in biological pathways, further genomic assays are needed to identify the true molecular target(s) of albocycline.

小分子靶标识别是现代抗菌药物发现的关键步骤，特别是针对多重耐药病原体。Albocycline (ALB) 是一种大环内酯天然产物，对耐甲氧西林金黄色葡萄球菌(MRSA) 和耐万古霉素金黄色葡萄球菌(VRSA) 具有有效活性，但其作用机制迄今为止尚不清楚。在此，我们报告的生化和基因组研究表明 ALB 不靶向细菌肽聚糖生物合成或核糖体；相反，它似乎可以调节 NADPH 比率并上调细胞中的氧化还原感应，这与 Upjohn 之前的研究一致。由于生物途径固有的复杂性，需要进一步的基因组测定来鉴定白博环素的真正分子靶点。