The known RiPP natural product berninamycin C exhibits previously unidentified anti-inflammatory activity

Finding new therapeutic applications of known natural products remains a continuous endeavour in drug discovery. In this work, we report a strain of Streptomyces sp. PS-15, isolated from the soil of the Qinghai-Tibet Plateau. This strain produces berninamycin C as its main metabolite, which demonstrated potent antibacterial activity against Gram-positive bacteria, particularly Bacillus subtilis and Corynebacterium glutamicum, with an MIC <1.25 µM. Furthermore, both berninamycin C and D were found to significantly reduce the secretion of multiple inflammatory factors in RAW264.7 and A549 cells. Especially, berninamycin C and D at 25 µM showed 68.24% and 71.08% inhibition of inflammatory signalling in RAW264.7 cells. Both compounds exhibited low cytotoxicity in all tested cell lines, with IC₅₀ more than 200 µM. These findings highlight the potential of berninamycins as promising candidates for the development of novel anti-inflammatory therapeutics.