American Chemical Society (June 4, 2021)

Metabolite mining of environmentally collected aquatic and marine microbiomes offers a platform for the discovery of new therapeutic lead molecules. Combining a pre-fractionated chromatography library with liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based molecular networking and biological assays, we isolated and characterized two new micro-peptins (1 and 2) along with the previously characterized micro-peptin 996. These metabolites showed potency in anti-neuroinflammatory assays using BV-2 mouse microglial cells, showing a 50% reduction in inflammation in a range from 1 to 10 μM. These results show promise for cyanobacterial peptides in the therapeutic realm apart from their impact on environmental health and provide another example of the utility of large pre-fractionated natural product libraries for therapeutic hit and lead identification.