Amplicon-based prediction of secondary metabolic potential of microbiomes facilitates natural product discovery.

The rapid exploration of natural products not only expands chemical diversity but also plays a vital role in drug discovery by identifying bioactive agents (e.g., antibiotics), revealing novel biological mechanisms, and providing new therapeutic opportunities. However, traditional techniques require extensive resources to screen and prioritize bacteria capable of producing valuable compounds from complex environmental samples. Here, we introduce the PSMPA (Predicting the Secondary Metabolism Potential using Amplicons) pipeline, designed to assess the secondary metabolic potential of microbiomes by estimating the abundance of biosynthetic gene cluster (BGC) classes based on 16S rRNA gene amplicons. This approach facilitates early-stage selection of samples and strains with high potential for novel compound production. We applied PSMPA to microbiome samples from marine environments (seawater, mangrove sediment, and intertidal flat sediment), leading to the identification of a promising Marinobacterium strain YM272 and the discovery of maripanthiones, a new class of sulfur-containing natural products. By enabling early identification of promising strains or samples, PSMPA accelerates novel natural product discovery and enhances the utility of amplicon sequencing for functional analysis. The web version of PSMPA is available at https://www.psmpa.net/.