Simone, M.; Iorio, M.; Monciardini, P.; Santini, M.; Cantu, N.; Tocchetti, A.; Serina, S.; Brunati, C.; Vernay, T.; Gentile, A.; Aracne, M.; Cozzi, M.; van der Hooft, J.; Sosio, M.; Donadio, S.; Maffioli, S. I.

Natural products are a sustainable resource for drug discovery, but their identification in complex mixtures remains a daunting task. We present an automated pipeline that compares, harmonizes and ranks the annotations of LC-HRMS data by different tools. When applied to 7,400 extracts derived from 6,566 strains belonging to 86 actinomycete genera, it yielded 150,000 molecules after processing over 50 million MS spectra. The web-based Molecules Gateway contains information on experimental and calculated data for these molecules, along with the metadata related to extracts and producer strains. We show how the Molecules Gateway can be used to rapidly identify rare known microbial products, unreported analogs of known families and not yet described metabolites. The Molecules Gateway, which complements available repositories of annotated MS data, is experimentally and computationally homogeneous, and thus amenable to global analyses, which show a large and untapped chemical diversity afforded by actinomycetes.