Computational metabolomics reveals overlooked chemodiversity of alkaloid scaffolds in the Piper genus

Plant specialized metabolites play key roles in physiological processes and ecological interactions. Identifying novel metabolites, as well as discovering known compounds in new species, is crucial for answering broader biological questions. The Piper genus (Piperaceae family) is known for its special alkaloids biochemistry, with more than 300 alkaloids (“piperamides”) reported to date. In a recent study [ 1 ], we investigated the alkaloid diversity of Piper fimbriulatum , a myrmecophytic plant native to Central America, using a metabolomics workflow that combines untargeted LC-MS analysis with a range of state-of-the-art computational tools. Specifically, we leveraged open MS/MS spectral libraries and metabolomics data repositories for metabolite annotation and guided isolation efforts toward structurally-novel compounds. As a result, we identified 22 alkaloids belonging to 5 different classes, and isolated one novel seco -benzylisoquinoline alkaloid carrying a linear quaternary amine moiety which we named fimbriulatumine . Notably, several of these alkaloids had never been reported in Piper plants, despite their extensive phytochemical investigation. To support this discovery, we sampled 12 additional Piper species and confirmed the presence of these alkaloids across the genus. Finally, we contextualized our findings within a broader biological framework by systematically mining literature reports of the identified alkaloid scaffolds across angiosperms. Specifically, we used the Wikidata knowledge base [ 2 ] for automated literature mining and mapped the results onto the angiosperm tree of life [ 3 ] ([ Fig. 1 ]). Our findings expand the known Piperaceae alkaloid diversity and demonstrate the value of revisiting well-studied plant families using modern computational metabolomics. Fig. 1 Angiosperm tree of life [ 3 ] mapped with literature reports, mined from Wikidata [ 2 ], of the alkaloid scaffolds discovered in the study [ 1 ]. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany