MetabFlow: a comprehensive metabolic map for exogenous natural products

Exogenous natural products (NPs) undergo complex metabolic transformations both in vivo and in vitro, generating structurally diverse metabolites. Due to the involvement of host enzymes and gut microbiota, as well as the structural complexity of NPs themselves, their metabolic processes exhibit unique characteristics. However, existing metabolic transformation information remains fragmented, limiting systematic understanding of their metabolic mechanisms. To address this gap, MetabFlow (https://bddg.hznu.edu.cn/metabflow/), a comprehensive database dedicated to the metabolism of exogenous NPs, was developed. MetabFlow is distinguished by: (a) systematic integration of 7294 curated metabolic reactions covering both in vivo and in vitro transformations, providing a complete knowledge map of exogenous NP metabolism; (b) unique integration of enzyme-catalyzed and microbiota-mediated reactions, highlighting the distinctive metabolic features of NPs; (c) establishment of a structured metabolic network by constructing upstream-downstream reaction relationships, elucidating how exogenous NPs evolve across different metabolic pathways; (d) inclusion of approximately 3200 compounds not indexed in mainstream databases, with detailed structural information, annotations, and complete metabolic profiles. MetabFlow is designed to support research in NP metabolism, drug discovery, and related fields.