MetabFlow: a comprehensive metabolic map for exogenous natural products

Area of Science:

• Pharmacology and Natural Product Chemistry
• Metabolomics and Bioinformatics

Background:

• Exogenous natural products (NPs) undergo intricate metabolic transformations via host enzymes and gut microbiota, yielding diverse metabolites.
• Current understanding of NP metabolic mechanisms is fragmented due to the complexity of NPs and their metabolic pathways.
• Existing data on NP metabolism is insufficient for systematic analysis and knowledge integration.

Purpose of the Study:

• To develop a comprehensive database, MetabFlow, for systematically analyzing the metabolism of exogenous natural products.
• To create a unified knowledge map of in vivo and in vitro NP metabolic transformations.
• To support research in natural product metabolism, drug discovery, and related fields.

Main Methods:

• Systematic integration of 7294 curated metabolic reactions for in vivo and in vitro NP transformations.
• Combined analysis of enzyme-catalyzed and microbiota-mediated reactions to capture unique NP metabolic features.
• Construction of a structured metabolic network detailing upstream-downstream reaction relationships.
• Inclusion of approximately 3200 compounds absent in mainstream databases, with comprehensive annotations.

Main Results:

• Established a complete knowledge map of exogenous NP metabolism through integrated reaction data.
• Highlighted distinctive metabolic features of NPs by combining host enzyme and gut microbiota pathways.
• Elucidated the evolution of exogenous NPs across different metabolic pathways via a structured network.
• Provided detailed information for novel compounds, enhancing the scope of NP metabolism studies.

Conclusions:

• MetabFlow offers a comprehensive resource for understanding exogenous NP metabolism.
• The database facilitates systematic research into NP metabolic mechanisms and pathways.
• MetabFlow is a valuable tool for advancing drug discovery and related scientific endeavors.