MicrobeRX: a tool for enzymatic-reaction-based metabolite prediction in the gut microbiome.

Background: The gut microbiome functions as a metabolic organ, producing numerous enzymes that influence host health; however, their substrates and metabolites remain largely unknown.

Results: We present MicrobeRX, an enzyme-based metabolite prediction tool that employs 5487 human reactions and 4030 unique microbial reactions from 6286 genome-scale models, as well as 3650 drug metabolic reactions from the DrugBank database (v.5.1.12). MicrobeRX includes additional analysis modules for metabolite visualization and enzymatic and taxonomic analyses. When we applied MicrobeRX to 1083 orally administered drugs that have been approved in at least one jurisdiction at some point in time (DrugBank), it predicted metabolites with physicochemical properties and structures similar to metabolites found in biosamples (from MiMeDB). It also outperformed another existing metabolite prediction tool (BioTransformer 3.0) in terms of predictive potential, molecular diversity, reduction of redundant predictions, and enzyme annotation.

Conclusions: Our analysis revealed both unique and overlapping metabolic capabilities in human and microbial metabolism and chemo- and taxa-specific microbial biotransformations. MicrobeRX bridges the genomic and chemical spaces of the gut microbiome, making it a valuable tool for unlocking the chemical potential of the gut microbiome in human health, the food and pharmaceutical industries, and environmental safety. Video Abstract.