XMetDB: an open access database for xenobiotic metabolism

Abstract

Xenobiotic metabolism is an active research topic but the limited amount of openly available high-quality biotransformation data constrains predictive modeling. Current database often default to commonly available information: which enzyme metabolizes a compound, but neither experimental conditions nor the atoms that undergo metabolization are captured. We present XMetDB, an open access database for drugs and other xenobiotics and their respective metabolites. The database contains chemical structures of xenobiotic biotransformations with substrate atoms annotated as reaction centra, the resulting product formed, and the catalyzing enzyme, type of experiment, and literature references. Associated with the database is a web interface for the submission and retrieval of experimental metabolite data for drugs and other xenobiotics in various formats, and a web API for programmatic access is also available. The database is open for data deposition, and a curation scheme is in place for quality control. An extensive guide on how to enter experimental data into is available from the XMetDB wiki. XMetDB formalizes how biotransformation data should be reported, and the openly available systematically labeled data is a big step forward towards better models for predictive metabolism.

Keywords: Cytochrome; Database; Metabolism; P450; Xenobiotic.

Fig. 1

Browsing observations in XMetDB. When browsing all or a subset of observations, the table shows the chemical structures of substrate and product together with other data and metadata

Fig. 2

Browsing enzymes in XMetDB. When browsing all or a subset of enzymes, the table shows the Code, Name, UniProt ID, and optionally allele for each entry

Fig. 3

Examples of how biotransformations should be reported. This example shows the atoms defined as reaction centra indicated in blue. Top Hydroxylation of aromatic carbons. Bottom Hydroxylation of aromatic carbons coupled with halogen migration