THEOBROMA: an aggregated open database of 1.13 million natural products with per-compound license auditing, three-tier classification, and stereochemistry-aware deduplication

Abstract

Natural products remain one of the most productive sources of pharmacologically active compounds for drug discovery. Open aggregators attribute licenses at database granularity, and the consequences of that choice have become tangible as the field grows. A recent relicensing event in one constituent source (the September 2024 transition of the Natural Products Atlas to CC BY-NC 4.0) demonstrates how database-level licensing propagates across an aggregate and motivates the per-compound audit framework presented here. The same peer cohort separately leaves classification provenance and stereoisomer-family relations coarser than either layer warrants. THEOBROMA, accessible at https://theobroma.l3s.uni-hannover.de, integrates 1 132 805 natural products from 29 open sources under a per-compound license audit that resolves each compound’s license tier across all attesting sources under a most-restrictive-wins rule. 896 242 compounds (79.12%) are identified under open-use licenses, and the per-source attestation chain, together with the resolved tier, is exposed through a dedicated audit endpoint and a query-time license filter. A three-tier classification labels all but 21 compounds by the provenance of the assignment (55.3% curated source labels, 18.2% NPClassifier tool assignments, 26.5% model-inferred). Deduplication at the full 27-character InChIKey retains 1 132 805 entries across 486 032 connectivity families, exposed via a dedicated /api/stereoisomers/<comp_id> endpoint and a radial-family display. Any result set renders directly onto a taxonomic cladogram of its source organisms, so compositional queries are answered in the interface rather than downstream. Per-compound license provenance is the primary differentiator, while classification stratification and stereoisomer-family exposure add finer-grained access to two related axes. Together, they support license-compatible virtual screening and isomer-specific bioactivity analysis at corpus scale. As an evolving open resource, THEOBROMA pairs continuous pipeline maintenance with interactive geographic, taxonomic, and chemical-space exploration.