For example, the Rhea database includes data on a considerable number of tailoring enzymes involved in natural product biosynthesis . Rhea describes enzymatic reactions as a stoichiometrically balanced set of involved reactants, using the ChEBI ontology to reference the participating small molecules . Several other databases, such as the UniProtKB or the Reactome Pathway Database, use Rhea as reference for enzyme chemistry . While Rhea focuses on reactions involving specific reactants, it can also use generic classes from the ChEBI ontology to describe reactions where exact substrates and products are not known. However, in NP biosynthetic pathways, even the exact order of reactions is usually not known, making it challenging to arrive at a curated set of reactants that sufficiently and specifically describe the site of metabolism without knowledge of the full structures of substrates and products. Further, the reactions of a promiscuous enzyme or iterative reactions on a core scaffold must be described as a discrete list of all possible reactant pairs. Therefore, NP biosynthesis-typical cascades of enzymatic reactions with partially defined substrate-product pairs are currently difficult to describe by Rhea and would benefit from a dedicated resource that is tightly connected with NP-specific resources on genomic data and chemical structures.