Reaction SMARTS can be generated in various ways, most conveniently by simply drawing them using a conventional chemistry drawing program. This allows for intuitive creation of reaction SMARTS, without requiring specialist knowledge (e.g. IUPAC nomenclature). We intend MITE to accept three types of reaction SMARTS: Daylight SMIRKS (31), conventional reaction SMARTS (as used by RDKit Q3 2023 release (32)), or Chemaxon SMARTS (CXSMARTS) . The latter introduces optional metadata to the reaction, which allows the use of more sophisticated ways of reaction representation, such as the addition of position variation bonds or frequency variation (see Supplementary Methods ). These additional features can be used to express reactions more concisely than simple enumeration of all possible substrate-product pairs. For example, if a halogenase can introduce a chlorine in the 5, 6, or 7 position of a tryptophan, this can be represented with a position variation bond instead of three different reaction SMARTS. Similarly, if an enzyme would accept aliphatic carbon chains of different lengths, the variance in substrates can be summarized with a frequency variation. However, use of CXSMARTS is not mandatory, and users may decide to represent all possible substrate pairs explicitly as conventional reaction SMARTS. Since a reaction SMARTS can be represented also only by substructures of the substrate(s) or product(s) that are involved in the reaction, it does not necessarily encode complete chemical structures. However, availability of the authentic substrate(s) and product(s) of the reaction as full chemical structures is useful for illustration and validation purposes.