All balanced reactions were then atom mapped by applying the publicly available reaction rules from Ref. 60 (termed "Broadbelt rule set" in the following) and tracking each atom throughout rule application. Since the Broadbelt rule set does not contain rules for reactions only affecting stereochemistry (e.g. cis/trans isomerases or racemases), we mapped reactions with the same achiral reactants and products directly without rule application. All other reactions were mapped through rule application. We first aimed to reproduce the recorded product via a single application of each rule. If multiple rules produced the correct product, leading to different atom mappings, only the rule changing the fewest number of atoms and bonds, as well as being most frequently applicable was used. To speed up rule application, we ordered the rules from Ref. 60 based on their frequency of applicability to all BRENDA entries. In Fig. , this procedure yielded the mapped reaction Fig. Oxidation of 1,2-butanediol as an example of a multi-step reaction requiring rule application at two sites. For readability, atom maps were omitted. The stoichiometry of the reaction was corrected (note the missing "2" in the original reaction text). The multi-step reaction can be split into four distinct single-step reactions, where either the C1 or C2 can be oxidized first.