For the target molecule set, molecules were filtered to be in the SMILES string length of 20 to 100. This was to maintain the target molecules from different datasets with fair synthetic difficulty. The aim was to include only 100,000 molecules to maintain reasonable computational costs. This was the case for the chemical and hybrid reactions pools. 100,000 molecules (excluding the molecular building blocks) were randomly selected from the molecule set as targets. Also, in each iteration of the optimisation, the target molecule set was reshuffled to increase randomness. However, since the biological dataset records only approximately 30,000 molecules, all molecules with SMILES string length of 20 to 100 (building blocks exclusive), i.e. 12,281 molecules were included as the set of target molecules to compute synthesis planning.