In many of the chemical reactions in living cells, enzymes act as catalysts in the conversion of certain compounds (substrates) into other compounds (products). Metabolic pathways are formed as the products of these reactions are used as the substrates of other reactions. Comparative analyses of the metabolic pathways among species provide important information on both evolution and potential pharmacological targets. Here, we propose a method to align the metabolic pathways based on similarities between chemical structures. To measure the degree of chemical similarity, we formalized a scoring system using the MACCS keys and the Tanimoto/Jaccard coefficients. To determine the effectiveness of our method, it was applied to analyses of metabolic pathways in Escherichia coli. The results revealed compound similarities between fructose and mannose biosynthesis and galactose biosynthesis pathways.

Comparative analyses of enzymatic reactions provide important information on both evolution and potential pharmacological targets. Previously, we focused on the structural formulae of compounds, and proposed a method to calculate enzymatic similarities based on these formulae. However, with the proposed method it is difficult to measure the reaction similarity when the formulae of the compounds constituting each reaction are completely different. The present study was performed to extract substructures that change within chemical compounds using the RPAIR data in KEGG. Two approaches were applied to measure the similarity between the extracted substructures: a fingerprint-based approach using the MACCS key and the Tanimoto/Jaccard coefficients; and the Topological Fragment Spectra-based approach that does not require any predefined list of substructures. Whether the similarity measures can detect similarity between enzymatic reactions was evaluated. Using one of the similarity measures, metabolic pathways in Escherichia coli were aligned to confirm the effectiveness of the method.

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