Abstract
There is a tendency that a unit of enzyme genes in an operon‐like structure in the prokaryotic genome encodes enzymes that catalyze a series of consecutive reactions in a metabolic pathway. Our recent analysis shows that this and other genomic units correspond to chemical units reflecting chemical logic of organic reactions. From all known metabolic pathways in the KEGG database we identified chemical units, called reaction modules, as the conserved sequences of chemical structure transformation patterns of small molecules. The extracted patterns suggest co‐evolution of genomic units and chemical units. While the core of the metabolic network may have evolved with mechanisms involving individual enzymes and reactions, its extension may have been driven by modular units of enzymes and reactions.