The meta-fission pathway for homoprotocatechuic acid (HPC) catabolism is chemically analogous to the oxidative meta-fission pathway for catechol degradation and so provides an opportunity to investigate how the enzymes of chemically similar, but specific, pathways might have arisen. Two more genes of the HPC pathway from Escherichia coli C, hpcC, encoding 5-carboxymethyl-2-hydroxymuconic acid semialdehyde (CHMS) dehydrogenase, and hpcG, encoding 2-oxohept-3-ene-1,7-dioic acid (OHED) hydratase, have now been sequenced to aid this analysis. The CHMS dehydrogenase showed 40% amino acid (aa) sequence identity with the corresponding enzyme of the catechol pathway, and the OHED hydratase showed 36% aa sequence identity with the catechol pathway hydratase. The CHMS dehydrogenase is a member of the aldehyde dehydrogenase superfamily that includes enzymes from animal, plant and microbial sources. Since it appears that the dioxygenase, isomerase and decarboxylase enzymes of the two pathways are not closely related, it is proposed that the two sets of enzymes have arisen separately, but with the muconic acid semialdehyde dehydrogenases and the hydratases being recruited, respectively, from the same ancestral sources.