The MetaCyc database (http://metacyc.org/) provides a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains more than 1800 pathways derived from more than 30 000 publications, and is the largest curated collection of metabolic pathways currently available. Most reactions in MetaCyc pathways are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes and literature citations. BioCyc (http://biocyc.org/) is a collection of more than 1700 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference database, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs contain additional features, including predicted operons, transport systems and pathway-hole fillers. The BioCyc website and Pathway Tools software offer many tools for querying and analysis of PGDBs, including Omics Viewers and comparative analysis. New developments include a zoomable web interface for diagrams; flux-balance analysis model generation from PGDBs; web services; and a new tool called Web Groups.

EcoCyc (http://EcoCyc.org) is a model organism database built on the genome sequence of Escherichia coli K-12 MG1655. Expert manual curation of the functions of individual E. coli gene products in EcoCyc has been based on information found in the experimental literature for E. coli K-12-derived strains. Updates to EcoCyc content continue to improve the comprehensive picture of E. coli biology. The utility of EcoCyc is enhanced by new tools available on the EcoCyc web site, and the development of EcoCyc as a teaching tool is increasing the impact of the knowledge collected in EcoCyc.

BackgroundThe MetaCyc and KEGG projects have developed large metabolic pathway databases that are used for a variety of applications including genome analysis and metabolic engineering. We present a comparison of the compound, reaction, and pathway content of MetaCyc version 16.0 and a KEGG version downloaded on Feb-27-2012 to increase understanding of their relative sizes, their degree of overlap, and their scope. To assess their overlap, we must know the correspondences between compounds, reactions, and pathways in MetaCyc, and those in KEGG. We devoted significant effort to computational and manual matching of these entities, and we evaluated the accuracy of the correspondences.ResultsKEGG contains 179 module pathways versus 1,846 base pathways in MetaCyc; KEGG contains 237 map pathways versus 296 super pathways in MetaCyc. KEGG pathways contain 3.3 times as many reactions on average as do MetaCyc pathways, and the databases employ different conceptualizations of metabolic pathways. KEGG contains 8,692 reactions versus 10,262 for MetaCyc. 6,174 KEGG reactions are components of KEGG pathways versus 6,348 for MetaCyc. KEGG contains 16,586 compounds versus 11,991 for MetaCyc. 6,912 KEGG compounds act as substrates in KEGG reactions versus 8,891 for MetaCyc. MetaCyc contains a broader set of database attributes than does KEGG, such as relationships from a compound to enzymes that it regulates, identification of spontaneous reactions, and the expected taxonomic range of metabolic pathways. MetaCyc contains many pathways not found in KEGG, from plants, fungi, metazoa, and actinobacteria; KEGG contains pathways not found in MetaCyc, for xenobiotic degradation, glycan metabolism, and metabolism of terpenoids and polyketides. MetaCyc contains fewer unbalanced reactions, which facilitates metabolic modeling such as using flux-balance analysis. MetaCyc includes generic reactions that may be instantiated computationally.ConclusionsKEGG contains significantly more compounds than does MetaCyc, whereas MetaCyc contains significantly more reactions and pathways than does KEGG, in particular KEGG modules are quite incomplete. The number of reactions occurring in pathways in the two DBs are quite similar.