The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases

Abstract

The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible database describing metabolic pathways and enzymes from all domains of life. MetaCyc pathways are experimentally determined, mostly small-molecule metabolic pathways and are curated from the primary scientific literature. MetaCyc contains >2100 pathways derived from >37,000 publications, and is the largest curated collection of metabolic pathways currently available. BioCyc (BioCyc.org) is a collection of >3000 organism-specific Pathway/Genome Databases (PGDBs), each containing the full genome and predicted metabolic network of one organism, including metabolites, enzymes, reactions, metabolic pathways, predicted operons, transport systems and pathway-hole fillers. Additions to BioCyc over the past 2 years include YeastCyc, a PGDB for Saccharomyces cerevisiae, and 891 new genomes from the Human Microbiome Project. The BioCyc Web site offers a variety of tools for querying and analysis of PGDBs, including Omics Viewers and tools for comparative analysis. New developments include atom mappings in reactions, a new representation of glycan degradation pathways, improved compound structure display, better coverage of enzyme kinetic data, enhancements of the Web Groups functionality, improvements to the Omics viewers, a new representation of the Enzyme Commission system and, for the desktop version of the software, the ability to save display states.

Figure 1.

The new glycan degradation pathways use symbolic representation to illustrate the structures of complex glycan molecules. Colored arrows show the sites that are cleaved by enzymes and provide hyperlinks to those enzymes. The final products produced by the combined degradation of the polymer by all enzymes are listed on the right side of the diagram.

Figure 2.

This figure illustrates some of the different types of enzymatic kinetic data that can be captured and presented by Pathway Tools. The software lets the curator enter the data using the units reported in a paper, and converts them automatically to the standard units. When possible, the catalytic efficiency is computed automatically and included in the table. Temperature and pH optima can be captured differently for the two directions of a reversible reaction.

Figure 3.

EC numbers are now database objects that have their own pages. An EC-Number page includes all of the information defined by the EC, and additional information that includes a list of unofficial reactions (see text for details) and a list of enzymes determined by the software to fit the definition of the EC number.

Figure 4.

The new right-sidebar on BioCyc web pages contains operations that are specific to the currently displayed page. The operations and links available on the sidebar change depending on the type of object that is currently displayed. In this example, the operations and links are relevant to an Escherichia coli gene/protein page. Operations and links that are not specific to a particular object type are available from the menu bar at the top of the page and do not change.

Figure 5.

The Cellular Omics Viewer allows the user to paint omics data over the cellular Overview. New functionality enables the display of per-node omics data in a pop-up window as a column chart, an x-y plot or a heat map. The pop-ups can also be generated to show all the data for a given pathway. This figure also shows the pop-up that appears on right-clicking a reaction.

Figure 6.

Pathway diagram customization is available via the web interface, and lets the user control many aspects of the pathway diagram. A new option allows painting user-supplied Omics data directly to the pathway. The modified diagram can be exported to a pdf or postscript format file for incorporation in presentations or manuscripts.