• Fermentation metabolic enzymes and pathways, such as the lactate dehydrogenase enzyme, and various alternative NAD+ regeneration pathways, including the 2,3-butanediol and mannitol biosynthesis pathways
• Fifteen transporters including PTS systems responsible for the uptake of sugars, ABC family transporters that mediate uptake of various peptides, amino acids and osmoprotectants, and several multidrug efflux transporters
• Enzymes and reactions of peptidoglycan metabolism, cell wall polysaccharide production, and menaquinone biosynthesis
• Enzymes involved in proton motive force (PMF)-generation via electron transport chain that functions when L. lactis is grown aerobically

• Addition of experimental evidence codes to 16 gene products
• Addition of one new metabolic pathway, S-(2-succinyl)-L-cysteine degradation

• L-aspartate degradation II (aerobic)
• L-aspartate degradation III (anaerobic)

• N-acetylneuraminate and N-acetylmannosamine degradation I
• uracil degradation III
• chitobiose degradation

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

Release Notes for BioCyc Version 25.0

Released on May 20, 2021.

Version 25.0 is a major release that includes updates to the BioCyc Web site and downloadable data files, and a new version of the downloadable Pathway Tools software.

Version 25.0 of BioCyc contains 17,835 Pathway/Genome Databases.

Chrome and Firefox are the recommended web browsers for BioCyc, followed by Safari and Edge. Web browsers are incompatible, they can treat the same web page differently.
If you are having difficulties with the new BioCyc release, try doing a hard reload (hold down the Shift key and click the Reload button on your browser); deleting cookies can also help.

1. Improvements to BioCyc Databases

Updates to BioCyc Databases

• 2427 BioCyc databases were regenerated from the newest RefSeq annotations and the newest version of MetaCyc.
• Updates to Chlamydia trachomatis D/UW-3/CX include improvement of the central metabolic pathways, additional curation of lipoate metabolic genes, protein complexes and reactions, and additional representations of transporters and their reactions.
• Acinetobacter baumannii AB5075-UW was upgraded from a Tier 3 to a tier 2 PGDB primarily through propagation of orthologous genes from the closely related Acinetobacter baumannii ATCC 17978 PGDB. Both PGDBs were updated further through curation of genes associated with the GacSA two-component regulatory system and the phenylacetate degradation genes, transcriptional unit and pathway, as well as the type II secretion system.
• BsubCyc upgrades: For this release, we have curated 151 gene products that encode transmembrane transporters or transporter components. Curation included the creation of 14 new transporter protein complexes. 17 additional, not transport-related proteins were fully curated. BsubCyc currently contains references to 223 papers published in 2020 and 58 papers published in 2021.
  • We have added a new signal transduction pathway for the PsdSR two-component signal transduction system.

Updates to MetaCyc Version 25.0

We have added 85 new pathways to MetaCyc since the last release and revised 15 pathways by modifying pathway diagrams, adding commentary, or updating enzyme and gene information. We also added two superpathways, for a total of 102 new and updated pathways.

Some highlights of the new additions to MetaCyc include:

The lipopolysaccharides (LPS) are composed of three components – lipid A, the core oligosaccharide, and the O antigen. We have added several pathways that describe the biosynthesis of lipid A and the core oligosaccharides of Brucella species and Porphyromonas gingivalis, and added many pathways for the biosynthesis of O antigens. We now have full coverage of the O antigens produced by Salmonella species, by many Escherichia coli serotypes, and by Brucella abortus, Porphyromonas gingivalis, and some strains of Shigella boydii.

We created a new pathway for the biosynthesis of colanic acid, an exopolysaccharide secreted by E. coli and a number of other Enterobacteriaceae. We also revised existing pathways for the biosynthesis of succinoglycan and the enterobacterial common antigen (ECA).

Arsenic is a natural component of the earth’s crust and is widely distributed throughout the environment in the air, water and land. It exists most commonly in the (III) and (V) oxidation states, and many compounds of both forms are highly toxic. All organisms have developed defense mechanisms to cope with arsenic compounds. In this release we performed an extensive revision of our coverage of arsenic compound metabolism. We now have an up-to-date coverage of all known arsenic-related enzymes in bacteria, yeast, plants and animals.

EC 7.1.1.10, ferredoxin—quinone oxidoreductase (H+-translocating) is a key enzyme in the electron transfer chain of cyanobacteria and plastids that until recently has been mischaracterized. The enzyme couples electron transport from ferredoxin to plastoquinone with proton pumping from the cytoplasm to the thylakoid lumen, and participates in cyclic electron flow, retuning electrons generated by photosystem I to the plastoquinone pool, thus bypassing the generation of reducing power. Based on the new functional characterization of the enzyme we have revised several cyanobacterial electron transport pathways and created a new pathway to describe cyclic electron flow.

A new pathway describes the biosynthesis of 11-oxygenated C19 steroids (11-oxyandrogens). These steroids have long been recognized as major androgens in teleost fishes. However, more recently it has been discovered that they are also produced in humans and play an important role in several disorders such as congenital adrenal hyperplasia (CAH), polycystic ovary syndrome (PCOS), and premature adrenarche.

Updates to EcoCyc Version 25.0

The EcoCyc data have been curated from 40,472 publications.

Significant updates to EcoCyc include:

• Enzyme I (EI) of the bacterial phosphotransferase system is known to form clusters that localize to the cell poles. Szoke et al. now report that EI is recruited to the poles by a formerly uncharacterized protein, TmaR. Polar localization of both proteins is dependent on tyrosine phosphorylation and TmaR-mediated polar sequestration, and release of EI serves to regulate sugar metabolism.

• We added new conformations for some transcription factors, including dimers for the transcriptions factors FrlR (Graf von Armansperg et al.) and DgoR (Arya et al.) as well as the new inactive conformations FrlR-fructoselysine-6-phosphate (Graf von Armansperg et al.) and MprA-salicylate (Arshad et al.).

• Summaries for four sigma factors and 29 transcription factors were updated.

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

2. New in the BioCyc Website

• Website Design Refresh: We have updated the BioCyc website to give it a more modern look and to increase its accessibility to new users.

• Multi-PGDB Searches: Several of the searches available under Tools → Search now enable searches across multiple organism databases (up to 70). For example, this option enables searching across multiple strains or members of a microbial community to find which organisms contain a given gene, metabolite, or pathway. All the search and filtering options applicable to that search are supported. The searches include
  • Search Genes, Protein or RNA
  • Search Compounds
  • Search Reactions
  • Search Pathways

• Multiple Sequence Alignment: The alignment tool at Tools → Analysis → Multiple Sequence Alignment now supports alignment of arbitrary nucleotide regions of a replicon, and aligning user-provided sequences in addition to sequences from BioCyc databases.

• Comparative Analysis: Many improvements have been made to the comparative tools under Tools → Analysis → Comparative Analysis:
  • The tools are significantly faster.
  • The organism comparison provides new comparisons of phenotype metadata, collection metadata, and annotation metadata
  • The reactions comparison now identifies both shared and unique reactions between organisms
  • Comparisons of biosynthetic pathways now provide both a pathway view and a metabolite view that more clearly identifies which metabolites can be synthesized -- see example
  • The compounds comparison now identifies both shared and unique metabolites between organisms

Release Notes for BioCyc Version 24.5

Released on January 7, 2021.

Version 24.5 is a major release that includes updates to the BioCyc Web site and downloadable data files, and a new version of the downloadable Pathway Tools software.

Version 24.5 of BioCyc contains 18,030 Pathway/Genome Databases.

1. Improvements to BioCyc Databases

Updates to Other databases

• 1654 databases were regenerated from the newest RefSeq annotations and the newest version of MetaCyc. No new databases were added in this release.
• BsubCyc upgrades: BsubCyc has added references to new publications to 130 genes. Nine of these genes were also renamed in the cited publications. BsubCyc cites 197 papers published in 2020 and 233 published in 2019. GO terms with experimental evidence were added to 44 gene products, for a total of 797 gene products annotated with experimental GO terms.

Chlamydia trachomatis D/UW-3/CX Upgraded to Tier 2 Curated Database

• Rerunning the enzymatic reaction and pathway prediction algorithms followed by curator review, resulting in an increase of more than 51 enzymatic reactions and 7 pathways to a total of 571 and 83, respectively.
• Creation of 10 new protein complexes
• Literature-based curation from 35 publications, resulting in experimental evidence for 84 additional genes and proteins and significant improvement in the central metabolic pathways.
• 2685 protein features were imported from UniProt

BioCyc contains databases for 127 sequenced Chlamydia genomes, 15 of which are representative or reference genomes.

Updates to MetaCyc Version 24.5

We have added and/or updated 15 pathways in MetaCyc since the last release.

Significant updates to MetaCyc include:

• During this release period we curated pathways for the biosynthesis of seven of the most common O antigens of Salmonella, which are found in members of groups A, B, C2, D1, D2, D3 and E.
• Added a pathway for the generation of 5α-dihydrotestosterone (DHT) that does not involve testosterone.
• Added a pathway for production of cholesterol in red alga (e.g. Chondrus crispus) that differs from that in plants.
• Added a novel dTMP biosynthetic pathway unique to mitochondria.

Updates to EcoCyc Version 24.5

The EcoCyc data have been curated from 39,932 publications.

Significant updates to EcoCyc include:

• YedR has been characterized as a non-essential cell division protein and renamed to DrpB
• Updated the summaries and regulatory interactions of most small RNAs encoded by E. coli K-12
• Added 675 protein localizations from PSORT and Gravy

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

2. New in the Biocyc Website

• Metabolic Network Explorer: The new Metabolic Network Explorer facilitates the interactive exploration of the metabolic network around a set of connected compounds of interest. To access this tool, go to Metabolism → Metabolic Network Explorer and enter a starting metabolite. You can then build up a linear reaction path by adding successive reactions forward or backward from the current path. For each metabolite along the central path, lists of precursor and successor metabolites provide information about other possible connections to that metabolite, and allow the user to extend or change the central path to follow one of those connections. Various customizations are supported.

• Regulatory Overview: We've upgraded the regulatory network browser (Regulatory Overview) to utilize HTML5 canvas graphical rendering via our Webgraphics package, yielding better quality graphics and faster zooming. We also have incorporated changes that enable the user to display successive levels of regulation one level at a time, and to print to a file either the entire regulatory network, or the network regulated by a single gene.

• Circular Genome Viewer: A new circular genome viewer tool provides a global view of the organization of one or more chromosomes as a set of concentric circles (tracks) containing features (genes, promoters, binding-sites, other extragenic sites) of interest. A given track can be customized to show and/or highlight features that match specified criteria. For example, a track can be filtered to only show RNA genes, or transporters, or genes from an uploaded file. Alternatively, a track might show all genes, but highlight those involved in certain pathway classes or annotated to specified GO terms. The circular genome viewer can also be used to compare chromosomes from multiple closely related strains, such that highlights can be applied to orthologs across all strains. See Genome → Circular Genome Viewer.

• Genome Overview: Genome Overview already was using Webgraphics for rendering, but we added the ability to highlight genes, either by the gene name or identifier, or by highlighting those genes whose name has a shared substring.

• Multiple Sequence Alignment: We've updated Multiple Sequence Alignment to utilize Clustal Ω for computing the alignments and to utilize MSAViewer for the visualization of the alignments.

• Comparative Analysis: The organism comparison report now compares organism metadata. The reaction comparison report now includes those reactions unique to each organism.

Release Notes for BioCyc Version 24.1

Released on September 8, 2020.

Version 24.1 is a minor release that includes updates to the BioCyc website and downloadable data files.

Version 24.1 of BioCyc contains 18,023 Pathway/Genome Databases, of which 1,247 are new genomes and 680 of the PGDBs were re-generated. 1,927 of the PGDBs are for NCBI representative genomes.

1. Improvements to BioCyc Databases

Integration of Phenotype Microarray Datasets

• Acinetobacter baumannii ATCC 17978
• Acinetobacter baumannii AYE
• Acinetobacter baumannii D1279779
• Acinetobacter baumannii ACICU
• Pectobacterium parmentieri SCC3193
• Pseudoalteromonas haloplanktis AC125

Curation of Acinetobacter baumannii ATCC 17978 Database

• Rerunning the pathway prediction algorithm followed by curator review, resulting in an increase of more than 40 pathways to a total of 253.
• Literature-based curation from more than 80 publications, resulting in experimental evidence for 178 additional genes and proteins and significant improvement in the corresponding enzymatic and transport reactions.
• The number of protein complexes and transporters increased by 38 and 25, respectively.
• 4450 protein features were imported from UniProt
• A Phenotype Microarray dataset was imported

BioCyc contains databases for 265 sequenced Acinetobacter genomes.

Updates to Lactobacillus rhamnosus GG Database

• Propagation of cumulative changes in MetaCyc to synchronize the two databases.
• Removal of incorrectly predicted enzymatic reaction, transport activities, and metabolic pathways.
• Addition of 12 new pathways: exopolysaccharide biosynthesis, NADH to cytochrome d electron transfer, NADP biosynthesis, polyphosphate metabolism, bile acids deconjugation, 2-deoxy-D-glucose 6-phosphate degradation, arsenate detoxification III (thioredoxin), alanine racemization, 2-deoxy-D-ribose degradation I, 5-oxo-L-proline metabolism, tRNA-uridine 2-thiolation and selenation, and lipoprotein posttranslational modification.
• Creation of more protein complexes (the number of protein complexes increased from 37 to 85, including large complexes such as the ribosome).
• Literature-based curation of PubMed publications that include specific metabolic information about the organism. Among the newly curated proteins are alpha-L-fucosidases A, B and C; all enzymes involved in biosynthesis of the main exopolysaccharide (WelEFGHIJ); the proteins that make up the SpaCBA and spaFED pili and their sortases; mucus-binding factor (Mbf); adhesin (MabA); lectin-like proteins 1 and 2 (Llp1 and Llp2); major secreted proteins 1 and 2 (Msp1 and Msp2, also known as P75 and P40); NADH oxidase; lactate dehydrogenases LdhD1 and LdhD2; glutamate dehydrogenase GdhA; glutathione peroxidase Gpx; glutathione reductase GshR; glutathione ABC transporter; L-fucose/H+ symporter FucP; fucose isomerase FucI; and bacteriocin.

Updates to MetaCyc Version 24.1

MetaCyc now contains 2,847 metabolic pathways -- we have added or significantly revised 39 pathways in this release.

MetaCyc contains the equivalent of 10,111 textbook-pages of mini-review summaries.

Areas of MetaCyc curation for this release include new pathways in the following areas:

• Fatty acid metabolism
• Stickland reactions
• Cofactor biosynthesis
• Sulfur compound metabolism
• Biosynthetic bacterial pathways
• Cyanobacterial pathways
• Plant pathways
• Fungal pathways

MetaCyc Sequence Files: The sequence files used by the PathoLogic pathway hole-filler have been enhanced to include ids and sequences from ENTREZ in addition to UniProt. These files identify proteins in UniProt and ENTREZ that are associated with different enzyme activities. These files were previously called uniprot-seq-ids.dat and uniprot-seq-ids.seq. The new files, which are available in the MetaCyc flat-file distribution, are now called the following. All of the files are formatted as Lisp lists, actually as a list of lists. Each Lisp list is a series of items enclosed in parentheses.

• protein-seq-ids-reduced-70.dat -- A list of lists, where each list contains a MetaCyc reaction id, an EC number, and one or more protein identifiers with a prefix of either UNIPROT for uniprot identifiers or PID for ENTREZ-derived identifiers. In this file, sequences with more than 70% blast similarity to previously processed sequences have been removed as "redundant." The .seq file is supplied for the reduced set only.

• protein-seq-ids-reduced-70.seq -- A list of lists, with each list consisting of a protein id with database prefix, followed by the amino acid sequence of the protein specified by the id. Corresponds to the preceding .dat file.

• protein-seq-ids-unreduced.dat -- Similar to protein-seq-ids-reduced-70.dat, but no removal of similar sequences has been performed.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

Updates to Other E. coli PGDBs in BioCyc 24.1

To improve the other E. coli PGDBs in BioCyc (meaning those PGDBs describing strains other than K-12 MG1655), we propagated gene and protein annotations from EcoCyc to the 480 other E. coli PGDBs in BioCyc. On average, each of those PGDBs received updates to 2535 gene or proteins. The information we propagated included gene and protein names, protein complex assignments, and the reactions assigned to each protein. Propagation was performed from a gene or protein in EcoCyc only if it had experimental support, and only if the existing annotations for the target gene or protein did not have experimental evidence. The target gene/protein is a computed ortholog of the source gene/protein. The propagation event was recorded in a "history entry" for the target gene/protein that is displayed on the gene/protein page and explains what information was propagated.

Updates to EcoCyc Version 24.1

The EcoCyc data have been curated from 39,000 publications.

• New functions were added to the membrane proteins YihG, characterized as a lysophosphatidic acid acyltransferase which affects swimming motility, and DigH (formerly YddW), a glycosyl hydrolase that cleaves denuded peptidoglycan during cell division.

• Bradley et al. have reported that YcaQ is an alkylpurine DNA glycosylase involved in the repair of interstrand DNA crosslinks.

• Kentache et al. and Bell et al. (and references therein) have elucidated the function of NanY in E. coli. The enzyme is involved in the utilization of dehydrated forms of N-acetylneuraminate as a source of carbon and energy. The gut bacterium Ruminococcus gnavus is able to convert host-derived mucins to 2,7-anhydro-α-N-acetylneuraminate, which appears to be imported and utilized by E. coli.

• A total of 1009 new regulatory interactions from high throughput experiments have been uploaded for the following transcription factors:
  • ArcA from Federowicz et al.
  • ArgR from Caldara et al. and Cho et al.
  • CsiR from Aquino et al.
  • FNR from Federowicz et al.
  • Lrp from Cho et al. and Kroner et al.
  • Nac from Aquino et al.
  • OmpR from Shimada et al.

• Promoters were modified to be consistent with the definition in Mejia-Almonte et al.. When RNA polymerase initiates transcription using a different sigma factor, even if using the same transcription start site (TSS), we now consider it a different promoter. As a consequence, we generated new promoters (and consequently new transcription units), each with a different sigma factor, that share the same TSS.

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

Release Notes for BioCyc Version 24.0

Released on May 14, 2020.

Version 24.0 is a major release that includes updates to the BioCyc Web site and downloadable data files, and a new version of the downloadable Pathway Tools software.

Version 24.0 of BioCyc contains 16,817 Pathway/Genome Databases.

1. Improvements to BioCyc Databases

• ~120 new databases are included in this release, mostly for NCBI reference genomes. To find the reference genomes, click "change organism database" at the top-right of the BioCyc home page, then click the "Organism Filter" menu in the upper right of the pop-up window.

• ~2,000 databases were regenerated from the newest RefSeq annotations and the newest version of MetaCyc

• A number of duplicate or low-quality databases were removed

• Mycobacterium tuberculosis H37Rv
  • A curation update was performed to include new gene functions and pathways from recent publications

• BioCyc contains three new, highly curated cyanobacterial Pathway/Genome Databases, in addition to one previously existing curated cyanobacterial database (for Synechococcus elongatus PCC 7942). Each database integrates a variety of information including the genome, metabolic pathways, operons, protein features, Gene Ontology terms, and orthologs. Each of these databases received extensive literature-based curation to correct annotation errors and to integrate information about experimentally determined pathways and gene functions. For more information on these databases, click here. The curated databases are:
  • Synechococcus sp. WH 8102 (new)
  • Prochlorococcus marinus CCMP1375 (new)
  • Prochlorococcus marinus subsp. pastoris (strain CCMP1986) (new)
  • Synechococcus elongatus PCC 7942 (updated)

New in MetaCyc Version 24.0

MetaCyc now contains 2,801 metabolic pathways from all domains of life. MetaCyc contains the equivalent of 9,790 textbook-pages of mini-review summaries.

We have added and/or updated 49 pathways in MetaCyc since the last release.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

New in EcoCyc Version 24.0

• We imported five large acetylation datasets into EcoCyc in this release.
• In the 1970s, an enzyme that catalyzed the transfer of the aminocarboxypropyl group from S-adenosylmethionine to the N3 position of uridine within tRNAs was identified. However, the identity of the gene encoding this enzyme remained unknown. Recently, Takakura et al. and Meyer et al. both identified tapT (formerly known as yfiP) as the responsible gene.

• We have updated curation of the AlkB nucleic acid repair protein following a study by Reichle et al. identifying 2-thiocytidine-modified tRNA as a target of methylation damage and demonstrating AlkB-mediated repair.

• The representation of cytochrome bd-1 oxidase has been updated to include a previously unknown accessory subunit, CydH, identified in the cryo-EM structure reported by Safarian et al..

• Data from four high-throughput analyses, including RNA quadruplex structures (Shao et al.), RNA polymerase-binding RNA aptamers affecting gene expression (Magan et al.), the kinetics of gene expression after σ^E induction (Lacoux et al.), and the location of mRNAs inside the cell (Kannaiah et al.) has been incorporated into summaries.

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

2. New in the Biocyc Website

• Improvements have been made to pathway layouts, as well as to display of chemical structures. Pathway diagrams can now depict pathways spanning multiple cellular compartments.

• The organism selector has new options for filtering the set of organisms displayed, such as to see genomes from the NCBI representative genomes set.

Release Notes for BioCyc Version 23.5

Released on December 19, 2019.

Version 23.5 is a major release that includes updates to the BioCyc Web site and downloadable data files, and a new version of the downloadable Pathway Tools software.

Version 23.5 of BioCyc contains 17,043 Pathway/Genome Databases.

1. Improvements to BioCyc Databases

• Bacillus subtilis 168
  • BsubCyc now contains the most recent available genome annotation (February 2018), enhanced by updates from the primary literature: 239 publications from 2018, 204 publications from 2019
  • We added experimental evidence to 21 gene products in BsubCyc

• Pseudomonas putida KT2440
  • We continued literature-based curation of this organism, upgrading a number of protein functions based on new literature information.
  • The database describes the regulation of 452 genes by 25 transcriptional regulators.

New in MetaCyc Version 23.5

MetaCyc now contains 2,766 metabolic pathways. The MetaCyc data were curated from 62,400 publications.

We have added and/or updated 28 pathways in MetaCyc since the last release.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

New in EcoCyc Version 23.5

2. New in the Biocyc Website

• Exporting Pathway Collages to SVG files is now supported to enable higher quality images to be exported.

• BLAST search: We made several improvements to BLAST searches including adding the ability within the BLAST search page to select a different PGDB for searching other than the current PGDB.

• Favorites SmartTable: A "Favorites" SmartTable is now defined for each user. It is accessible through the "Add to SmartTable" button near the top of many pages.

• Pathway Evidence Report Sorted by Pathway Score: A new variant of the pathway evidence report available from command Analysis → Reports → Pathway Evidence sorts the report by pathway score to speed review of low-scoring pathways. Note that older BioCyc databases do not contain pathway scores.

Release Notes for BioCyc Version 23.1

Released on September 19, 2019.

Version 23.1 is a minor release that includes updates to some of the databases at the BioCyc Web site and the corresponding downloadable data files.

Version 23.1 of BioCyc contains 14735 Pathway/Genome Databases.

1. Improvements to BioCyc Databases

• Pseudomonas putida KT2440 -- We upgraded this database to the Tier-2 curation level. Strain KT2440 is the plasmid-free derivative of the toluene-degrading bacterium Pseudomonas putida mt-2, which was originally isolated in 1963 under the name Pseudomonas arvilla mt-2. Unlike strain mt-2, strain KT2440 does not carry the pWW0 TOL plasmid, which is required for toluene degradation. Strain KT2440 is the first Gram-negative soil bacterium to be certified as a safety strain by the Recombinant DNA Advisory Committee, and is considered the best characterized saprophytic Pseudomonad that has retained its ability to survive and function in the environment. It is used worldwide as a workhorse for genetic and physiological studies and for the development of biotechnological applications. Updates to the database include:
  • Propagation of cumulative changes in MetaCyc compounds and reactions, synchronizing the two databases.
  • Rerun of the pathway prediction algorithm, followed by human inspection and pruning of some of the predicted pathways. The pathway count grew by 25, for a total of 330. The number of enzymatic reactions grew from 2,081 to 2,313.
  • Creation of a large number of protein complexes, increasng the total number of complexes from 37 to 180.
  • Propagation of strain KT2440 enzymes that were previously curated in MetaCyc into this PGDB.
  • Curation of several new pathways that were previously not present in MetaCyc.
  • Literature-based curation of 65 proteins [click for listing]

• Saccharomyces cerevisiae S288c -- The YeastCyc database received a major overhaul; for details click here.

New in MetaCyc Version 23.1

MetaCyc now contains 2,749 metabolic pathways. The MetaCyc data were curated from 61,800 publications.

We have added 27 new pathways to MetaCyc since the last release. In addition, we significantly revised 12 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

Release Notes for BioCyc Version 23.0

Released on April 29, 2019.

Version 23.0 is a major release that includes updates to the BioCyc Web site and downloadable data files, and a new version of the downloadable Pathway Tools software.

Version 23.0 of BioCyc contains 14,728 Pathway/Genome Databases.

1. Improvements to BioCyc Databases

• This release includes 170 newly generated PGDBs and 2,390 databases that were re-generated using the latest version of the PathoLogic software and the latest version of the MetaCyc pathway database.

• Salmonella strain LT2 (SENT99287) -- We added a new curated Tier 2 database for Salmonella enterica subsp. enterica serovar Typhimurium strain LT2. New gene functions that were curated with experimental evidence and citations for strain LT2 include:
  • Regulatory protein FimY
  • DNA recombinase Fin
  • Cysteine desulfhydrase CdsH
  • Acid-inducible arylsulfatase AslA
  • NADPH-dependent aldo-keto reductase STM2406
  • A role for GlnA in growth, motility and virulence as a function of glutamine availability
  • Cyclic di-guanylate phosphodiesterase STM0551
  • O-acetyl-serine N-acetyltransferase OatA
  • A key role for PduB in microcompartment assembly
  • Transporter of pantothenate precursors PanS
  • N-acetylneuraminate:Na⁺ symporter STM1128
  • Transcriptional repressor RamR
  • γ-L-glutamyl hydroxamate hydrolase YfeJ

  In addition, enzymes from strain LT2 that were previously curated in MetaCyc were propagated to this PGDB. Enzymes from other strains that were curated in MetaCyc were added as links to MetaCyc in this LT2 PGDB. Enzymes and proteins that were curated in the strain 14028S PGDB were added as hyperlinks in the new PGDB. The latter two categories were briefly annotated with a computational evidence code and citations. Additional enhancements to the new PGDB include: import of external database links, protein features and annotations from UniProt and Pfam; integration of functional annotations derived from BioCyc ortholog computations; and integration of gene functions with experimental evidence listed in Thiele et al 2011) and in Seif et al 2018.

• Salmonella strain 14028S (SENT588858) -- We updated the Tier 2 Salmonella enterica subsp. enterica serovar Typhimurium strain 14028S database with the following new gene functions:
  • Suppressor of flagellin production STM14_2047
  • Swarming motility proteins encoded by yhcO and STM14_1529
  • O-antigen phase variation complex OpvAB
  • Cpx activating connector-like factor A CacA
  • Virulence factors PagK, PagK2 and PagJ
  • Acid and osmotic stress response regulator OmpR.

• Staphylococcus aureus NCTC 8325 (gcf_000013425) -- We added 42 gene names to the Tier 2 Staphylococcus aureus subspecies aureus strain NCTC 8325 PGDB based on an update by AureoWiki in 2018).

New in MetaCyc Version 23.0

MetaCyc now contains 2,722 metabolic pathways. The MetaCyc data were curated from 60,000 publications.

We have added 23 new pathways to MetaCyc since the last release. In addition, we significantly revised 12 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

New in EcoCyc Version 23.0

EcoCyc now contains the equivalent of 3,105 textbook-pages of mini-review summaries for genes, pathways, and regulatory interactions.

• The L-lysine degradation I pathway was significantly updated and extended. Knorr et al. elucidated the functions of several new enzymes in the pathway and showed that the pathway is utilized as an adaptation to stationary phase growth conditions.

• A new pathway, cadaverine biosynthesis, now shows the use of lysine decarboxylation to cadaverine as a mediator of acid resistance (AR4).

• We added 129 regulatory interactions from high-throughput analysis by Aquino et al. for the Nac transcriptional dual regulator.

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

2. New in the Biocyc Website

• Pathway Covering: A new metabolomics analysis operation called Pathway Covering is available. It computes a minimal number of pathways that cover (contain) a supplied set of metabolites. See Analysis → Metabolomics Pathway Coverage.

• Reaction diagrams in reaction pages are now formatted using our improved graphics system.

• Speed improvements have been made to most queries within the Search menu.

Release Notes for BioCyc Version 22.6

Released on December 12, 2018.

Version 22.6 is a minor release that includes updates to the BioCyc Web site and downloadable data files. This release does not include the downloadable Pathway Tools software; its next release is planned for March 2019.

Version 22.6 of BioCyc contains 14,560 Pathway/Genome Databases.

New in MetaCyc Version 22.6

MetaCyc now contains 2,698 metabolic pathways. The MetaCyc data were curated from 58,954 publications. We have added 12 new pathways to MetaCyc since the last release. In addition, we significantly revised 7 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

New in EcoCyc Version 22.6

We have added 2 new pathways to EcoCyc since the last release. The EcoCyc data were curated from 36,151 publications.

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

Release Notes for BioCyc Version 22.5

Released on Sep 25, 2018.

Version 22.5 is a major release that includes updates to the BioCyc Web site and downloadable data files, and a new version of the downloadable Pathway Tools software.

Version 22.5 of BioCyc contains 14,560 Pathway/Genome Databases.

1. Improvements to BioCyc Databases

• This version includes 1500 newly generated databases and 800 databases that were re-generated using the latest version of the PathoLogic software and the latest version of the MetaCyc pathway database. All of the new and re-generated databases are microbial genomes from the Human Microbiome Project.

• We updated the Mycobacterium tuberculosis H37Rv PGDB with curation of 40 new experimentally determined gene functions (enzymatic and regulatory) from the scientific literature. We updated the external database links to Mycobrowser and the Protein Data Bank, and updated the Gene Ontology annotations. We also imported protein functions from UniProt for 136 uncurated proteins that were not annotated with a specific function. In addition, we upgraded the PGDB with data (e.g., corrected chemical structures and reactions) from the newly released MetaCyc version 22.5. Click here for a list of all Mycobacterium tuberculosis H37Rv genes with curated (experimentally studied) functions.

• We updated the Staphylococcus aureus NCTC 8325 PGDB. Click here for a list of all Staphylococcus aureus NCTC 8325 genes with curated (experimentally studied) functions. Recent curation included the genes:
  • fakA
  • fakB2
  • fakB1
  • gdpP
  • pde2

  and pathway staphylopine biosynthesis and associated enzymes encoded by genes:

  • cntK
  • cntL
  • cntM

  and pathway staphyloferrin B biosynthesis and associated enzymes encoded by genes:

  • sbnI
  • sbnA
  • sbnB
  • sbnE
  • sbnH
  • sbnF
  • sbnC

New in MetaCyc Version 22.5

MetaCyc now contains 2,666 metabolic pathways. The MetaCyc data were curated from 58,000 publications.

We have added 26 new pathways to MetaCyc since the last release. In addition, we significantly revised 19 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information.

For more details see https://BioCyc.org/metacyc/release-notes.shtml.

New in EcoCyc Version 22.5

EcoCyc now contains the equivalent of 3,105 textbook-pages of mini-review summaries for genes, pathways, and regulatory interactions.

New GenBank File for Escherichia coli K-12 MG1655 Released!

The most recent prior update to U00096.3 was released on August 1, 2014. The version suffix is changed only when the nucleotide sequence has changed -- thus the version number remains the same for this new release because no changes have been made to the nucleotide sequence. This new update does contain a large number of other changes based on publications in the past four years. The most significant updates include:

• Newly discovered gene functions, including gene and product name changes
• Newly discovered genes and gene products
• Updated gene product names to conform to UniProt and NCBI guidelines

Highlights of EcoCyc Database Improvements

• We have added gene and protein objects for 32 new small proteins recently identified by VanOrsdel et al.

• We have updated the drug efflux proteins represented in EcoCyc. Text summaries for 11 complexes and 40 proteins have been revised and/or updated; 19 new transport reactions, 30 compounds (antibiotics, dyes and other toxins) and just under 200 literature references were added to the database as part of this project. Click here for a SmartTable of all E. coli transporters of known function. A new function was also added to the small multidrug resistance (SMR) family transporter, Gdx (formerly SugE) - characterized by Kermani et al. as a proton-coupled guanidinium exporter.

• Fitzgerald et al. showed that binding sites for the alternative sigma factor FliA represent active promoters that transcribe highly unstable RNAs.

• Insertion sequences and prophages are now represented as database objects within EcoCyc, enabling their inclusion in the generated Genbank file.

• A number of crystal and solution structures for the transcription machinery and transcriptional regulators have been published, including:
  • RNA polymerase by Molodtsov et al. and Narayanan et al.
  • RcsB by Filippova et al.
  • CpxA/ CpxR by Mechaly et al.
  • PhoB by Kou et al.

• We have added one new pathway to EcoCyc: prenylated FMNH₂ biosynthesis

For more details see https://BioCyc.org/ecocyc/release-notes.shtml.

2. New in the Biocyc Website

• New Search Commands: The following new search commands have been added:
  • Search for cryptic prophages via Search → Search DNA or RNA sites → Search by site type → Cryptic Prophages
  • Search for pseudogenes via Search → Search genes, proteins, or RNAs → Search/filter by type/subunits → Pseudogenes only

• Performance Enhancements: We have engineered a number of performance enhancements, particularly to decrease the time to generate gene pages.

• Pseudogenes: Our internal representations for pseudogenes have changed to provide more consistent and comprehensive treatment of pseudogenes.

3. BioCyc Operations -- Monitoring the Error Log

Our programming team receives an email each night containing a summary of the error log, which we inspect to determine what errors are occurring, and with what frequency. We pursue the most frequent errors first. In most cases we are able to fix the problem within a day, and issue a patch that is incorporated by our running web servers, and is loaded by remote users of Pathway Tools the next time they start the software.

Release Notes for BioCyc Version 22.0

Released on April 24, 2018.

• Version 22.0 is a major release that includes updates to the BioCyc Web site, downloadable data files, and downloadable software/database bundles.

• Version 22.0 of BioCyc contains 13076 Pathway/Genome Databases.

• We added a curated database for Staphylococcus aureus NCTC 8325 to BioCyc.

• We added five additional pan-genome databases to BioCyc for Escherichia coli, Helicobacter pylori, Salmonella enterica, Shigella flexneri, and Vibrio cholerae.

• MetaCyc now contains 2,609 metabolic pathways; the MetaCyc data were curated from 55,600 publications. We added 37 new pathways to MetaCyc since the last release.

• EcoCyc now contains 347 metabolic pathways; the EcoCyc data were curated from 34,421 publications. We added 2 new pathways to EcoCyc since the last release.

New in the Biocyc Website

• Pathway regulation: Pathway diagrams can now include detailed regulatory information for each step that are taken from the regulatory data present within a given PGDB. From any pathway page, such as L-homoserine biosynthesis, click on the "Show Regulation Details" button above the pathway diagram to see transcriptional, translational and substrate-level regulators included in the diagram. This button will only be present if there is regulation data available for the pathway, and if the pathway is displayed at a detail level that shows enzyme names. Mouse over any regulator icon for more information. Mouse over regulation arrows to identify which ligands influence specific isozymes.

• Cellular Overview reborn: The BioCyc cellular overview (metabolic map) diagram has been re-engineered to use modern web graphics. See Metabolism → Cellular Overview. The graphics now look sharper, and you can zoom the diagram quickly using your mouse wheel (the +/- bar at the upper left provides finer zoom control). When using the diagram in its Omics Viewer mode to display transcriptomics or metabolomics data, the sliders at the top of the diagram enable you to optimize the diagram by controlling the opacity of the diagram, the thickness of all edges in the diagram, and the thickness of the highlighted edges in the diagram. Additional sliders in the omics dialog enable thresholding of what omics data are visible.

  New webinars are available to explain the usage of the basic Cellular Overview and how to analyze omics data with the Cellular Overview.

• Metabolic model fluxes on Omics Dashboard: A new method is available for viewing the fluxes computed by running BioCyc metabolic models. Previously, after running a metabolic model (command Metabolism → Run Metabolic Model), the user could display the computed fluxes on the Cellular Overview diagram. Now, a new button "Show Fluxes on Dashboard" enables the user to also display the fluxes on the Omics Dashboard tool. This tool enables the user to both view reaction fluxes aggregated at the pathway or subsystem level (e.g., to view the integrated behavior of all amino acid biosynthetic reactions), and to drill down to see fluxes for individual pathways and reactions.

New in EcoCyc Version 22.0

Highlights of EcoCyc Database Improvements

• A new electron transport reaction has been added and assigned to the periplasmic protein Ccp (formerly YhjA), characterized by Kademian et al. as a cytochrome c peroxidase which uses membrane quinones for the reduction of hydrogen peroxide.

  Two new pathways have been added to EcoCyc to reflect Ccp's role in anaerobic respiration:

  • NADH to hydrogen peroxide electron transfer
  • glycerol-3-phosphate to hydrogen peroxide electron transport

• The curation of exodeoxyribonuclease V (RecBCD), rhomboid protease (GlpG) and K⁺-transporting P-type ATPase (KdpFABC) has been revised and updated for this release. Reactions catalysed by ExoV and GlpG are now more accurately represented, and literature coverage has been extended significantly for all three.

• 5-Oxo-L-proline is a cyclic metabolite that is deleterious to the cell. An ATP-dependent 5-oxoprolinase was recently discovered by Niehaus et al..

For more details see http://BioCyc.org/ecocyc/release-notes.shtml.

New in MetaCyc Version 22.0

We have added 37 new pathways to MetaCyc since the last release. In addition, we significantly revised 8 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 45 new and updated pathways.

For more details see http://BioCyc.org/metacyc/release-notes.shtml.

Improvements to other BioCyc Databases in Version 22.0

• We generated 113 new Staphylococcus aureus PGDBs in BioCyc, bringing the total number of S. aureus strains in BioCyc to 242

• We regenerated the BioCyc PGDB for S. aureus NCTC 8325, and performed extensive literature-based curation of this strain. The database now cites more than 500 publications.
  • We integrated assigned gene names and protein functions from UniProt, AureoWiki, MetaCyc, the literature, and from the non-RefSeq GenBank file. We thank UniProt and AureoWiki for use of their data.
  • We curated many S. aureus genes, adding mini-review summaries, reactions, evidence codes, and literature citations.
  • We reviewed and updated transporters and their assigned transport reactions.
  • We updated links from the strain NCTC 8325 PGDB to other databases such as UniProt and AureoWiki.
  • We imported Gene Ontology annotations from UniProt.
• We generated new pan-genome databases in BioCyc, which now contains pan-genome databases for the organisms below (new organisms are in bold face). You can find them by entering "pan-genome" in the "change organism database" dialog.
  • Clostridioides difficile
  • Escherichia coli
  • Helicobacter pylori
  • Listeria monocytogenes
  • Mycobacterium tuberculosis
  • Pseudomonas aeruginosa
  • Salmonella enterica
  • Shigella flexneri
  • Vibrio cholerae

• The Bacillus subtilis database BsubCyc received pathway and enzyme curation. Click here for details.

Release Notes for BioCyc Version 21.5

Released on November 28, 2017.

• Version 21.5 is a major release that includes updates to the BioCyc Web site, downloadable data files, and downloadable software/database bundles.
• Version 21.5 of BioCyc contains 10,980 Pathway/Genome Databases.
• MetaCyc now contains 2,609 metabolic pathways; the MetaCyc data were curated from 55,600 publications. We added 37 new pathways to MetaCyc since the last release.
• EcoCyc now contains 347 metabolic pathways; the EcoCyc data were curated from 34,421 publications. We added 2 new pathways to EcoCyc since the last release.

New in the Biocyc Website

• Omics Dashboard: The Dashboard is an interactive tool for exploration and analysis of gene-expression and metabolomics datasets (see Dashboard publication in Nucleic Acids Research). For more information see the Dashboard Help document and Webinar #7 describing the Omics Dashboard. New Dashboard features added in this version include the following.
  • Extended the list of top-level panels to include several panels of non-metabolic functions including a panel for sigma factor regulons
  • "Show Genes Not Present in any Subsystem" button generates a list of genes not mapped to any panel
  • Added ability to search for a given gene by name and have the Dashboard open the panel hierarchy to show that gene (see Search link at top of page)
  • The experiment legend is shown at top of every pane
  • New options for creating publication-quality diagrams:
    • "Hide Controls" option removes all option buttons. The user can also now hide the control panel accordion on the right of the page.
    • User can now specify y-axis legend
    • "Hide Panel" command is now present in every panel's Options menu to unshow the panel
  • Regulator panel: added disjunction option, added list of regulators to tooltip for gene
  • Handle multiple replicons when sorting by map position
  • Put tooltips on the genes in the operon diagrams, and made the diagrams clickable
  • Add ability to generate empty dashboard for explanatory purposes
  • Added "Panel Description" command to panel Options menu to let users find out which GO terms are being used to define a given segment within the dashboard
  • Pwy diagrams: color scheme cutoff now computed only from data in diagram.
  • When generating pathway collage from dashboard image, keep user-specified color scale

• Omics Pop-ups Use Google Charts: Previously the Omics Pop-ups used Adobe Flash, but as Flash is no longer supported by some browsers, we have re-implemented the Omics Pop-ups using Google Charts.

• Improved Graphics and Fonts: We have upgraded many additional Web visualizations produced by Pathway Tools in its web server mode to use modern graphics and fonts, including the genome browser; genome overview; transport reactions; operon diagrams; transcription-unit diagrams; functionally-linked gene cluster diagrams; gene-neighbor diagrams; mapped-genes diagram; protein features; and sequence diagrams for promoters, binding-sites, and attenuators.

New in EcoCyc Version 21.5

Highlights of EcoCyc Database Improvements

• A new electron transport reaction has been added and assigned to the periplasmic protein Ccp (formerly YhjA), characterized by Kademian et al. as a cytochrome c peroxidase which uses membrane quinones for the reduction of hydrogen peroxide.

  Two new pathways have been added to EcoCyc to reflect Ccp's role in anaerobic respiration:

  • NADH to hydrogen peroxide electron transfer
  • glycerol-3-phosphate to hydrogen peroxide electron transport

• The curation of exodeoxyribonuclease V (RecBCD), rhomboid protease (GlpG) and K⁺-transporting P-type ATPase (KdpFABC) has been revised and updated for this release. Reactions catalysed by ExoV and GlpG are now more accurately represented, and literature coverage has been extended significantly for all three.

• 5-Oxo-L-proline is a cyclic metabolite that is deleterious to the cell. An ATP-dependent 5-oxoprolinase was recently discovered by Niehaus et al..

For more details see http://BioCyc.org/ecocyc/release-notes.shtml.

New in MetaCyc Version 21.5

We have added 37 new pathways to MetaCyc since the last release. In addition, we significantly revised 8 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 45 new and updated pathways.

For more details see http://BioCyc.org/metacyc/release-notes.shtml.

Improvements to other BioCyc Databases in Version 21.5

• Approximately 2,000 BioCyc databases were re-generated from the latest RefSeq entries, using the latest version of the PathoLogic software against the latest version of the MetaCyc pathway database.

• The HumanCyc database received extensive updates, including addition of 12 new pathways and updates to include the UniProt human proteome set. Click here for details.

• The Bacillus subtilis database BsubCyc received pathway and enzyme curation. Click here for details.

Use wget to Download BioCyc Files

Release Notes for BioCyc Version 21.1

Released on August 15, 2017.

Version 21.1 is a minor release that includes updates to the BioCyc Web site and downloadable data files. This release does not include the downloadable Pathway Tools software; its next release is planned for November.

Version 21.1 of BioCyc contains 11,000 Pathway/Genome Databases (an increase of more than 1,500 organisms).

Significant Curation Updates in Version 21.1

• YeastCyc: We have added 3 new pathways to YeastCyc and updated the curation of multiple enzymes. We have also updated the database to contain recent updates to MetaCyc metabolites and reactions.
  New Pathways:
  • heme a biosynthesis
  • homofuraneol biosynthesis
  • tRNA-uridine 2-thiolation (yeast mitochondria)

New in EcoCyc Version 21.1

• Three new pathways have been added to EcoCyc:
  • L-cysteine biosynthesis VII
  • lipoprotein posttranslational modification
  • tRNA-uridine 2-thiolation (bacteria)

• New information has been added for several membrane proteins including YhhQ - implicated in the uptake of queuosine precursors for salvage; MgtS (formerly YneM) - required for accumulation of the magnesium transporter MgtA under magnesium limiting conditions, and YbaT - which, along with glutaminase I, functions to overcome disrupted glutamate synthesis under copper stress conditions.

• The curation of DNA repair proteins AlkB and Endonuclease VIII has been revised and updated for this release; reactions catalyzed by these enzymes are now accurately represented and literature coverage has been extended significantly.

For more details including database statistics see http://BioCyc.org/ecocyc/release-notes.shtml

New in MetaCyc Version 21.1

We have added 45 new pathways to MetaCyc since the last release. In addition, we significantly revised 13 pathways by modifying pathway diagrams, adding commentary, and updating enzyme and gene information, for a total of 58 new and updated pathways. We also added commentary to 11 existing superpathways.

Release Notes for BioCyc Version 21.0

Released on April 27, 2017.

• Version 21.0 is a major release that includes updates to the BioCycWeb site and downloadable data files, and a new version of the downloadable Pathway Tools software.
• Version 21.0 of BioCyc contains 9,389 Pathway/Genome Databases.
• In EcoCyc we added one new pathway, updated curation of proteins belonging to the ABC family of transporters, revised text summaries for 59 complexes and 209 proteins, and added over 300 references.
• MetaCyc now contains 2,526 metabolic pathways. The MetaCyc data were curated from 52,000 publications.

New in the Biocyc Website

• Omics Dashboard: The Dashboard is an interactive tool for exploration and analysis of gene-expression and metabolomics datasets. For more information see Webinar #7 describing the Omics Dashboard
• Improved Graphics and Fonts: We have upgraded some of the visualizations produced by Pathway Tools in its web server mode to use modern graphics and fonts, such as the Regulation Summary Diagram on gene pages.
• Multi-Organism Metabolic Route Search: The metabolic route search capability has been extended to enable searches across organism communities

Release Notes for BioCyc Version 20.5

Released on December 17, 2016.

• Version 20.5 is a major release that includes updates to the BioCyc Web site, downloadable data files, and downloadable software/database bundles.
• Version 20.5 of BioCyc contains 9,387 Pathway/Genome Databases.
• MetaCyc now contains 2,507 metabolic pathways; the MetaCyc data were curated from 51,500 publications. We added 11 new pathways to MetaCyc since the last release.

New in the Biocyc Website

• Receive Notification of Database Updates -- This new facility allows scientists to sign up to be notified of curation of new information in their research interest area(s). Sign up via the Update Notifications Page (available through Analysis → Update Notifications) to be notified when new curation (which indicates new published experimental findings) occurs for specific genes or metabolic pathways. You can also sign up for notifications in interest areas specified by Gene Ontology terms, such as cell motility or cell division -- you will then be notified whenever new curation occurs in genes involved in those biological processes. Notifications will be sent by email in conjunction with BioCyc releases.

• Expanded Organism Searches: The "search by organism properties" option within the organism selector menu in the upper-right corner of most BioCyc pages includes additional searches to enable users to find BioCyc databases based on the amount of data of different types present in the database, including:
  • Number of Gene Ontology terms
  • Number Phenotype Microarray datasets
  • Number of gene essentiality datasets
  • Number of genes with essentiality data
  • Number of transcriptional regulatory interactions (i.e., size of regulatory network present)

• Revised Protein Feature Coloring: We have revised the coloring scheme within the protein-feature display to assign a fixed set of colors to different feature types. For example, all enzyme active site features will be colored purple.

Significant Curation Updates in Version 20.5

• Updates to BsubCyc Bacillus subtilis 168 Database. Updates included addition of two new transcription factors, five transcription units, and seven transcription start sites with experimental evidence. 22 additional proteins are now associated with one or more GO terms with experimental evidence, and 85 new citations were added to papers published in 2016, for a total of 163.

  Example updates include include the transcription factors ThrR, GabR, the regulator of DNA replication initiation YabA, the YaaT-YlbF-YmcA regulatory complex, and the bacillithiol biosynthesis enzyme L-malate glycosyltransferase.

• We created and refined new Tier 2 PGDBs for the following human microbiome bacteria. We reviewed and curated enzyme-reaction assignments and inferred pathways, reviewed computationally inferred transport reactions, and executed the Pathway Tools pathway hole filler.
  • Desulfovibrio piger ATCC 29098
  • Faecalibacterium prausnitzii A2-165
  • Prevotellacopri DSM 18205
  • [Clostridium] symbiosum WAL-14163

New in EcoCyc

New in MetaCyc

New Pan-Genome Databases in BioCyc

New Gene Essentiality Datasets in BioCyc

The following organism databases include the newly added gene essentiality data. To access a given gene essentiality dataset, click on the Growth-Media page for a given organism below, and then click on a growth medium to see a list of all genes that are essential in that medium. In additional, gene pages list essentiality data for that gene when available.

Release Notes for BioCyc Version 20.1

Released on Sep 29, 2016.

• Version 20.1 is a minor release that includes updates to the BioCyc Web site and downloadable data files.
• Version 20.1 of BioCyc contains 7,600 Pathway/Genome Databases.
• In EcoCyc we added two new pathways and revised several periplasmic proteins.
• MetaCyc now contains 2,492 metabolic pathways; the MetaCyc data were curated from 50,700 publications. We added 38 new pathways to MetaCyc since the last release.

New Gene Essentiality Datasets in BioCyc

To access a given gene essentiality dataset, click on the Growth-Media page for a given organism below, and then click on a growth medium to see a list of all genes that are essential in that medium. In additional, gene pages list essentiality data for that gene when available.

• Acinetobacter sp. ADP1
• Homo sapiens
• Francisella tularensis novicida U112
• Haemophilus influenzae Rd KW20
• Helicobacter pylori 26695
• Mycobacterium tuberculosis H37Rv
• Mycoplasma genitalium G37
• Mycoplasma pulmonis UAB CTIP
• Pseudomonas aeruginosa UCBPP-PA14
• Saccharomyces cerevisiae S288c
• Salmonella enterica enterica serovar Typhi str. CT18
• Salmonella enterica enterica serovar Typhimurium str. LT2
• Staphylococcus aureus aureus NCTC 8325
• Streptococcus pneumoniae D39
• Streptococcus pneumoniae R6
• Streptococcus pneumoniae TIGR4

Significant Curation Updates in Version 20.1

• We created and refined a new Tier 2 PGDB for Lactobacillus rhamnosus GG, a human microbiome organism and a well documented probiotic strain. Refinements include review of inferred pathways, review of inferred transport reactions, and supervised execution of the Pathway Tools pathway hole filler.

• New curation added to the Tier 2 PGDB for Corynebacterium glutamicum ATCC 13032 includes a superpathway for aromatic compound degradation and a biosynthetic pathway for the cyclic C50 carotenoid decaprenoxanthin. A number of enzymes and transporters associated with these pathways were also curated. Other newly curated enzymes and transporters include Ldh, LldD, Dld, CglK, Kup and BetP.

New in EcoCyc

New in MetaCyc

Release Notes for BioCyc Version 20.0

Released on May 9th, 2016.

• Version 20.0 of BioCyc contains 7,600 Pathway/Genome Databases.

• EcoCyc now contains the equivalent of 2,700 textbook-pages of mini-review summaries. The EcoCyc data were curated from 31,000 publications.

• MetaCyc now contains 2,400 metabolic pathways; the MetaCyc data were curated from 49,000 publications. We added 44 new pathways to MetaCyc since the last release. In addition, we significantly revised 21 pathways by adding commentary and updated enzyme and gene information.

New in the Biocyc Website

• Run metabolic models using web interface: You can now run metabolic models via the BioCyc website with a few mouse clicks, as follows:
  • Find BioCyc organisms with metabolic models by clicking "change organism database", then select the tab "Having Metabolic Models". Click the organism for which you want to run a model and click OK.
  • Then run command Metabolism ? Run Metabolic Model and follow the instructions.
  • Example: Click here to run the EcoCyc metabolic model.
  • Models are available on BioCyc.org for two other gut-microbiome bacteria.

• Metabolic and genome posters for all BioCyc organisms are available -- see the commands Metabolism ? Generate Metabolic Map Poster and Genome ? Generate Genome Poster.

• Re-designed metabolite pages: BioCyc metabolite pages have been re-designed to structure metabolite information across multiple tabs to make information easier to find and assimilate.

• Search for DNA sites: The new command Search ? Search DNA or mRNA Sites enables searches for sites such as promoters and attenuators, potentially filtering by replicon, nucleotide coordinates, and ligands.

• Pathway Perturbation Scores: The command to generate a table of pathways overlaid with omics data now ranks pathways by Pathway Perturbation Score, a new score that attempts to measure the degree to which the expression level of a pathway is perturbed over the course of an omics experiment. From the website Metabolism ? Cellular Overview page, select "Upload Data from File" and ask to show the data as a table of pathway diagrams.

• New Cellular Overview highlighting commands: Several new commands are available to help you find information within the Cellular Overview (metabolic map) diagram. Under the right-sidebar menu, see these new commands:
  • Highlight reaction by enzyme cellular location
  • Highlight reaction by modulation (finds reactions according to substrate-level regulation of enzyme activity)
  • Highlight enzyme by curation

• Gene/reaction schematic improvements: The gene/reaction schematic diagram has been improved to reduce the size of large tangled sets of gene-reaction relationships by truncating such diagrams. A button is now provided to allow the user to toggle between full and truncated versions of the diagram.

• Improved command to Search for Reactions by Substrates: This command, which enables users to search for reactions by specifying one or more substrates, now enables users to specify which side of the reaction different substrates are on, relative to each other (see Search ? Search Reactions).

• New Pathway Collages page: The new page Metabolism ? Pathway Collages enables users to generate a pathway collage (a personalized multi-pathway diagram) by selecting from a list of all pathways in the current database.

Significant Curation Updates

• Corynebacterium glutamicum: Included in this BioCyc release is a new curated (Tier 2) PGDB for the industrially important organism Corynebacterium glutamicum ATCC 13032. This organism is used in the engineered production of amino acids and other compounds. The PGDB is based on GenBank record BA000036.3, but also incorporates some gene function annotations from GenBank record BX927147.1. It contains over 200 inferred pathways and 92 inferred transport reactions. We performed a thorough review of the PathoLogic pathway prediction, manually assigned a number of enzymes to their catalyzed reactions, and performed literature searches and curation for a number of enzymes. We will continue curation on an ongoing basis.
• Mycobacterium tuberculosis: A curated database for the H37Rv strain was launched in February 2016. This database, BioCyc MtbH37Rv, was generated from Genbank record AL123456.3, which was revised in December 2012 to contain the latest annotation from Tuberculist. We performed literature searches and curation for 155 proteins, resulting in the addition of 55 textbook-page equivalents of mini-reviews to these proteins. The database cites 1,700 literature references from which the enhanced curation was derived. Literature curation was added for 34 metabolic pathways, including authoring of 32 textbook-page equivalents of mini-reviews to these pathways. Drug screening data for more than 700 compounds, assembled by Ekins et al (J Cheminform 5(1):13 2013), has been included in BioCyc MtbH37Rv; those compounds are listed under the compound class "anti-tuberculosis compound" (see the Ontology tab).

Release Notes for BioCyc Version 19.5

Released on Nov 12, 2015.

• Version 19.5 of BioCyc contains 7,667 Pathway/Genome Databases.

• This version of BioCyc contains a new pan-genome Pathway/Genome Database for Mycobacterium tuberculosis that integrates genes from 25 M. tuberculosis strains into one database. That PGDB also contains the pathways predicted from this multi-strain gene set. For more information about pan-genome PGDBs, click here. To select this PGDB, search for "pan-genome" in the organism selector.

• This new release includes 2 new pathways in EcoCyc.

• MetaCyc now contains 2,411 metabolic pathways and 13,074 reactions; its contents have been curated from over 47,800 publications.

BioCyc Web Site Improvements

• Redesigned gene pages: We have redesigned the Web gene pages for a more modern look and to make information easier to find. Gene pages now contain a series of tabs; clicking on a given tab shows a specific type of information, such as the reactions catalyzed by a gene product, the GO terms assigned to the gene, or the features defined for the gene product. Note that the set of tabs present varies depending on the type of the gene product and the information available. The "Show All" tab combines all information in one page for easier searching.

• New pathway collage feature: A pathway collage is a diagram depicting a set of connected metabolic pathways, possibly with omics data superimposed (example here). You can now interactively create a pathway collage in Pathway Tools desktop and Web modes. To create a pathway collage in Web mode:
  • (Optional) Load a gene expression or metabolomics data file if you want to include such data within your collage, by bringing up the cellular overview (Metabolism → Cellular Overview) and then running Right-Sidebar Menu → Overlay Experimental Data (Omics Viewer) → Upload Data from File.

  • Specify the pathways to include in the collage in one of two ways:
    • Go to any pathway page and then invoke Right-Sidebar Menu → Generate Pathway Collage.
    • Create a SmartTable containing the pathways to include in the collage and then invoke Right-Sidebar Menu → Export → Export Pathways to Pathway Collage.

  • The collage will be created in your web browser, where you will be able to reposition the pathways interactively, add additional pathways to the collage, add connections between metabolites, change various display styles, and view omics data, to create your desired diagram. Export the diagram to a file for inclusion in a publication. For more details see the Website User's Guide.
• New Cellular Overview queries: New Web Cellular Overivew query operations include:
  • Highlight Genes → By replicon and By Regulon
  • Highlight Reactions → By Evidence
  • Highlight Pathways → By Curation and By Evidence.

• Many performance improvements and bug fixes have been made to SmartTables.

• Performance improvements have been made to Search → Cross Organism Search.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• Dynamic FBA: MetaFlux can now perform dynamic FBA in addition to the previous steady-state FBA. In dynamic FBA, a steady-state metabolic model can be executed across multiple time steps File enzymes-table.shtml not found for system biocyc! Aborting!Dynamic FBA can be applied to single organisms or to organism communities to predict changes in organism abundance over time. New nutrients and organisms can be introduced at specific grid points and specific times during a simulation.

• Model a spatial grid: Models can now be executed across a user-defined rectangular grid in addition to the previous single spatial compartment. Diffusion of cells and small molecules is simulated across the grid.

• New graphical outputs: Model results can be viewed using several new tools such as viewing the time course of organism biomass changes and metabolite concentration changes, both overall, and across the grid. Results can be viewed as static X-Y plots and as MetaFlux-generated videos.

EcoCyc release notes: http://ecocyc.org/release-notes.shtml

MetaCyc release notes: http://metacyc.org/release-notes.shtml

Release Notes for BioCyc Version 19.1

Released on June 24, 2015.

Version 19.1 of BioCyc contains 5,711 Pathway/Genome Databases.

This new release includes eight new pathways in EcoCyc.

MetaCyc now contains 2,363 metabolic pathways and 12,700 reactions; its contents have been curated from over 46,000 publications.

Release Notes for BioCyc Version 19.0

Released on March 20, 2015.

Version 19.0 of BioCyc contains 5,500 Pathway/Genome Databases.

BioCyc Web Site Improvements

• Genome browser: The Pathway Tools genome browser now depicts transcription factor binding sites and attenuators, and will display the nucleotide sequence at high magnification levels.

• Sequence variant data analysis: Web SmartTables support a new analysis operation for sequence variant data. The user can define a SmartTable of replicon regions and associated sequence variants via a file import operation. Then, the SmartTables transformation "Sequence -- nearest gene to DNA region" adds additional columns to the SmartTable showing the nearest gene to each region, and the amino-acid change caused by each sequence substitution.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• Sequence Editor: A new interactive sequence editing tool is available for making manual updates to a replicon sequence. See Chromosome → Edit Nucleotide Sequence.

• MetaFlux Metabolic Modeling Tool
  • Model development mode now includes reporting of blocked reactions, and improved taxonomic reaction information when gap filling.

  • Several improvements have been made to display of reaction fluxes on the metabolic map diagram.

Transcriptional Regulation Data Imported from RegTransBase and TractorDB

• RegTransBase is a database of prokaryotic transcriptional regulation manually curated from the literature. Data describing approximately 2100 transcription-units, 1100 promoters and 1300 transcription factor binding sites across 149 organisms, including literature citations, were imported from RegTransBase into BioCyc. About a third of the imported data pertains to just three organisms: Corynebacterium glutamicum ATCC 13032, Pseudomonas aeruginosa PAO1, and Streptomyces coelicolor A3(2). This information is visible on the gene page for both transcriptional regulators and genes regulated by transcriptional regulators (e.g. RhlR), with more details on the transcription-unit page (e.g. rhlR transcription unit).
• TractorDB is a database of computationally predicted transcription factor regulatory sites in a handful of gamma-proteobacteria. Approximately 9000 predicted regulatory interactions across 25 organisms were imported from TractorDB into BioCyc.

EcoCyc release notes: http://ecocyc.org/release-notes.shtml

MetaCyc release notes: http://metacyc.org/release-notes.shtml

Release Notes for BioCyc Version 18.5

Released on Nov 07, 2014.

Version 18.5 of BioCyc contains 5,500 Pathway/Genome Databases.

BioCyc Web Site Improvements

• Metabolomics and gene expression operations: Muliple new metabolomics and gene-expression operations are available in web and desktop modes.

• More flexible omics-data file formats: We have extended the BioCyc omics-data loading software to recognize a wider variety of gene and metabolite names and identifiers in the first column of the file.

• Quick Search locus IDs: The Web quick-search box now accepts an additional search option: enter a gene locus ID from any BioCyc genome, regardless of the currently selected organism. Example: entering MSM_0046 will find an NADH oxidase in Methanobrevibacter smithii.

• Omics popups on pathway pages: The pathway customization options have been extended to support upload of omics datasets with multiple timepoints, displayed using omics popups. Visit any pathway page and choose the "Customize or Overlay Omics Data on Pathway Diagram" operation.

• iPhone/iPad app generalized to access any PGDB in any pathway tools web server: Initially, our EcoCyc app provided access to the EcoCyc database only, on the iPhone only. Then we expanded it to work on the iPad. In this release we have renamed the app "BioCyc," and it now enables users to access any database in BioCyc, and any database in any other Pathway-Tools-based website that is running version 18.5 or later of Pathway Tools.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• PythonCyc: A new Python API is available for Pathway Tools. It supports programmatic querying and updating of PGDBs via Python. For more information, see the PythonCyc Overview page.

• MetaFlux Metabolic Modeling Tool
  • Metabolic models of organism communities: MetaFlux now supports construction of quantitative metabolic models for communities of organisms, such as bacteria within the human microbiome.

  • Inference of biomass metabolite list: MetaFlux can now generate a suggested biomass metabolite list for many organisms by using biomass compositions recorded for nine different taxonomic groups.

EcoCyc release notes: http://ecocyc.org/release-notes.shtml

MetaCyc release notes: http://metacyc.org/release-notes.shtml

Release Notes for BioCyc Version 18.1

Released on June 23, 2014.

Version 18.1 of BioCyc contains 3,563 Pathway/Genome Databases.

Release Notes for BioCyc Version 18.0

Released on March 24, 2014.

Version 18.0 of BioCyc contains 3,531 Pathway/Genome Databases.

BioCyc Web Site Improvements

• Cross-Organism Search: This new tool enables name-based searches across specified sets of organisms in BioCyc. For example, you can search a specified taxonomic group in BioCyc (e.g., all cyanobacteria) for metabolites (or proteins, or pathways) having a certain substring in their name (e.g., achromobactin).

• Groups / SmartTables Enhancements:
  • Groups have been renamed to SmartTables.
  • Given a SmartTable containing genes or proteins, you can invoke a multiple sequence alignment for those genes or proteins
  • The SmartTable right-sidebar menus have been re-organized.
  • The icons in column headers have been re-organized with some options moved to the right-sidebar menus. A new collapse-column option is available.
  • Several performance improvements have been made for large SmartTables
  • Added support for peptide regions as a SmartTable object type.

• Sequence pattern searches: You can now search a genome for exact or degenerate short patterns of nucleotides or amino acids.

• Sequence alignments: You can now obtain multiple sequence alignments for genes and proteins, both within a genome and across genomes.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• Quicksearch: The new desktop quicksearch toward the bottom left of the screen is analogous to the web quicksearch: it performs a substring search with the user's input word(s) against the names of most entities in the current PGDB, including genes, compounds, and pathways.

• SBML Import Tool: A new tool allows you to import an SBML file into a new or existing PGDB. The tool creates all metabolites and reactions defined in the SBML file in the PGDB, and attempts to map those metabolites and reactions to metabolites and reactions in MetaCyc.

EcoCyc release notes: http://ecocyc.org/release-notes.shtml

MetaCyc release notes: http://metacyc.org/release-notes.shtml

Release Notes for BioCyc Version 17.5

Released on October 11, 2013.

Version 17.5 of BioCyc contains 2,988 Pathway/Genome Databases.

BioCyc Web Site Improvements

• New Right-Sidebar Menu: The previous object-specific menus have been replaced by a right-sidebar menu of operations that changes depending on what type of page the user is visiting. For example, the menu of operations differs for pathway pages versus metabolite pages. Some operations previously accessible by buttons (e.g., retrieving a protein sequence) are now accessible through this new right menu in gene pages. If you do not see the menu, please reload the page in your web browser while holding down the "Shift" key.

• Web Cellular Overview and Omics Viewer: This tool has undergone a major overhaul including
  • It runs much faster and many bug fixes have been made
  • Gene expression data to be displayed on the Cellular Overview can now be retrieved from PortEco, from GEO, and from Web Groups
  • Pop-up improvements
  • Many new search commands are available
  • Labels for pathway groups are now included in the diagram

• Groups Enhancements: A number of enhancements have been made to both Web Groups including:
  • Groups can now be published. Once published a group is publically readable, and the group cannot be deleted, even by its owner. The idea is to encourage scientists to refer to published groups in their scientific publications.
  • Users can now create temporary groups without creating a BioCyc account to facilitate experimentation with Groups.
  • Database identifiers in database links can be added as groups columns, e.g., KEGG IDs for BioCyc compounds.
  • A group of objects can be created via text entry.
  • New row selection operations are available.
  • The star in the heading of the first column allows the user to toggle between viewing object names and object identifiers.

• Full Pathway Tools release notes: http://bioinformatics.ai.sri.com/ptools/release-notes.html

MetaCyc release notes: http://metacyc.org/release-notes.shtml

Release Notes for BioCyc Version 17.0

Released on March 29, 2013.

Version 17.0 of BioCyc contains 2,920 Pathway/Genome Databases.

BioCyc Web Site Improvements

• Groups Enhancements: A number of enhancements have been made to both Web Groups and Desktop Groups including re-organization of Web Groups menus and addition of new transformations.

• Phenotype Microarrays and Other Growth Data: The displays of growth media, growth observations, and phenotype microarray data has been substantially revised.

• Metabolic Route Search: The new RouteSearch tool, accessible from command Tools -> Metabolic Route Search, supports two types of searches in metabolic networks: within organism searches and synthetic pathway searches. For both types of search, the user specifies a starting and endingmetabolite of interest, and the software generates alternative reaction pathways connecting those metabolites.

• Web Omics Pop-ups: When using the Cellular Omics Viewer you can view a graph of omics data (e.g., plotting gene-expression data over time for a given gene). To do so, paint expression data on the Cellular Overview. Then mouse over a reaction (or metabolite) of interest. Click "Omics" in the menu of the resulting pop-up window, which will graph the omics data for that reaction.

• Web images: Several performance improvements were made to web images and web image generation now works on Windows-64.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• Rate-Limiting Reactions: A reaction can now be designated as rate limiting with respect to a given metabolic pathway, using the pathway editor.

• PGDB Registry Speedups: As the number of PGDBs in the registry grew, the speed of the registry became far too slow; the registry interface has been re-designed so that finding PGDBs within the registry is much faster.

• Path

  ch faster.oLogic: Pathologic can now compute abundance scores for pathways based on gene abundance values provided in input files. We have also made extensive imp

  that finding PGDBs within the registry is much faster.rovements to the name matcher that increase its sensitivity (recognition of enzyme names) with little if any decrease in its specificity.

• Metaflux: Several performance and user interface improvements were made to MetaFlux.

• New Installer: A new cross-platform installer is used for Pathway Tools.

Release Notes for BioCyc Version 16.5

Released on November 15, 2012.

Version 16.5 of BioCyc contains 2,038 Pathway/Genome Databases.

BioCyc Web Site Improvements

• Phenotype Microarrays and Other Growth Data: The displays of growth media, growth observations, and phenotype microarray data has been substantially revised.

• Atom Mappings: MetaCyc now contains atom mapping data for thousands of reactions. Atom mappings define the correspondence between atoms in the reactants of a chemical reaction, and the atoms in the products of that reaction.

• New representation of EC Numbers in Pathway Tools: Clicking on the EC number from a reaction page navigates to an EC-number page. The difference is more obvious if a reaction is associated with multiple EC numbers. In these cases all of the EC numbers, along with their names, comments, citations, etc., appear on the reaction page.

• Many Web Groups Enhancements: Many new transformations have been added/renamed.

• Customize Pathway Diagram with Omics Data: The command Pathway → Customize Pathway Diagram now includes an option for painting omics data onto an individual pathway diagram.

• Web Omics Viewer Displays Table of Pathways: The Cellular Omics Viewer (see Cellular Overview → Overlay Experimental Data) now includes an option previously present in the desktop version, namely to generate a table displaying omics data painted onto diagrams of individual pathways. This option can be selected from the "Show data:" selector in the Omics Viewer dialog.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• MetaFlux for Windows: The MetaFlux component of Pathway Tools for building steady-state metabolic flux models now runs under Windows in addition to Linux and Mac.

• Save Display State: You can now save the display state of Pathway Tools for later restoration by you or by someone you send a display-state file to.

• Captions in Cellular Omics Viewer: You can add captions for elements of the Cellular Overview diagram by right-clicking on a metabolite or a reaction and selecting Show Caption.

• Glycan Structures: Pathway Tools now supports display and editing of glycan structures.

Release Notes for BioCyc Version 16.0

Released on February 16, 2012.

Version 16.0 of BioCyc contains 1,763 Pathway/Genome Databases, including 414 complete bacterial genomes from the Human Microbiome Project.

In this release of BioCyc, our E. coli W3110 database has undergone significant enhancements under funding from the PortEco project. We performed an annotation normalization of W3110 with respect to EcoCyc (which describes strain MG1655). The purpose of this project was to modernize the annotation of W3110 with respect to the frequently updated EcoCyc annotation, and to remove spurious differences in annotations between the two strains (e.g., different protein names for proteins having the same function).

BioCyc Web Site Improvements

• Improved chemical graphics: The graphic display of chemical structures on compound and reaction pages has been re-implemented using the SVG web standard, resulting in higher quality graphics. (This improvement is currently visible only to users using recent versions of Firefox.)

• New multi-organism selector: A new multiple organism selector dialog is now available when performing comparative operations, such as using the comparative genome browser, and showing information about a given gene or pathway across multiple organisms. The new dialog is much faster and easier to use than the older selector page.

• Highlighting large groups: Previously, when painting a group (such as a gene group) to the web Cellular Overview, only short groups (of length < 100) were supported. Now this operation will work for arbitrarily long groups.

• A spelling corrector is now used during web searches.

Desktop Mode Improvements to the Downloadable Pathway Tools Software

• MetaFlux FBA Module Available on More Platforms: MetaFlux now runs on MacOS, and it runs on older versions of Linux-64 than it did previously.

Release Notes for BioCyc Version 15.5

Released on October 21, 2011.

Version 15.5 of BioCyc contains 1,700 Pathway/Genome Databases, including 414 complete bacterial genomes from the Human Microbiome Project.

The HumanCyc database has been promoted to a Tier 1 database to reflect the significant curation that HumanCyc has undergone during the last two years, and to reflect the creation of a flux-balance analysis model from HumanCyc.

BioCyc Web Site Improvements

• Web Object Groups: A web implementation of the object groups facility now exists. Users can define groups of objects of interest (such as a list of genes or metabolites), either by entering them manually or by defining groups from query results. Users can operate on web groups in a variety of ways, such as painting all objects in a group on an overview diagram, or transforming an object group (such as transforming a group of one or more genes to a group containing the one or more pathways involving those genes). Enrichment analyses can be performed on object groups (such as determining whether a gene group is over-represented for a set of pathways or a set of Gene Ontology terms). Object groups can be private, or users can share object groups with other specific users, or make them public. See Tools → Groups and the Groups Webinar.

• Taxonomic Organism Selector: The web "change organism database" dialog now provides a new mode of selecting organisms by taxonomic group; click on the "By Taxonomy" tab at the top of the selection dialog.

• Improved Nucleotide Sequence Selector: The web button "Nucleotide Sequence, Advanced" on gene/protein pages has been improved to allow specification of the desired sequence in terms of absolute coordinates as well as relative coordinates upstream and downstream of the starting gene.

• New Web Services: Web services allow Internet-based querying of BioCyc data. Several new web services have recently been added. See the appropriate section in the Website User Guide for more details.
  One application using the Pathway Tools Web services is the bioCycPlugin for Cytoscape.

• Growth Medium Search: The new command Search → Growth Media enables searching for growth media in the current PGDB according to several criteria.

• Improvements to Generic Reactions: Generic reactions in PGDBs are reactions whose classes are substrates, such as "an alcohol" and "an L-1-phosphatidyl glycerol." Improvements in the handling of generic reactions include display of such reactions on compound pages.

Improvements to Desktop BioCyc

• FBA Module Supports Gene Knock-Outs: The PTools FBA module has been extended to support prediction of growth or no-growth for single and double gene and/or reaction knock-outs. See the FBA chapter of the User's Guide for more details. This module predicts growth/no-growth for E. coli using EcoCyc with an accuracy of 86.1%.

• 64-bit Microsoft Windows Now Supported; 32-bit Windows No Longer Supported: This and future releases of Pathway Tools will support the Windows 64-bit platform; the Windows 32-bit platform will no longer be supported because memory layout issues were preventing the software from working reliably on the 32-bit platform. Operation under Windows-7 has also been improved in several respects. Please be aware of the following current limitations of the 64-bit Windows version:
  • In this version 15.5, Pathway Tools web server mode does not currently work for Windows-64. We hope to have this problem fixed for the next release or sooner.

• Growth Medium Search: The new command Tools → Search → Growth Media enables searching for growth media in the current PGDB according to several criteria.

• Improvements to Generic Reactions: Generic reactions in PGDBs are reactions whose classes are substrates, such as "an alcohol" and "an L-1-phosphatidyl glycerol." Improvements in the handling of generic reactions include display of such reactions on compound pages.

• Pathway Tools release notes
• EcoCyc release notes
• MetaCyc release notes