BRENDA, the ELIXIR core data resource in 2021: new developments and updates

Abstract

The BRENDA enzyme database (https://www.brenda-enzymes.org), established in 1987, has evolved into the main collection of functional enzyme and metabolism data. In 2018, BRENDA was selected as an ELIXIR Core Data Resource. BRENDA provides reliable data, continuous curation and updates of classified enzymes, and the integration of newly discovered enzymes. The main part contains >5 million data for ∼90 000 enzymes from ∼13 000 organisms, manually extracted from ∼157 000 primary literature references, combined with information of text and data mining, data integration, and prediction algorithms. Supplements comprise disease-related data, protein sequences, 3D structures, genome annotations, ligand information, taxonomic, bibliographic, and kinetic data. BRENDA offers an easy access to enzyme information from quick to advanced searches, text- and structured-based queries for enzyme-ligand interactions, word maps, and visualization of enzyme data. The BRENDA Pathway Maps are completely revised and updated for an enhanced interactive and intuitive usability. The new design of the Enzyme Summary Page provides an improved access to each individual enzyme. A new protein structure 3D viewer was integrated. The prediction of the intracellular localization of eukaryotic enzymes has been implemented. The new EnzymeDetector combines BRENDA enzyme annotations with protein and genome databases for the detection of eukaryotic and prokaryotic enzymes.

The Metano Modeling Toolbox MMTB: An Intuitive, Web-Based Toolbox Introduced by Two Use Cases

“…Metano Modeling Toolbox (MMTB) is a web-based tool for the generation and analysis of metabolic models. MMTB closes the gap between BKMS-react [39] and EnzymeDetector [40,41]: biochemical reactions from BKMS-react are associated with genome annotations from EnzymeDetector and preprocessed for use in metabolic modeling. Information on metabolite structures and synonyms and the assembly of reactions into pathways support bottom-up model generation.…”

“…The user can search for reactions by either entering parts of the biochemical reaction, EC numbers, database IDs, or by selecting a BRENDA, MetaCyc, or KEGG pathway. The resulting reactions originate from the integrative database BKMS-react [39] that includes all reactions from BRENDA [41], KEGG [42], MetaCyc [43], and SABIO-RK [44]. MMTB shows ready-to-use reactions and further information, e.g., the assigned EC numbers, database IDs, associated pathways, and further links.…”

“…When the user selects an organism from a dropdown list, MMTB displays a confidence score for the annotation of each enzymatic reaction. This score comes from EnzymeDetector, which integrates genome annotations from different resources [41]. All reactions can be downloaded in a plain reaction file for use with the Metano command-line tool.…”

“…The model was built bottom-up using the pathway search of MMTB. All pathways for biomass production and degradation of various carbon sources were checked using the built-in genome annotation score from EnzymeDetector [41]. We included all necessary pathways into the model and matched gene locus tags using the UniProt accessions that were given by MMTB (Supplementary Table S1).…”

BENZ WS: the Bologna ENZyme Web Server for four-level EC number annotation

“…Other databases, by integrating different sources of information, comprising UniProt and PDB, offer a complete annotation for enzymes, such as BRENDA, ( 12 ), ( https://www.brenda-enzymes.org/index.php ) and CATH ( https:// http://www.cathdb.info/ ) ( 13 ). BRENDA, established in 1987, has evolved into a main collection of curated functional enzyme and metabolism data, supported by links to literature and continuously updating ( 12 ). CATH, in turn, is a free, publicly available online resource that provides information on the evolutionary relationships of protein domains.…”