ORENZA: a web resource for studying ORphan ENZyme activities

Abstract

Background: Despite the current availability of several hundreds of thousands of amino acid sequences, more than 36% of the enzyme activities (EC numbers) defined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) are not associated with any amino acid sequence in major public databases. This wide gap separating knowledge of biochemical function and sequence information is found for nearly all classes of enzymes. Thus, there is an urgent need to explore these sequence-less EC numbers, in order to progressively close this gap.

Description: We designed ORENZA, a PostgreSQL database of ORphan ENZyme Activities, to collate information about the EC numbers defined by the NC-IUBMB with specific emphasis on orphan enzyme activities. Complete lists of all EC numbers and of orphan EC numbers are available and will be periodically updated. ORENZA allows one to browse the complete list of EC numbers or the subset associated with orphan enzymes or to query a specific EC number, an enzyme name or a species name for those interested in particular organisms. It is possible to search ORENZA for the different biochemical properties of the defined enzymes, the metabolic pathways in which they participate, the taxonomic data of the organisms whose genomes encode them, and many other features. The association of an enzyme activity with an amino acid sequence is clearly underlined, making it easy to identify at once the orphan enzyme activities. Interactive publishing of suggestions by the community would provide expert evidence for re-annotation of orphan EC numbers in public databases.

Conclusion: ORENZA is a Web resource designed to progressively bridge the unwanted gap between function (enzyme activities) and sequence (dataset present in public databases). ORENZA should increase interactions between communities of biochemists and of genomicists. This is expected to reduce the number of orphan enzyme activities by allocating gene sequences to the relevant enzymes.

Figure 1

Schema of the ORENZA relational database. The primary key of each table is in bold underlined type. Dashed arrows indicate references to foreign keys. Plain arrows represent the origin of the data stored in each table. Moreover, for the table Enzyme_activities the origin of the data is indicated by the same color code used to identify each of the following major primary databases used in our analysis: UniProt (purple), BRENDA (blue), ENZYME (green), PDB (orange) and NC-IUBMB (beige).

Figure 2

Extract from the full list of enzymes classified by the NC-IUBMB, along with their associated orphanity. For each line EC number, common name and orphanity are indicated. The total number of enzymes and the total number of orphan enzymes activities are indicated on top.

Figure 3

Details of specific enzymes. 3A: example of an enzyme entry with associated amino acid sequences. 3B: example of an orphan EC number. The fact that the enzyme is an orphan enzyme is noted after the EC number and in the Swiss-Prot and TrEMBL fields.

Figure 4

List of orphan enzyme activities for various KEGG pathways. 4A: List for pathway '01130 Lipid Metabolism', sorted by sub-pathways. 4B: List of orphan EC numbers for pathway '00564 Glycerophospholipid metabolism.'

Figure 5

Distribution of the creation year of orphan enzyme activities. 5A. Distribution during the pre-sequencing era (yellow), the gene sequencing era (pink) and the genome sequencing era (cyan). 5B Number of enzymes created within the past seven years that have/lack sequence data. Total number of EC numbers is in blue, total number of orphan EC numbers in red and percentage of orphans in green.

Figure 6

Taxonomic distribution of orphan enzyme activities. Green bars correspond to the distribution of the number of organisms (ranging from one to ten) where orphan EC numbers have been experimentally identified. In the inset, pink bars correspond to the number of orphan EC numbers identified in various ranges of number of organisms larger than ten organisms.