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| Item Type: | Article |
|---|---|
| Title: | Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours |
| Creators Name: | Yamada, T., Waller, A.S., Raes, J., Zelezniak, A., Perchat, N., Perret, A., Salanoubat, M., Patil, K.R., Weissenbach, J. and Bork, P. |
| Abstract: | Despite the current wealth of sequencing data, one-third of all biochemically characterized metabolic enzymes lack a corresponding gene or protein sequence, and as such can be considered orphan enzymes. They represent a major gap between our molecular and biochemical knowledge, and consequently are not amenable to modern systemic analyses. As 555 of these orphan enzymes have metabolic pathway neighbours, we developed a global framework that utilizes the pathway and (meta)genomic neighbour information to assign candidate sequences to orphan enzymes. For 131 orphan enzymes (37% of those for which (meta)genomic neighbours are available), we associate sequences to them using scoring parameters with an estimated accuracy of 70%, implying functional annotation of 16,345 gene sequences in numerous (meta)genomes. As a case in point, two of these candidate sequences were experimentally validated to encode the predicted activity. In addition, we augmented the currently available genome-scale metabolic models with these new sequence-function associations and were able to expand the models by on average 8%, with a considerable change in the flux connectivity patterns and improved essentiality prediction. |
| Keywords: | Genomics, Metabolic Pathways, Metagenomics, Neighbourhood Information, Orphan Enzymes |
| Source: | Molecular Systems Biology |
| ISSN: | 1744-4292 |
| Publisher: | Nature Publishing Group |
| Volume: | 8 |
| Page Range: | 581 |
| Date: | 8 May 2012 |
| Official Publication: | https://doi.org/10.1038/msb.2012.13 |
| PubMed: | View item in PubMed |
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