|
type |
Journal Article |
authors |
Yamada T, Waller AS, Raes J, Zelezniak A, Perchat N, Perret A, Salanoubat M, Patil KR, Weissenbach J, Bork P |
title |
Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours |
journal |
Mol Syst Biol |
Activity |
2.6.1.38 |
sel |
selected |
ui |
22569339 |
year |
(2012) |
volume |
8 |
pages |
581 |
| |
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. |
last changed |
2018/03/08 11:50 |
|