Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours.
Mol Syst Biol
; 8: 581, 2012 May 08.
Article
em En
| MEDLINE
| ID: mdl-22569339
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enzimas
/
Metagenoma
/
Metagenômica
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Mol Syst Biol
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOTECNOLOGIA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha