Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours

Yamada, T.; Waller, A.S.; Raes, J.; Zelezniak, A.; Perchat, N.; Perret, A.; Salanoubat, M.; Patil, K.R.; Weissenbach, J.; Bork, P.

Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours

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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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