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Title: Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours
Authors: Yamada, Takuji ×
Waller, Alison S
Raes, Jeroen
Zelezniak, Aleksej
Perchat, Nadia
Perret, Alain
Salanoubat, Marcel
Patil, Kiran R
Weissenbach, Jean
Bork, Peer #
Issue Date: May-2012
Publisher: Nature Pub. Group
Series Title: Molecular Systems Biology vol:8 pages:581
Article number: 10.1038/msb.2012.13
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.
URI: 
ISSN: 1744-4292
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Non-KU Leuven Association publications
× corresponding author
# (joint) last author

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