ArticleMolecular systems biology2012
Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- DeepES: deep learning-based enzyme screening to identify orphan enzyme genes.Bioinformatics (Oxford, England) · 2025Article
- Biosynthesis ofACS chemical biology · 2024Article
- Implementation of homology based and non-homology based computational methods for the identification and annotation of orphan enzymes: using Mycobacterium tuberculosis H37Rv as a case study.BMC bioinformatics · 2020Article
- Targeted enzyme gene re-positioning: A computational approach for discovering alternative bacterial enzymes for the synthesis of plant-specific secondary metabolites.Metabolic engineering communications · 2019Article
- Creation and analysis of biochemical constraint-based models using the COBRA Toolbox v.3.0.Nature protocols · 2019Article
- Missing gene identification using functional coherence scores.Scientific reports · 2016Article
- Metabolic pathway reconstruction strategies for central metabolism and natural product biosynthesis.Biophysics and physicobiology · 2016Review
- A new network representation of the metabolism to detect chemical transformation modules.BMC bioinformatics · 2015Article
- DomSign: a top-down annotation pipeline to enlarge enzyme space in the protein universe.BMC bioinformatics · 2015Article
- Consistency Analysis of Genome-Scale Models of Bacterial Metabolism: A Metamodel Approach.PloS one · 2015Article
- Metagenomics: tools and insights for analyzing next-generation sequencing data derived from biodiversity studies.Bioinformatics and biology insights · 2015Review
- Leveraging structure for enzyme function prediction: methods, opportunities, and challenges.Trends in biochemical sciences · 2014Review
- Profiling the orphan enzymes.Biology direct · 2014Review
- Merging metagenomics and geochemistry reveals environmental controls on biological diversity and evolution.BMC ecology · 2014Article
- Interactions in the microbiome: communities of organisms and communities of genes.FEMS microbiology reviews · 2014Review
- Finding sequences for over 270 orphan enzymes.PloS one · 2014Article
- Solving gap metabolites and blocked reactions in genome-scale models: application to the metabolic network of Blattabacterium cuenoti.BMC systems biology · 2013Article
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Authors and funding
10 authors.
Funding
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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.
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