ReviewThe Biochemical journal2009
'Unknown' proteins and 'orphan' enzymes: the missing half of the engineering parts list--and how to find it.
Review in The Biochemical journal, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
113 citing papers in PubMed.
- Impacts of feeding preweaned calves milk containing drug residues on the functional profile of the fecal microbiota.Scientific reports · 2018Trial
- ThebioRxiv : the preprint server for biology · 2026Article
- Reverse prediction of carbohydrate esterase polysaccharide targets.Biotechnology for biofuels and bioproducts · 2026Article
- Systematic discovery of enzyme promiscuity in Escherichia coli using in vitro metabolomics.Communications biology · 2026Article
- The transformative power of structural predictions with AI in plant science.The Plant journal : for cell and molecular biology · 2026Review
- Article
- Limitations of current machine learning models in predicting enzymatic functions for uncharacterized proteins.G3 (Bethesda, Md.) · 2025Article
- Using bioinformatics for identifying and plugging metabolic pathway holes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- C11orf54 catalyzes L-xylulose formation in human metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Predicting Protein Function in the AI and Big Data Era.Biochemistry · 2025Review
- Charting unknown metabolic reactions by mass spectrometry-resolved stable-isotope tracing metabolomics.Nature communications · 2025Article
- Artificial intelligence-based prediction of pathogen emergence and evolution in the world of synthetic biology.Microbial biotechnology · 2024Review
- GlobalNature metabolism · 2024Article
- Assembling bacterial puzzles: piecing together functions into microbial pathways.NAR genomics and bioinformatics · 2024Article
- The Y-ome Conundrum: Insights into Uncharacterized Genes and Approaches for Functional Annotation.Molecular and cellular biochemistry · 2024Review
- Biosynthesis and function of 7-deazaguanine derivatives in bacteria and phages.Microbiology and molecular biology reviews : MMBR · 2024Review
- Understanding the gut microbiota by considering human evolution: a story of fire, cereals, cooking, molecular ingenuity, and functional cooperation.Microbiology and molecular biology reviews : MMBR · 2024Review
- Detecting anomalous proteins using deep representations.NAR genomics and bioinformatics · 2024Article
- Identification and preliminary characterization of conserved uncharacterized proteins fromPlant direct · 2023Article
- Integrative Approach to Probe Alternative Redox Mechanisms in RNA Modifications.Accounts of chemical research · 2023Article
53 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Like other forms of engineering, metabolic engineering requires knowledge of the components (the 'parts list') of the target system. Lack of such knowledge impairs both rational engineering design and diagnosis of the reasons for failures; it also poses problems for the related field of metabolic reconstruction, which uses a cell's parts list to recreate its metabolic activities in silico. Despite spectacular progress in genome sequencing, the parts lists for most organisms that we seek to manipulate remain highly incomplete, due to the dual problem of 'unknown' proteins and 'orphan' enzymes. The former are all the proteins deduced from genome sequence that have no known function, and the latter are all the enzymes described in the literature (and often catalogued in the EC database) for which no corresponding gene has been reported. Unknown proteins constitute up to about half of the proteins in prokaryotic genomes, and much more than this in higher plants and animals. Orphan enzymes make up more than a third of the EC database. Attacking the 'missing parts list' problem is accordingly one of the great challenges for post-genomic biology, and a tremendous opportunity to discover new facets of life's machinery. Success will require a co-ordinated community-wide attack, sustained over years. In this attack, comparative genomics is probably the single most effective strategy, for it can reliably predict functions for unknown proteins and genes for orphan enzymes. Furthermore, it is cost-efficient and increasingly straightforward to deploy owing to a proliferation of databases and associated tools.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.