Puzzling over orphan enzymes

Lespinet, Olivier; Labedan, Bernard

doi:10.1007/s00018-005-5520-6

Cited by 20 publications

(17 citation statements)

References 33 publications

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“…In KEGG and MetaCyc, there are 4,588 and 4,497 reactions not linked to a complete EC number, respectively. As a consequence and as noted previously [12,27], the percentage of orphan enzymes may be underestimated using only the EC classification. It increases considerably when the estimation is made at the reaction level using metabolic resources: in KEGG and MetaCyc, 48% and 39% of the reactions are lacking associated protein or nucleic sequences, respectively.…”

Section: Reviewsupporting

confidence: 53%

Profiling the orphan enzymes

et al. 2014

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The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new activities.ReviewersThis article was reviewed by Michael Galperin, Daniel Haft and Daniel Kahn.

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Section: Reviewsupporting

confidence: 53%

Profiling the orphan enzymes

et al. 2014

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“…According to a recent survey, the number of different orphan enzymes exceeds fifteen hundred, i.e. more than 39% of the known enzymatic activities [81]. …”

Section: Resultsmentioning

confidence: 99%

High precision multi-genome scale reannotation of enzyme function by EFICAz

2006

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“…CMT1 can be classified as an orphan enzyme since its enzyme activity has not been associated with any sequence deposited in major public databases. This is not an uncommon situation, since more than 39% of the well-defined enzyme activities (EC numbers) are not linked to any DNA sequence (Lespinet and Labedan, 2006). However, this percentage is increasing very quickly as a result of the sequencing of numerous genomes.…”

Section: Discussionmentioning

confidence: 95%