Systematic discovery of analogous enzymes in thiamin biosynthesis.
Nat Biotechnol
; 21(7): 790-5, 2003 Jul.
Article
em En
| MEDLINE
| ID: mdl-12794638
In all genome-sequencing projects completed to date, a considerable number of 'gaps' have been found in the biochemical pathways of the respective species. In many instances, missing enzymes are displaced by analogs, functionally equivalent proteins that have evolved independently and lack sequence and structural similarity. Here we fill such gaps by analyzing anticorrelating occurrences of genes across species. Our approach, applied to the thiamin biosynthesis pathway comprising approximately 15 catalytic steps, predicts seven instances in which known enzymes have been displaced by analogous proteins. So far we have verified four predictions by genetic complementation, including three proteins for which there was no previous experimental evidence of a role in the thiamin biosynthesis pathway. For one hypothetical protein, biochemical characterization confirmed the predicted thiamin phosphate synthase (ThiE) activity. The results demonstrate the ability of our computational approach to predict specific functions without taking into account sequence similarity.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiamina
/
Alinhamento de Sequência
/
Alquil e Aril Transferases
/
Metabolismo Energético
/
Escherichia coli
/
Modelos Biológicos
Tipo de estudo:
Evaluation_studies
/
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Biotechnol
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
México
País de publicação:
Estados Unidos