Mutations in escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway

A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phospha...

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Detalhes bibliográficos
Autores: Perez Gil, Jordi, Uros, Eva Maria, Sauret-Güeto, Susanna, Lois Rojas, Luisa María, Kirby, James, Nishimoto, Minobu, Baidoo, Edward E.K., Keasling, Jay D., Boronat i Margosa, Albert, Rodríguez Concepción, Manuel
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2012
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/127789
Acesso em linha:https://hdl.handle.net/2445/127789
Access Level:Acceso aberto
Palavra-chave:Escheríchia coli
Genètica
Metabolisme
Fisiologia
Proteïnes
Mutació (Biologia)
Transferases
Escherichia coli
Genetics
Metabolism
Physiology
Proteins
Mutation (Biology)
Descrição
Resumo:A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.