Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway
Pérez-Gil, Jordi (Centre de Recerca en Agrigenòmica)
Uros, Eva Maria (Centre de Recerca en Agrigenòmica)
Sauret-Güeto, Susanna (Centre de Recerca en Agrigenòmica)
Lois, L. Maria (Centre de Recerca en Agrigenòmica)
Kirby, James (Joint BioEnergy Institute)
Nishimoto, Minobu (Joint BioEnergy Institute)
Baidoo, Edward E. K. (Joint BioEnergy Institute)
Keasling, Jay D. (Joint BioEnergy Institute)
Boronat i Margosa, Albert (Centre de Recerca en Agrigenòmica)
Rodríguez Concepción, Manuel (Centre de Recerca en Agrigenòmica)

Date:	2012
Abstract:	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.
Grants:	Ministerio de Ciencia e Innovación BIO2011-23680 Ministerio de Ciencia e Innovación BIO2009-09523
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 7, issue 8 (Aug. 2012) , e43775, ISSN 1932-6203

DOI: 10.1371/journal.pone.0043775
PMID: 22928031

6 p, 558.0 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Experimental sciences > CRAG (Centre for Research in Agricultural Genomics)
Articles > Research articles
Articles > Published articles