title: A new family of enzymes catalyzing the first committed step of the methylerythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in bacteria.
abstract: Isoprenoids are a large family of compounds with essential functions in all domains of life. Most eubacteria synthesize their isoprenoids using the methylerythritol 4-phosphate (MEP) pathway, whereas a minority uses the unrelated mevalonate pathway and only a few have both. Interestingly, Brucella abortus and some other bacteria that only use the MEP pathway lack deoxyxylulose 5-phosphate (DXP) reductoisomerase (DXR), the enzyme catalyzing the NADPH-dependent production of MEP from DXP in the first committed step of the pathway. Fosmidomycin, a specific competitive inhibitor of DXR, inhibited growth of B. abortus cells expressing the Escherichia coli GlpT transporter (required for fosmidomycin uptake), confirming that a DXR-like (DRL) activity exists in these bacteria. The B. abortus DRL protein was found to belong to a family of uncharacterized proteins similar to homoserine dehydrogenase. Subsequent experiments confirmed that DRL and DXR catalyze the same biochemical reaction. DRL homologues shown to complement a DXR-deficient E. coli strain grouped within the same phylogenetic clade. The scattered taxonomic distribution of sequences from the DRL clade and the occurrence of several paralogues in some bacterial strains might be the result of lateral gene transfer and lineage-specific gene duplications and/or losses, similar to that described for typical mevalonate and MEP pathway genes. These results reveal the existence of a novel class of oxidoreductases catalyzing the conversion of DXP into MEP in prokaryotic cells, underscoring the biochemical and genetic plasticity achieved by bacteria to synthesize essential compounds such as isoprenoids.
authors.affiliation: Departamento de Biología Molecular, Universidad de Cantabria and Instituto de Biomedicina y Biotecnologia de Cantabria (IBBTEC), CSIC-UC-IDICAN, 39011 Santander, Spain. sangarif@unican.es
authors.forename: Félix J
authors.initials: FJ
authors.lastname: Sangari
authors.forename: Jordi
authors.initials: J
authors.lastname: Pérez-Gil
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Carretero-Paulet
authors.forename: Juan M
authors.initials: JM
authors.lastname: García-Lobo
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Concepción
mesh_terms: D019747:Aldose-Ketose Isomerases / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism*; D004798:Enzymes; D004896:Erythritol / Q000031:analogs & derivatives* / Q000378:metabolism; D053858:Metabolic Networks and Pathways; D009097:Multienzyme Complexes / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D010428:Pentosephosphates / Q000378:metabolism; D013403:Sugar Phosphates / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism*
chemical_list: C109460:1-deoxylulose 5-phosphate; C114232:2-C-methylerythritol 4-phosphate; D004798:Enzymes; D009097:Multienzyme Complexes; D010428:Pentosephosphates; D013403:Sugar Phosphates; D013729:Terpenes; D010088:Oxidoreductases; C114231:1-deoxy-D-xylulose 5-phosphate reductoisomerase; D019747:Aldose-Ketose Isomerases; D004896:Erythritol