title: Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validations.
abstract: BACKGROUND
  Folate synthesis and salvage pathways are relatively well known from classical biochemistry and genetics but they have not been subjected to comparative genomic analysis. The availability of genome sequences from hundreds of diverse bacteria, and from Arabidopsis thaliana, enabled such an analysis using the SEED database and its tools. This study reports the results of the analysis and integrates them with new and existing experimental data.
  
  
  RESULTS
  Based on sequence similarity and the clustering, fusion, and phylogenetic distribution of genes, several functional predictions emerged from this analysis. For bacteria, these included the existence of novel GTP cyclohydrolase I and folylpolyglutamate synthase gene families, and of a trifunctional p-aminobenzoate synthesis gene. For plants and bacteria, the predictions comprised the identities of a 'missing' folate synthesis gene (folQ) and of a folate transporter, and the absence from plants of a folate salvage enzyme. Genetic and biochemical tests bore out these predictions.
  
  
  CONCLUSIONS
  For bacteria, these results demonstrate that much can be learnt from comparative genomics, even for well-explored primary metabolic pathways. For plants, the findings particularly illustrate the potential for rapid functional assignment of unknown genes that have prokaryotic homologs, by analyzing which genes are associated with the latter. More generally, our data indicate how combined genomic analysis of both plants and prokaryotes can be more powerful than isolated examination of either group alone.
authors.affiliation: Department of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA. vcrecy@ufl.edu
authors.forename: Valérie
authors.initials: V
authors.lastname: de Crécy-Lagard
authors.forename: Basma
authors.initials: B
authors.lastname: El Yacoubi
authors.forename: Rocío Díaz
authors.initials: RD
authors.lastname: de la Garza
authors.forename: Alexandre
authors.initials: A
authors.lastname: Noiriel
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Hanson
mesh_terms: D027321:Anion Transport Proteins; D001419:Bacteria / Q000235:genetics* / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism*; D006136:GTP Cyclohydrolase / Q000235:genetics; D023281:Genomics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D010453:Peptide Synthases / Q000235:genetics; D010944:Plants / Q000235:genetics* / Q000378:metabolism*; D011624:Pteroylpolyglutamic Acids / Q000378:metabolism; D000637:Transaminases / Q000235:genetics
chemical_list: D027321:Anion Transport Proteins; D011624:Pteroylpolyglutamic Acids; D005492:Folic Acid; C022309:PABA synthase; D000637:Transaminases; D006136:GTP Cyclohydrolase; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase