Comparative genomics of bacterial and plant folate synthesis and salvage: predictions and validations

Abstract

BackgroundFolate 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.ResultsBased 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.ConclusionFor 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.

Moonlighting Glutamate Formiminotransferases Can Functionally Replace 5-Formyltetrahydrofolate Cycloligase

“…It might therefore be expected that all organisms would have 5-FCL, except those few that lack SHMT (14) or folates (15). However, in the course of a comparative genomic analysis of folate synthesis and metabolism involving hundreds of genomes (16) we were surprised to note that diverse prokaryotes had genes encoding SHMT (glyA) and other folate-dependent enzymes but no gene for .…”

“…where there is either a completely different enzyme (nonorthologous displacement) or an alternative pathway (16,17). Here, we report an investigation of these possibilities using comparative genomics analysis.…”

Characterization of fermented broccoli (Brassica oleraceaL.) and spinach (Amaranthussp.) produced using microfiltration membrane as folic acid source for smart food formula

“…will make this commodity as alternative resource of natural folic acid. Polyphenols contained in broccoli and spinach are source of folic acid produced by activity of microbes in Kombucha culture through de novo biosynthesis [5] in amino acids (adenine, hisyidine, methionine) from Kombucha culture (fungi, bacteria, yeast) and tea leaves.…”

“…This biosynthesis involves enzyme activities of dihydrofolate synthase (DHFS) and ypolyglutamate synthease (FPGS) to form dihydrofolate and polyglutamate folate, a derivative of folic acid [5], in which this process is occurred only on plant and microbe [6]. Kombucha cultures containing Acetic Acid Bacteria, such as Acetobacter xylinum and yeast, such as Saccharomyces cereviseae, Saccharomyces ludwigii, Saccharomyces bisporus, Zygosaccharomyces sp.…”

Estudos estruturais de enzimas da via de biossíntese de folatos de <i>Xanthomonas albilineans</i> para o desenvolvimento de novos candidatos a agroquímicos para a cultura de cana-de-açúcar

“…Fonte: Adaptada de de CRÉCY-LAGARD et al 58 Além das enzimas DHPS e DHFR, para as quais diversos fármacos foram desenvolvidos, outras enzimas da via dos folatos podem constituir alvos moleculares para o desenvolvimento de novos inibidores. Uma vez que análogos estruturais do substrato podem atuar em múltiplas enzimas da mesma cascata metabólica, 54 levando à inibição enzimática simultânea, maior eficácia do tratamento e diminuição da resistência bacteriana, a caracterização estrutural e funcional de todas as enzimas de uma via biossintética já validada é uma estratégia interessante na busca por novas substâncias inibidoras.…”