Conservation of the Biotin Regulon and the BirA Regulatory Signal in Eubacteria and Archaea

Rodionov, Dmitry A.; Миронов, А.; Gelfand, Mikhail S.

doi:10.1101/gr.314502

Cited by 182 publications

(234 citation statements)

References 30 publications

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“…1). Previous comparative analyses of transcription factor binding sites (3,10) proposed that many of these bioY-containing loci are members of biotin regulons.…”

Section: Resultsmentioning

confidence: 99%

“…2). Several metabolic routes seem to exist for the synthesis of the intermediate pimeloyl-CoA, which then is converted into biotin in a four-step path encoded by the universal genes bioF, bioA, bioD, and bioB (3,4). In plants, the pathway is distributed between the cytosol and the mitochondria.…”

Section: B Iotin (Vitamin H) Is An Essential Cofactor In Carboxylationmentioning

confidence: 99%

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Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Hebbeln

Rodionov

Alfandega

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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132

190

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BioMNY proteins are considered to constitute tripartite biotin transporters in prokaryotes. Recent comparative genomic and experimental analyses pointed to the similarity of BioMN to homologous modules of prokaryotic transporters mediating uptake of metals, amino acids, and vitamins. These systems resemble ATP-binding cassette-containing transporters and include typical ATPases (e.g., BioM). Absence of extracytoplasmic solute-binding proteins among the members of this group, however, is a distinctive feature. Genome context analyses uncovered that only onethird of the widespread bioY genes are linked to bioMN. Many bioY genes are located at loci encoding biotin biosynthesis, and others are unlinked to biotin metabolic or transport genes. Heterologous expression of the bioMNY operon and of the single bioY of the ␣-proteobacterium Rhodobacter capsulatus conferred biotin-transport activity on recombinant Escherichia coli cells. Kinetic analyses identified BioY as a high-capacity transporter that was converted into a high-affinity system in the presence of BioMN. BioMNY- Biotin is synthesized by many bacteria, certain archaea, fungi, and plants (reviewed in ref. 2). Several metabolic routes seem to exist for the synthesis of the intermediate pimeloyl-CoA, which then is converted into biotin in a four-step path encoded by the universal genes bioF, bioA, bioD, and bioB (3, 4). In plants, the pathway is distributed between the cytosol and the mitochondria. At least the final step, catalyzed by biotin synthase, occurs in mitochondria. This enzyme, a member of the radical SAM enzyme family, inserts a sulfur atom into dethiobiotin in a complex reaction that is linked to mitochondrial iron/sulfur metabolism (2).Biotin uptake has been analyzed in eukaryotes. In mammalian cells, the vitamin is transported across the plasma membrane by a sodium-dependent multivitamin transporter and, at least in certain tissues, by monocarboxylate transporter 1 (1). In the naturally biotin-auxotrophic yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, biotin uptake is mediated by unrelated proton symporters (5). Surprisingly little is known on the mechanisms behind biotin transport into prokaryotic cells, and multiple systems seem to exist. Active transport was observed for Escherichia coli K-12 Ͼ30 years ago (6). Despite extensive experimental work, knowledge of the complete genome sequence, and assignment of the biotin-transport locus to the 75-min genomic region, the gene(s) for the biotin transporter has not yet been identified. Recent studies by Walker and Altman (7) suggest that this system in E. coli and related Gram-negative bacteria not only transports the small vitamin, but in addition facilitates the uptake of biotinylated peptides with chain lengths up to 31 amino acid residues.In 2002, Entcheva et al. (8) reported that mutations in bioM and bioN lead to reduced biotin uptake in Sinorhizobium meliloti. Because the products of these two genes share distinct similarity with CbiO and CbiQ, which are components of prokary...

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“…1). Previous comparative analyses of transcription factor binding sites (3,10) proposed that many of these bioY-containing loci are members of biotin regulons.…”

Section: Resultsmentioning

confidence: 99%

Section: B Iotin (Vitamin H) Is An Essential Cofactor In Carboxylationmentioning

confidence: 99%

Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Hebbeln

Rodionov

Alfandega

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

132

190

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“…Biotin protein ligases all catalyze the same reaction and their sequences are highly conserved across evolution. However, sequence comparison of bacterial BPLs, including those from eubacteria and archaebacteria, reveals that only a subset are both enzymes and transcriptional repressors (34). For example, Pyrococcus horikoshii encodes a monofunctional ligase, which does not contain an N-terminal DNA binding domain and therefore does not bind to DNA.…”

Section: Discussionmentioning

confidence: 99%

Nucleation of an Allosteric Response via Ligand-induced Loop Folding

Naganathan

Beckett

2007

Journal of Molecular Biology

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The Escherichia coli biotin repressor, BirA, is an allosteric transcription regulatory protein to which binding of the small ligand corepressor, biotinyl-5'-AMP, promotes homodimerization and subsequent DNA binding. Structural data indicate that the apo-or unliganded repressor is characterized by four partially disordered loops that are ordered in the ligand-bound dimer. While three of these loops participate directly in the dimerization, the fourth, consisting of residues 212-234 is distal to the interface. This loop, which is ordered around the adenine ring of the adenylate in the BirA adenylate structure, is referred to as the adenylate binding loop or ABL. Although residues in the loop do not directly interact with the ligand, a hydrophobic cluster consisting of a tryptophan and two valine side chains assembles over the adenine base. Results of previous measurements suggest that folding of the ABL is integral to the allosteric response. This idea and the role of the hydrophobic cluster in the process were investigated by systematic replacement of each side chain in the cluster with alanine and analysis of the variant proteins for small ligand binding and dimerization. Isothermal titration calorimetry measurements indicate defects in adenylate binding for all ABL variants. Additionally, sedimentation equilibrium measurements reveal that coupling between adenylate binding and dimerization is compromised in each mutant. Partial proteolysis measurements indicate that the mutants are defective in ligand-linked folding of the ABL. These results indicate that the hydrophobic cluster is critical to the ligand-induced disorder-to-order transition in the ABL and that this transition is integral to the allosteric response in the biotin repressor.

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“…The lack of modules mapping to traditional pathways in the central metabolism suggests high diversity in its structure and evolution in different bacteria as well as the complexity of its regulation [e.g., a cascade of 11 transcription factors regulating three genes, aslL, zwf, and gnd, in the pentose phosphate pathway (28) Although observed differences between pathways and modules could not be systematically explained by gene regulation, pathways coregulated in E. coli tend to cluster into modules more than do pathways without a common regulator. We observe this tendency in biosynthetic pathways (e.g., modular arginine, branched chain and aromatic amino acids, histidine, threonine and lysine, and methionine pathways vs. nonmodular glutamine͞ glutamate, asparagine͞aspartate, serine and glycine, and proline pathways) and vitamin biosynthetic pathways [modular biotin pathway regulated by BirA vs. other vitamin pathways, such as riboflavin and thiamin (30)(31)(32)(33)(34)]. In the same vein, we notice that purB, the gene breaking the purine biosynthesis pathway, is regulated in a unique way, by a transcription roadblock mechanism with the binding site for the PurR repressor deep within the coding region (35).…”

Section: The Network Contains Several Evolutionary and Regulatory Metmentioning

confidence: 99%

A metabolic network in the evolutionary context: Multiscale structure and modularity

Spirin

Gelfand

Mironov

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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The enormous complexity of biological networks has led to the suggestion that networks are built of modules that perform particular functions and are ''reused'' in evolution in a manner similar to reusable domains in protein structures or modules of electronic circuits. Analysis of known biological networks has revealed several modules, many of which have transparent biological functions. However, it remains to be shown that identified structural modules constitute evolutionary building blocks, independent and easily interchangeable units. An alternative possibility is that evolutionary modules do not match structural modules. To investigate the structure of evolutionary modules and their relationship to functional ones, we integrated a metabolic network with evolutionary associations between genes inferred from comparative genomics. The resulting metabolic-genomic network places metabolic pathways into evolutionary and genomic context, thereby revealing previously unknown components and modules. We analyzed the integrated metabolic-genomic network on three levels: macro-, meso-, and microscale. The macroscale level demonstrates strong associations between neighboring enzymes and between enzymes that are distant on the network but belong to the same linear pathway. At the mesoscale level, we identified evolutionary metabolic modules and compared them with traditional metabolic pathways. Although, in some cases, there is almost exact correspondence, some pathways are split into independent modules. On the microscale level, we observed high association of enzyme subunits and weak association of isoenzymes independently catalyzing the same reaction. This study shows that evolutionary modules, rather than pathways, may be thought of as regulatory and functional units in bacterial genomes.clustering ͉ evolution ͉ modules R ecent studies of biological networks have revealed structural modules and ubiquitous motifs, many of which have transparent biological functions. However, it remains to be shown that identified structural modules constitute evolutionary building blocks, independent and easily interchangeable units. An alternative possibility is that evolutionary modules do not match structural modules. Comparative genomics and analysis of biological networks provide tools to address this question. Here, we study one of the most accurately assembled networks, the metabolic network of Escherichia coli. To reveal evolutionary modules, we integrate metabolic network with evolutionary associations between genes inferred by comparative genomics of multiple bacterial species. Two genes are associated if (i) they have conserved proximity in distantly related genomes; and͞or (ii) demonstrate co-occurrence (i.e., both present or both absent) in most genomes; and͞or (iii) have been found fused together. The frequency of these events provides a measure of evolutionary association between the genes. We combine this measure with the structure of the metabolic network to identify evolutionary modules as regions of the network tha...

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Conservation of the Biotin Regulon and the BirA Regulatory Signal in Eubacteria and Archaea

Cited by 182 publications

References 30 publications

Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Biotin uptake in prokaryotes by solute transporters with an optional ATP-binding cassette-containing module

Nucleation of an Allosteric Response via Ligand-induced Loop Folding

A metabolic network in the evolutionary context: Multiscale structure and modularity

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