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emergence and modular evolution of a novel motility machinery in bacteria.bacteria glide across solid surfaces by mechanisms that have remained largely mysterious despite decades of research. in the deltaproteobacterium myxococcus xanthus, this locomotion allows the formation stress-resistant fruiting bodies where sporulation takes place. however, despite the large number of genes identified as important for gliding, no specific machinery has been identified so far, hampering in-depth investigations. based on the premise that components of the gliding machinery must h ...201121931562
discovery and total synthesis of a new estrogen receptor heterodimerizing actinopolymorphol a from actinopolymorpha rutilus.estrogen receptor eralpha and erbeta heterodimerization has been implicated in cancer chemoprevention. the discovery, structural elucidation, and total synthesis of a new natural product, actinopolymorphol a (1), from actinopolymorpha rutilus (yim45725) that preferentially induces eralpha/beta heterodimerization is reported. total synthesis of 1 has allowed us to determine its absolute stereochemistry and that of a previously known deacetylated congener, and 1 represents the first member of a ne ...201020593804
A novel cyanophage with a cyanobacterial nonbleaching protein a gene in the genome.A cyanophage, PaV-LD, has been isolated from harmful filamentous cyanobacterium Planktothrix agardhii in Lake Donghu, a shallow freshwater lake in China. Here, we present the cyanophage's genomic organization and major structural proteins. The genome is a 95,299-bp-long, linear double-stranded DNA and contains 142 potential genes. BLAST searches revealed 29 proteins of known function in cyanophages, cyanobacteria, or bacteria. Thirteen major structural proteins ranging in size from 27 kDa to 172 ...201222031930
Is the sequence-specific binding of aminoacyl-tRNAs by EF-Tu universal among bacteria?Three base pairs in the T-stem are primarily responsible for the sequence-specific interaction of tRNA with Escherichia coli and Thermus thermophilus EF-Tu. While the amino acids on the surface of EF-Tu that contact aminoacyl-tRNA (aa-tRNA) are highly conserved among bacteria, the T-stem sequences of individual tRNA are variable, making it unclear whether or not this protein-nucleic acid interaction is also sequence specific in other bacteria. We propose and validate a thermodynamic model that p ...201121893586
structural insights into the function of aminoglycoside-resistance a1408 16s rrna methyltransferases from antibiotic-producing and human pathogenic bacteria.x-ray crystal structures were determined of the broad-spectrum aminoglycoside-resistance a1408 16s rrna methyltransferases kamb and npma, from the aminoglycoside-producer streptoalloteichus tenebrarius and human pathogenic escherichia coli, respectively. consistent with their common function, both are class i methyltransferases with additional highly conserved structural motifs that embellish the core sam-binding fold. in overall structure, the a1408 rrna methyltransferase were found to be most ...201020639535
marine myxobacteria as a source of antibiotics--comparison of physiology, polyketide-type genes and antibiotic production of three new isolates of enhygromyxa salina.three myxobacterial strains, designated swb004, swb005 and swb006, were obtained from beach sand samples from the pacific ocean and the north sea. the strains were cultivated in salt water containing media and subjected to studies to determine their taxonomic status, the presence of genes for the biosynthesis of polyketides and antibiotic production. 16s rdna sequence analysis revealed the type strain enhygromyxa salina shk-1(t) as their closest homolog, displaying between 98% (swb005) and 99% ( ...201020948900
complete genome sequence of marinomonas posidonica type strain (ivia-po-181(t)).marinomonas posidonica ivia-po-181(t) lucas-elío et al. 2011 belongs to the family oceanospirillaceae within the phylum proteobacteria. different species of the genus marinomonas can be readily isolated from the seagrass posidonia oceanica. m. posidonica is among the most abundant species of the genus detected in the cultured microbiota of p. oceanica, suggesting a close relationship with this plant, which has a great ecological value in the mediterranean sea, covering an estimated surface of 38 ...201223458837
Gating NO Release from Nitric Oxide Synthase.We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV-vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for ...201122148177
annotation of protein domains reveals remarkable conservation in the functional make up of proteomes across superkingdoms.the functional repertoire of a cell is largely embodied in its proteome, the collection of proteins encoded in the genome of an organism. the molecular functions of proteins are the direct consequence of their structure and structure can be inferred from sequence using hidden markov models of structural recognition. here we analyze the functional annotation of protein domain structures in almost a thousand sequenced genomes, exploring the functional and structural diversity of proteomes. we find ...201124710297
isolation of xylose isomerases by sequence- and function-based screening from a soil metagenome library.abstract: background: xylose isomerase (xi) catalyses the isomerization of xylose to xylulose in bacteria and some fungi. currently, only a limited number of xi genes have been functionally expressed in saccharomyces cerevisiae, the microorganism of choice for lignocellulosic ethanol production. the objective of the present study was to search for novel xi genes in the vastly diverse microbial habitat present in soil. as the exploitation of microbial diversity is impaired by the ability to culti ...201121545702
thermostable direct hemolysin downregulates human colon carcinoma cell proliferation with the involvement of e-cadherin, and β-catenin/tcf-4 signaling.colon cancers are the frequent causes of cancer mortality worldwide. recently bacterial toxins have received marked attention as promising approaches in the treatment of colon cancer. thermostable direct hemolysin (tdh) secreted by vibrio parahaemolyticus causes influx of extracellular calcium with the subsequent rise in intracellular calcium level in intestinal epithelial cells and it is known that calcium has antiproliferative activity against colon cancer.201121625458
evolution of dna ligases of nucleo-cytoplasmic large dna viruses of eukaryotes: a case of hidden complexity.eukaryotic nucleo-cytoplasmic large dna viruses (ncldv) encode most if not all of the enzymes involved in their dna replication. it has been inferred that genes for these enzymes were already present in the last common ancestor of the ncldv. however, the details of the evolution of these genes that bear on the complexity of the putative ancestral ncldv and on the evolutionary relationships between viruses and their hosts are not well understood.200920021668
horizontal gene transfer of zinc and non-zinc forms of bacterial ribosomal protein s4.the universal ribosomal protein s4 is essential for the initiation of small subunit ribosomal assembly and translational accuracy. being part of the information processing machinery of the cell, the gene for s4 is generally thought of as being inherited vertically and has been used in concatenated gene phylogenies. here we report the evolution of ribosomal protein s4 in relation to a broad sharing of zinc/non-zinc forms of the gene and study the scope of horizontal gene transfer (hgt) of s4 duri ...200919640295
presence of a classical rrm-fold palm domain in thg1-type 3'- 5'nucleic acid polymerases and the origin of the ggdef and crispr polymerase domains.almost all known nucleic acid polymerases catalyze 5'-3' polymerization by mediating the attack on an incoming nucleotide 5' triphosphate by the 3'oh from the growing polynucleotide chain in a template dependent or independent manner. the only known exception to this rule is the thg1 rna polymerase that catalyzes 3'-5' polymerization in vitro and also in vivo as a part of the maturation process of histidinyl trna. while the initial reaction catalyzed by thg1 has been compared to adenylation cata ...201020591188
metagenomic analysis of a southern maritime antarctic soil.our current understanding of antarctic soils is derived from direct culture on selective media, biodiversity studies based on clone library construction and analysis, quantitative pcr amplification of specific gene sequences and the application of generic microarrays for microbial community analysis. here, we investigated the biodiversity and functional potential of a soil community at mars oasis on alexander island in the southern maritime antarctic, by applying 454 pyrosequencing technology to ...201223227023
analysis of genome content evolution in pvc bacterial super-phylum: assessment of candidate genes associated with cellular organization and lifestyle.the planctomycetes, verrucomicrobia, chlamydiae (pvc) super-phylum contains bacteria with either complex cellular organization or simple cell structure; it also includes organisms of different lifestyles (pathogens, mutualists, commensal, and free-living). genome content evolution of this group has not been studied in a systematic fashion, which would reveal genes underlying the emergence of pvc-specific phenotypes. here, we analyzed the evolutionary dynamics of 26 pvc genomes and several outgro ...201223221607
widespread occurrence of secondary lipid biosynthesis potential in microbial lineages.bacterial production of long-chain omega-3 polyunsaturated fatty acids (pufas), such as eicosapentaenoic acid (epa, 20:5n-3) and docosahexaenoic acid (dha, 22:6n-3), is constrained to a narrow subset of marine γ-proteobacteria. the genes responsible for de novo bacterial pufa biosynthesis, designated pfaeabcd, encode large, multi-domain protein complexes akin to type i iterative fatty acid and polyketide synthases, herein referred to as "pfa synthases". in addition to the archetypal pfa synthase ...201121629834
microbial cytochromes p450: biodiversity and biotechnology. where do cytochromes p450 come from, what do they do and what can they do for us?the first eukaryote genome revealed three yeast cytochromes p450 (cyps), hence the subsequent realization that some microbial fungal genomes encode these proteins in 1 per cent or more of all genes (greater than 100) has been surprising. they are unique biocatalysts undertaking a wide array of stereo- and regio-specific reactions and so hold promise in many applications. based on ancestral activities that included 14α-demethylation during sterol biosynthesis, it is now seen that cyps are part of ...201323297358
core from myxococcus xanthus is a copper-dependent rna polymerase sigma factor.the dual toxicity/essentiality of copper forces cells to maintain a tightly regulated homeostasis for this metal in all living organisms, from bacteria to humans. consequently, many genes have previously been reported to participate in copper detoxification in bacteria. myxococcus xanthus, a prokaryote, encodes many proteins involved in copper homeostasis that are differentially regulated by this metal. a σ factor of the ecf (extracytoplasmic function) family, core, has been found to regulate th ...201121655090
characterization of novel ompa-like protein of leptospira interrogans that binds extracellular matrix molecules and plasminogen.leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease of human and veterinary concern. the identification of novel proteins that mediate host-pathogen interactions is important for understanding the bacterial pathogenesis as well as to identify protective antigens that would help fight the disease. we describe in this work the cloning, expression, purification and characterization of three predicted leptospiral membrane proteins, lic10258, lic12880 (lp30) and lic12 ...201121755014
Gating NO Release from Nitric Oxide Synthase.We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV-vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for ...201122148177
phylogeny of rieske/cytb complexes with a special focus on the haloarchaeal enzymes.rieske/cytochrome b (rieske/cytb) complexes are proton pumping quinol oxidases that are present in most bacteria and archaea. the phylogeny of their subunits follows closely the 16s-rrna phylogeny, indicating that chemiosmotic coupling was already present in the last universal common ancestor of archaea and bacteria. haloarchaea are the only organisms found so far that acquired rieske/cytb complexes via interdomain lateral gene transfer. they encode two rieske/cytb complexes in their genomes; on ...201222798450
a new family of bacterial condensins.condensins play a central role in global chromatin organization. in bacteria, two families of condensins have been identified, the mukbef and smc-scpab complexes. only one of the two complexes is usually found in a given species, giving rise to a paradigm that a single condensin organizes bacterial chromosomes. using sequence analysis, we identified a third family of condensins, mksbef (mukbef-like smc proteins), which is broadly present in diverse bacteria. the proteins appear distantly related ...201121752107
evolution of the deaminase fold and multiple origins of eukaryotic editing and mutagenic nucleic acid deaminases from bacterial toxin systems.the deaminase-like fold includes, in addition to nucleic acid/nucleotide deaminases, several catalytic domains such as the jab domain, and others involved in nucleotide and adp-ribose metabolism. using sensitive sequence and structural comparison methods, we develop a comprehensive natural classification of the deaminase-like fold and show that its ancestral version was likely to operate on nucleotides or nucleic acids. consequently, we present evidence that a specific group of jab domains are l ...201121890906
phylogenetic analysis of six-domain multi-copper blue proteins.multicopper blue proteins, composed of several repetitive copper-binding domains similar to one-domain cupredoxin-like proteins, were found in almost all organisms. they are classified into the three different groups, based on their two-, three- or six-domain organization. we found orthologs of chordate six-domain copper-binding proteins in animals, plants, bacteria and archea. the phylogenetic analysis of 183 multicopper blue proteins and their copper-binding sites comparison make us think that ...201323516668
the eukaryotic translation initiation regulator cdc123 defines a divergent clade of atp-grasp enzymes with a predicted role in novel protein modifications.deciphering the origin of uniquely eukaryotic features of sub-cellular systems, such as the translation apparatus, is critical in reconstructing eukaryogenesis. one such feature is the highly conserved, but poorly understood, eukaryotic protein cdc123, which regulates the abundance of the eukaryotic translation initiation eif2 complex and binds one of its components eif2γ. we show that the eukaryotic protein cdc123 defines a novel clade of atp-grasp enzymes distinguished from all other members o ...201525976611
type i pyridoxal 5'-phosphate dependent enzymatic domains embedded within multimodular nonribosomal peptide synthetase and polyketide synthase assembly lines.pyridoxal 5'-phosphate (plp)-dependent enzymes of fold type i, the most studied structural class of the plp-dependent enzyme superfamily, are known to exist as stand-alone homodimers or homotetramers. these enzymes have been found also embedded in multimodular and multidomain assembly lines involved in the biosynthesis of polyketides (pks) and nonribosomal peptides (nrps). the aim of this work is to provide a proteome-wide view of the distribution and characteristics of type i domains covalently ...201324148833
genomics of bacteria and archaea: the emerging dynamic view of the prokaryotic world.the first bacterial genome was sequenced in 1995, and the first archaeal genome in 1996. soon after these breakthroughs, an exponential rate of genome sequencing was established, with a doubling time of approximately 20 months for bacteria and approximately 34 months for archaea. comparative analysis of the hundreds of sequenced bacterial and dozens of archaeal genomes leads to several generalizations on the principles of genome organization and evolution. a crucial finding that enables function ...200818948295
molecular evolution of urea amidolyase and urea carboxylase in fungi.urea amidolyase breaks down urea into ammonia and carbon dioxide in a two-step process, while another enzyme, urease, does this in a one step-process. urea amidolyase has been found only in some fungal species among eukaryotes. it contains two major domains: the amidase and urea carboxylase domains. a shorter form of urea amidolyase is known as urea carboxylase and has no amidase domain. eukaryotic urea carboxylase has been found only in several fungal species and green algae. in order to elucid ...201121447149
ge23077 binds to the rna polymerase 'i' and 'i+1' sites and prevents the binding of initiating nucleotides.using a combination of genetic, biochemical, and structural approaches, we show that the cyclic-peptide antibiotic ge23077 (ge) binds directly to the bacterial rna polymerase (rnap) active-center 'i' and 'i+1' nucleotide binding sites, preventing the binding of initiating nucleotides, and thereby preventing transcription initiation. the target-based resistance spectrum for ge is unusually small, reflecting the fact that the ge binding site on rnap includes residues of the rnap active center that ...201424755292
nitrate and periplasmic nitrate reductases.the nitrate anion is a simple, abundant and relatively stable species, yet plays a significant role in global cycling of nitrogen, global climate change, and human health. although it has been known for quite some time that nitrate is an important species environmentally, recent studies have identified potential medical applications. in this respect the nitrate anion remains an enigmatic species that promises to offer exciting science in years to come. many bacteria readily reduce nitrate to nit ...201424141308
distinguishing microbial genome fragments based on their composition: evolutionary and comparative genomic perspectives.it is well known that patterns of nucleotide composition vary within and among genomes, although the reasons why these variations exist are not completely understood. between-genome compositional variation has been exploited to assign environmental shotgun sequences to their most likely originating genomes, whereas within-genome variation has been used to identify recently acquired genetic material such as pathogenicity islands. recent sequence assignment techniques have achieved high levels of ...201020333228
a novel cold-adapted lipase from sorangium cellulosum strain so0157-2: gene cloning, expression, and enzymatic characterization.genome sequencing of cellulolytic myxobacterium sorangium cellulosum reveals many open-reading frames (orfs) encoding various degradation enzymes with low sequence similarity to those reported, but none of them has been characterized. in this paper, a predicted lipase gene (lipa) was cloned from s. cellulosum strain so0157-2 and characterized. lipa is 981-bp in size, encoding a polypeptide of 326 amino acids that contains the pentapeptide (ghsmg) and catalytic triad residues (ser114, asp250 and ...201122072918
the biofilm inhibitor carolacton disturbs membrane integrity and cell division of streptococcus mutans through the serine-threonine proteinkinase pknb.carolacton, a secondary metabolite isolated from the myxobacterium sorangium cellulosum, disturbs s. mutans biofilm viability at nanomolar concentrations. here we show that carolacton causes leakage of cytoplasmic content (dna and proteins) in growing cells at low ph and provide quantitative data on the membrane damage. furthermore we demonstrate that the biofilm specific activity of carolacton is due to the strong acidification occurring during biofilm growth. the chemical conversion of the ket ...201121840978
total synthesis of (-)-cp(2)-disorazole c(1).the total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole c(1) was accomplished in 23 steps and 1.1% overall yield. a vinyl cyclopropane cross-metathesis reaction generated a key (e)-alkene segment of the target molecule. ic(50) determinations of (-)-cp(2)-disorazole c(1) in human colon cancer cell lines indicated low nanomolar cytotoxic properties. accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not cont ...201121739942
structural and biochemical characterization of mycobacterium tuberculosis cyp142: evidence for multiple cholesterol 27-hydroxylase activities in a human pathogen.the mycobacterium tuberculosis cytochrome p450 enzyme cyp142 is encoded in a large gene cluster involved in metabolism of host cholesterol. cyp142 was expressed and purified as a soluble, low spin p450 hemoprotein. cyp142 binds tightly to cholesterol and its oxidized derivative cholest-4-en-3-one, with extensive shift of the heme iron to the high spin state. high affinity for azole antibiotics was demonstrated, highlighting their therapeutic potential. cyp142 catalyzes either 27-hydroxylation of ...201020889498
c6-c8 bridged epothilones: consequences of installing a conformational lock at the edge of the macrocycle.a series of conformationally restrained epothilone analogues with a short bridge between the methyl groups at c6 and c8 was designed to mimic the binding pose assigned to our recently reported epoa-microtubule binding model. a versatile synthetic route to these bridged epothilone analogues has been successfully devised and implemented. biological evaluation of the compounds against a2780 human ovarian cancer and pc3 prostate cancer cell lines suggested that the introduction of a bridge between c ...201122127984
bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases.abstract:201121816041
Non-contiguous finished genome sequence and contextual data of the filamentous soil bacterium Ktedonobacter racemifer type strain (SOSP1-21).Ktedonobacter racemifer corrig. Cavaletti et al. 2007 is the type species of the genus Ktedonobacter, which in turn is the type genus of the family Ktedonobacteraceae, the type family of the order Ktedonobacterales within the class Ktedonobacteria in the phylum 'Chloroflexi'. Although K. racemifer shares some morphological features with the actinobacteria, it is of special interest because it was the first cultivated representative of a deep branching unclassified lineage of otherwise uncultivat ...201122180814
identification of the treponema pallidum subsp. pallidum tp0092 (rpoe) regulon and its implications for pathogen persistence in the host and syphilis pathogenesis.bacteria often respond to harmful environmental stimuli with the induction of extracytoplasmic function (ecf) sigma (σ) factors that in turn direct rna polymerase to transcribe specific groups of response genes (or regulons) to minimize cellular damage and favor adaptation to the changed extracellular milieu. in treponema pallidum subsp. pallidum, the agent of syphilis, the tp0092 gene is predicted to code for the pathogen's only annotated ecf σ factor, homologous to rpoe, known in escherichia c ...201323243302
genome reduction promotes increase in protein functional complexity in bacteria.obligate pathogenic and endosymbiotic bacteria typically experience gene loss due to functional redundancy, asexuality, and genetic drift. we hypothesize that reduced genomes increase their functional complexity through protein multitasking, in which many genes adopt new roles to counteract gene loss. comparisons of interaction networks among six bacteria that have varied genome sizes (mycoplasma pneumoniae, treponema pallidum, helicobacter pylori, campylobacter jejuni, synechocystis sp., and my ...201323114380
vesiculation from pseudomonas aeruginosa under sos.bacterial infections can be aggravated by antibiotic treatment that induces sos response and vesiculation. this leads to a hypothesis concerning association of sos with vesiculation. to test it, we conducted multiple analyses of outer membrane vesicles (omvs) produced from the pseudomonas aeruginosa wild type in which sos is induced by ciprofloxacin and from the lexa noncleavable (lexan) strain in which sos is repressed. the levels of omv proteins, lipids, and cytotoxicity increased for both the ...201222448133
tandem assembly of the epothilone biosynthetic gene cluster by in vitro site-specific recombination.we describe a site-specific recombination-based tandem assembly (ssrta) method for reconstruction of biological parts in synthetic biology. the system was catalyzed by streptomyces phage φbt1 integrase, which belongs to the large serine recombinase subfamily. this one-step approach was efficient and accurate, and able to join multiple dna molecules in vitro in a defined order. thus, it could have applications in constructing metabolic pathways and genetic networks.201122355658
Biogeography and phylogenetic diversity of a cluster of exclusively marine myxobacteria.Myxobacteria are common in terrestrial habitats and well known for their formation of fruiting bodies and production of secondary metabolites. We studied a cluster of myxobacteria consisting only of sequences of marine origin (marine myxobacteria cluster, MMC) in sediments of the North Sea. Using a specific PCR, MMC sequences were detected in North Sea sediments down to 2.2?m depth, but not in the limnetic section of the Weser estuary and other freshwater habitats. In the water column, this clus ...201122189493
Biogeography and phylogenetic diversity of a cluster of exclusively marine myxobacteria.Myxobacteria are common in terrestrial habitats and well known for their formation of fruiting bodies and production of secondary metabolites. We studied a cluster of myxobacteria consisting only of sequences of marine origin (marine myxobacteria cluster, MMC) in sediments of the North Sea. Using a specific PCR, MMC sequences were detected in North Sea sediments down to 2.2?m depth, but not in the limnetic section of the Weser estuary and other freshwater habitats. In the water column, this clus ...201122189493
effects of site-directed mutagenesis of mgla on motility and swarming of myxococcus xanthus.the mgla gene from the bacterium myxococcus xanthus encodes a 22kda protein related to the ras superfamily of monomeric gtpases. mgla is required for the normal function of a-motility (adventurous), s-motility (social), fruiting body morphogenesis, and sporulation. mgla and its homologs differ from all eukaryotic and other prokaryotic gtpases because they have a threonine (thr78) in place of the highly conserved aspartate residue of the consensus pm3 (phosphate-magnesium binding) region. to iden ...201021083931
genome mining in streptomyces. elucidation of the role of baeyer-villiger monooxygenases and non-heme iron-dependent dehydrogenase/oxygenases in the final steps of the biosynthesis of pentalenolactone and neopentalenolactone.the pentalenolactone biosynthetic gene clusters have been cloned and sequenced from two known producers of the sesquiterpenoid antibiotic pentalenolactone, streptomyces exfoliatus uc5319 and streptomyces arenae tu¨469. the recombinant enzymes pene and pnte, from s. exfoliatus and s. arenae, respectively, catalyze the flavin-dependent baeyer-villiger oxidation of 1-deoxy-11-oxopentalenic acid (7) to pentalenolactone d (8). recombinant pend, pntd, and ptld, the latter from streptomyces avermitilis ...201121250661
p2cs: a two-component system resource for prokaryotic signal transduction research.with the escalation of high throughput prokaryotic genome sequencing, there is an ever-increasing need for databases that characterise, catalogue and present data relating to particular gene sets and genomes/metagenomes. two-component system (tcs) signal transduction pathways are the dominant mechanisms by which micro-organisms sense and respond to external as well as internal environmental changes. these systems respond to a wide range of stimuli by triggering diverse physiological adjustments, ...200919604365
insights into 4e-bp1 and p53 mediated regulation of accelerated cell senescence.senescence is a valid tumor suppressive mechanism in cancer. accelerated cell senescence describes the growth arrested state of cells that have been treated with anti-tumor drugs, such as doxorubicin that induce a dna damage response. discodermolide, a microtubule-stabilizing agent, is a potent inducer of accelerated cell senescence. resistance to discodermolide is mediated via resistance to accelerated cell senescence, and is associated with reduced expression of the mtorc1 substrate, 4e-bp1 an ...201121399233
phylogenetic co-occurrence of exor, exos, and chvi, components of the rsi bacterial invasion switch, suggests a key adaptive mechanism regulating the transition between free-living and host-invading phases in rhizobiales.both bacterial symbionts and pathogens rely on their host-sensing mechanisms to activate the biosynthetic pathways necessary for their invasion into host cells. the gram-negative bacterium sinorhizobium meliloti relies on its rsi (exor-exos-chvi) invasion switch to turn on the production of succinoglycan, an exopolysaccharide required for its host invasion. recent whole-genome sequencing efforts have uncovered putative components of rsi-like invasion switches in many other symbiotic and pathogen ...201526309130
across bacterial phyla, distantly-related genomes with similar genomic gc content have similar patterns of amino acid usage.the gc content of bacterial genomes ranges from 16% to 75% and wide ranges of genomic gc content are observed within many bacterial phyla, including both gram negative and gram positive phyla. thus, divergent genomic gc content has evolved repeatedly in widely separated bacterial taxa. since genomic gc content influences codon usage, we examined codon usage patterns and predicted protein amino acid content as a function of genomic gc content within eight different phyla or classes of bacteria. w ...201121423704
structure/function analysis of a type iii polyketide synthase in the brown alga ectocarpus siliculosus reveals a biochemical pathway in phlorotannin monomer biosynthesis.brown algal phlorotannins are structural analogs of condensed tannins in terrestrial plants and, like plant phenols, they have numerous biological functions. despite their importance in brown algae, phlorotannin biosynthetic pathways have been poorly characterized at the molecular level. we found that a predicted type iii polyketide synthase in the genome of the brown alga ectocarpus siliculosus, pks1, catalyzes a major step in the biosynthetic pathway of phlorotannins (i.e., the synthesis of ph ...201323983220
the unique hmuy gene sequence as a specific marker of porphyromonas gingivalis.porphyromonas gingivalis, a major etiological agent of chronic periodontitis, acquires heme from host hemoproteins using the hmuy hemophore. the aim of this study was to develop a specific p. gingivalis marker based on a hmuy gene sequence. subgingival samples were collected from 66 patients with chronic periodontitis and 40 healthy subjects and the entire hmuy gene was analyzed in positive samples. phylogenetic analyses demonstrated that both the amino acid sequence of the hmuy protein and the ...201323844074
polyketide genes in the marine sponge plakortis simplex: a new group of mono-modular type i polyketide synthases from sponge symbionts.sponge symbionts are a largely unexplored source of new and unusual metabolic pathways. insights into the distribution and function of metabolic genes of sponge symbionts are crucial to dissect and exploit their biotechnological potential. screening of the metagenome of the marine sponge plakortis simplex led to the discovery of the swf family, a new group of mono-modular type i polyketide synthase/fatty acid synthase (pks/fas) specifically associated with sponge symbionts. two different example ...201324249289
chemosensory regulation of a heat-repeat protein couples aggregation and sporulation in myxococcus xanthus.chemosensory systems are complex, highly modified two-component systems (tcs) used by bacteria to control various biological functions ranging from motility to sporulation. chemosensory systems and tcs both modulate phosphorelays comprised of histidine kinases and response regulators, some of which are single-domain response regulators (sd-rrs) such as chey. in this study, we have identified and characterized the che7 chemosensory system of myxococcus xanthus, a common soil bacterium which displ ...201424957622
tir domain-containing adaptor sarm is a late addition to the ongoing microbe-host dialog.toll/interleukin-1 receptor (tir) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein-protein interactions. among them is sarm, the only tir domain-containing adaptor that can negatively regulate tlr signaling. by extensive phylogenetic analysis, we show here that sarm is closely related to bacterial proteins with tir domains, suggesting that this family has a different ...201021110998
tir domain-containing adaptor sarm is a late addition to the ongoing microbe-host dialog.toll/interleukin-1 receptor (tir) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein-protein interactions. among them is sarm, the only tir domain-containing adaptor that can negatively regulate tlr signaling. by extensive phylogenetic analysis, we show here that sarm is closely related to bacterial proteins with tir domains, suggesting that this family has a different ...201021110998
xenobiotic efflux in bacteria and fungi: a genomics update. 201121692371
bacterial sigma factors and anti-sigma factors: structure, function and distribution.sigma factors are multi-domain subunits of bacterial rna polymerase (rnap) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in rna synthesis. this review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (groups 2-4) that control a w ...201526131973
planctomycetes as novel source of bioactive molecules.marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. of particular importance are organisms like sponges and macroalgae and their associated microbiome. planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the actinobacteria. furthermore, genome mining revealed t ...201627570520
in silico characterization of pectate lyase protein sequences from different source organisms.a total of 121 protein sequences of pectate lyases were subjected to homology search, multiple sequence alignment, phylogenetic tree construction, and motif analysis. the phylogenetic tree constructed revealed different clusters based on different source organisms representing bacterial, fungal, plant, and nematode pectate lyases. the multiple accessions of bacterial, fungal, nematode, and plant pectate lyase protein sequences were placed closely revealing a sequence level similarity. the multip ...201021048874
structural, functional, and genetic analysis of sorangicin inhibition of bacterial rna polymerase.a combined structural, functional, and genetic approach was used to investigate inhibition of bacterial rna polymerase (rnap) by sorangicin (sor), a macrolide polyether antibiotic. sor lacks chemical and structural similarity to the ansamycin rifampicin (rif), an rnap inhibitor widely used to treat tuberculosis. nevertheless, structural analysis revealed sor binds in the same rnap beta subunit pocket as rif, with almost complete overlap of rnap binding determinants, and functional analysis revea ...200515692574
identification and characterization of novel cellulolytic and hemicellulolytic genes and enzymes derived from german grassland soil metagenomes.soil metagenomes represent an unlimited resource for the discovery of novel biocatalysts from soil microorganisms. three large-inserts metagenomic dna libraries were constructed from different grassland soil samples and screened for genes conferring cellulase or xylanase activity. function-driven screening identified a novel cellulase-encoding gene (cel01) and two xylanase-encoding genes (xyn01 and xyn02). from sequence and protein domain analyses, cel01 (831 amino acids) belongs to glycoside hy ...201222187078
identification and characterization of novel cellulolytic and hemicellulolytic genes and enzymes derived from german grassland soil metagenomes.soil metagenomes represent an unlimited resource for the discovery of novel biocatalysts from soil microorganisms. three large-inserts metagenomic dna libraries were constructed from different grassland soil samples and screened for genes conferring cellulase or xylanase activity. function-driven screening identified a novel cellulase-encoding gene (cel01) and two xylanase-encoding genes (xyn01 and xyn02). from sequence and protein domain analyses, cel01 (831 amino acids) belongs to glycoside hy ...201222187078
antibiotics trapping transcription initiation intermediates: to melt or to bend, what's first?promoter dna melting, culminating in the loading of the single-stranded dna template into the rna polymerase active site, is a key step in transcription initiation. recently, the first transcription inhibitors found to block distinct steps of promoter melting were characterized. here, the impact of these studies is discussed with respect to the current models of transcription initiation.201121468230
phase i dose escalation study of kos-1584, a novel epothilone, in patients with advanced solid tumors.first-in-man study of kos-1584, a second generation epothilone.201121874318
phase i dose escalation study of kos-1584, a novel epothilone, in patients with advanced solid tumors.first-in-man study of kos-1584, a second generation epothilone.201121874318
inter-phylum hgt has shaped the metabolism of many mesophilic and anaerobic bacteria.genome sequencing has revealed that horizontal gene transfer (hgt) is a major evolutionary process in bacteria. although it is generally assumed that closely related organisms engage in genetic exchange more frequently than distantly related ones, the frequency of hgt among distantly related organisms and the effect of ecological relatedness on the frequency has not been rigorously assessed. here, we devised a novel bioinformatic pipeline, which minimized the effect of over-representation of spe ...201425314320
cell contact-dependent outer membrane exchange in myxobacteria: genetic determinants and mechanism.biofilms are dense microbial communities. although widely distributed and medically important, how biofilm cells interact with one another is poorly understood. recently, we described a novel process whereby myxobacterial biofilm cells exchange their outer membrane (om) lipoproteins. for the first time we report here the identification of two host proteins, traab, required for transfer. these proteins are predicted to localize in the cell envelope; and traa encodes a distant pa14 lectin-like dom ...201222511878
inter-phylum hgt has shaped the metabolism of many mesophilic and anaerobic bacteria.genome sequencing has revealed that horizontal gene transfer (hgt) is a major evolutionary process in bacteria. although it is generally assumed that closely related organisms engage in genetic exchange more frequently than distantly related ones, the frequency of hgt among distantly related organisms and the effect of ecological relatedness on the frequency has not been rigorously assessed. here, we devised a novel bioinformatic pipeline, which minimized the effect of over-representation of spe ...201425314320
extraordinary expansion of a sorangium cellulosum genome from an alkaline milieu.complex environmental conditions can significantly affect bacterial genome size by unknown mechanisms. the so0157-2 strain of sorangium cellulosum is an alkaline-adaptive epothilone producer that grows across a wide ph range. here, we show that the genome of this strain is 14,782,125 base pairs, 1.75-megabases larger than the largest bacterial genome from s. cellulosum reported previously. the total 11,599 coding sequences (cdss) include massive duplications and horizontally transferred genes, r ...201323812535
draft genome of a type 4 pilus defective myxococcus xanthus strain, dzf1.myxococcus xanthus is a member of the myxococcales order within the deltaproteobacterial subdivision. here, we report the whole-genome shotgun sequence of the type iv pilus (t4p) defective strain dzf1, which includes many genes found in strain dz2 but absent from strain dk1622.201323788552
draft genome sequence of myxococcus xanthus wild-type strain dz2, a model organism for predation and development.myxococcus xanthus is a member of the myxococcales order within the deltaproteobacteria subdivision. the myxobacteria reside in soil, have relatively large genomes, and display complex life cycles. here, we report the whole-genome shotgun sequence of strain dz2, which includes unique genes not found previously in strain dk1622.201323661486
a modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme.angiotensin-converting enzyme (ace) is a zinc-dependent peptidase responsible for converting angiotensin i into the vasoconstrictor angiotensin ii. however, ace is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. because of this, ace and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. the defining feature of ac ...201323257181
approach to analyze the diversity of myxobacteria in soil by semi-nested pcr-denaturing gradient gel electrophoresis (dgge) based on taxon-specific gene.the genotypic diversity of insoluble macromolecules degraded myxobacteria, provided an opportunity to discover new bacterial resources and find new ecological functions. in this study, we developed a semi-nested-pcr-denaturing gradient gel electrophoresis (dgge) strategy to determine the presence and genotypic diversity of myxobacteria in soil. after two rounds of pcr with myxobacteria-specific primers, an 194 bp fragment of mgla, a key gene involved in gliding motility, suitable for dgge was ob ...201425280065
multisubstrate isotope labeling and metagenomic analysis of active soil bacterial communities.soil microbial diversity represents the largest global reservoir of novel microorganisms and enzymes. in this study, we coupled functional metagenomics and dna stable-isotope probing (dna-sip) using multiple plant-derived carbon substrates and diverse soils to characterize active soil bacterial communities and their glycoside hydrolase genes, which have value for industrial applications. we incubated samples from three disparate canadian soils (tundra, temperate rainforest, and agricultural) wit ...201425028422
polymorphic toxin systems: comprehensive characterization of trafficking modes, processing, mechanisms of action, immunity and ecology using comparative genomics.proteinaceous toxins are observed across all levels of inter-organismal and intra-genomic conflicts. these include recently discovered prokaryotic polymorphic toxin systems implicated in intra-specific conflicts. they are characterized by a remarkable diversity of c-terminal toxin domains generated by recombination with standalone toxin-coding cassettes. prior analysis revealed a striking diversity of nuclease and deaminase domains among the toxin modules. we systematically investigated polymorp ...201222731697
diversity of epothilone producers among sorangium strains in producer-positive soil habitats.large-scale surveys show that the anti-tumour compounds known as epothilones are produced by only a small proportion of sorangium strains, thereby greatly hampering the research and development of these valuable compounds. in this study, to investigate the niche diversity of epothilone-producing sorangium strains, we re-surveyed four soil samples where epothilone producers were previously found. compared with the < 2.5% positive strains collected from different places, epothilone producers compr ...201424308800
diversity of epothilone producers among sorangium strains in producer-positive soil habitats.large-scale surveys show that the anti-tumour compounds known as epothilones are produced by only a small proportion of sorangium strains, thereby greatly hampering the research and development of these valuable compounds. in this study, to investigate the niche diversity of epothilone-producing sorangium strains, we re-surveyed four soil samples where epothilone producers were previously found. compared with the < 2.5% positive strains collected from different places, epothilone producers compr ...201424308800
maxbin: an automated binning method to recover individual genomes from metagenomes using an expectation-maximization algorithm.recovering individual genomes from metagenomic datasets allows access to uncultivated microbial populations that may have important roles in natural and engineered ecosystems. understanding the roles of these uncultivated populations has broad application in ecology, evolution, biotechnology and medicine. accurate binning of assembled metagenomic sequences is an essential step in recovering the genomes and understanding microbial functions.201425136443
highly active and specific tyrosine ammonia-lyases from diverse origins enable enhanced production of aromatic compounds in bacteria and saccharomyces cerevisiae.phenylalanine and tyrosine ammonia-lyases form cinnamic acid and p-coumaric acid, which are precursors of a wide range of aromatic compounds of biotechnological interest. lack of highly active and specific tyrosine ammonia-lyases has previously been a limitation in metabolic engineering approaches. we therefore identified 22 sequences in silico using synteny information and aiming for sequence divergence. we performed a comparative in vivo study, expressing the genes intracellularly in bacteria ...201525911487
veillonella, firmicutes: microbes disguised as gram negatives.the firmicutes represent a major component of the intestinal microflora. the intestinal firmicutes are a large, diverse group of organisms, many of which are poorly characterized due to their anaerobic growth requirements. although most firmicutes are gram positive, members of the class negativicutes, including the genus veillonella, stain gram negative. veillonella are among the most abundant organisms of the oral and intestinal microflora of animals and humans, in spite of being strict anaerob ...201324976898
abundance and distribution of the highly iterated palindrome 1 (hip1) among prokaryotes.we have studied the abundance and phylogenetic distribution of the highly iterated palindrome 1 (hip1) among sequenced prokaryotic genomes. we show that an overrepresentation of hip1 is exclusive of some lineages of cyanobacteria, and that this abundance was gained only once during evolution and was subsequently lost in the lineage leading to marine pico-cyanobacteria. we show that among cyanobacterial protein sequences with annotated pfam domains, only opca (glucose 6-phosphate dehydrogenase as ...201122312590
update on refseq microbial genomes resources.ncbi refseq genome collection http://www.ncbi.nlm.nih.gov/genome represents all three major domains of life: eukarya, bacteria and archaea as well as viruses. prokaryotic genome sequences are the most rapidly growing part of the collection. during the year of 2014 more than 10,000 microbial genome assemblies have been publicly released bringing the total number of prokaryotic genomes close to 30,000. we continue to improve the quality and usability of the microbial genome resources by providing ...201425510495
prokaryote-derived protein inhibitors of peptidases: a sketchy occurrence and mostly unknown function.in metazoan organisms protein inhibitors of peptidases are important factors essential for regulation of proteolytic activity. in vertebrates genes encoding peptidase inhibitors constitute up to 1% of genes reflecting a need for tight and specific control of proteolysis especially in extracellular body fluids. in stark contrast unicellular organisms, both prokaryotic and eukaryotic consistently contain only few, if any, genes coding for putative peptidase inhibitors. this may seem perplexing in ...201020558234
antibiotics from predatory bacteria.bacteria, which prey on other microorganisms, are commonly found in the environment. while some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. here, we will present ...201627340451
bacterial transcription as a target for antibacterial drug development.transcription, the first step of gene expression, is carried out by the enzyme rna polymerase (rnap) and is regulated through interaction with a series of protein transcription factors. rnap and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. the determination ...201626764017
the complete genome sequence and analysis of a plasmid-bearing myxobacterial strain myxococcus fulvus 124b02 (m 206081).myxobacteria, phylogenetically located in the delta division of the proteobacteria, are well known for characterized social behaviors and large genomes of more than 9 mb in size. myxococcus fulvus is a typical species of the genus myxococcus in the family myxococcaceae. m. fulvus 124b02, originally isolated from a soil sample collected in northeast china, is the one and only presently known myxobacterial strain that harbors an endogenous autonomously replicating plasmid, named pmf1. the endogeno ...201626734118
comparison of myxobacterial diversity and evaluation of isolation success in two niches: kiritimati island and german compost.myxobacteria harbor an enormous potential for new bioactive secondary metabolites and therefore the isolation of in particular new groups is of great interest. the diversity of myxobacteria present in two ecological habitats, namely sand from kiritimati island and german compost, was evaluated by both cultivation-based and cultivation-independent methods. phylogenetic analyses of the strains in comparison with 16s rrna gene sequences from cultured and uncultured material in genbank revealed a gr ...201626669488
comparison of myxobacterial diversity and evaluation of isolation success in two niches: kiritimati island and german compost.myxobacteria harbor an enormous potential for new bioactive secondary metabolites and therefore the isolation of in particular new groups is of great interest. the diversity of myxobacteria present in two ecological habitats, namely sand from kiritimati island and german compost, was evaluated by both cultivation-based and cultivation-independent methods. phylogenetic analyses of the strains in comparison with 16s rrna gene sequences from cultured and uncultured material in genbank revealed a gr ...201626669488
possibility of bacterial recruitment of plant genes associated with the biosynthesis of secondary metabolites. 200312857798
in silico analysis of methyltransferase domains involved in biosynthesis of secondary metabolites.secondary metabolites biosynthesized by polyketide synthase (pks) and nonribosomal peptide synthetase (nrps) family of enzymes constitute several classes of therapeutically important natural products like erythromycin, rapamycin, cyclosporine etc. in view of their relevance for natural product based drug discovery, identification of novel secondary metabolite natural products by genome mining has been an area of active research. a number of different tailoring enzymes catalyze a variety of chemi ...200818950525
pcr detection of type i polyketide synthase genes in myxobacteria.the diversity of type i modular polyketide synthase (pks) was explored by pcr amplification of dna encoding ketosynthase and acyltransferase domains in myxobacteria. the sequencing of the amplicons revealed that many pks genes were distantly related to the published sequences. thus, myxobacteria may be excellent resources for novel and diverse polyketides.200818606793
type i polyketide synthases that require discrete acyltransferases.the diverse structures of polyketide natural products are reflected by the equally diverse polyketide biosynthetic enzymes, namely polyketide synthases (pkss). three major classes of pkss are known-noniterative type i pkss, iterative type ii pkss and acyl carrier protein-independent type iii pkss, each of which consists of additional variants. one such variant is the noniterative type i pks in which each pks module lacks the cognate acyltransferase (at) domain. the essential at activity is inste ...200919362640
networks of gene sharing among 329 proteobacterial genomes reveal differences in lateral gene transfer frequency at different phylogenetic depths.lateral gene transfer (lgt) is an important mechanism of natural variation among prokaryotes. over the full course of evolution, most or all of the genes resident in a given prokaryotic genome have been affected by lgt, yet the frequency of lgt can vary greatly across genes and across prokaryotic groups. the proteobacteria are among the most diverse of prokaryotic taxa. the prevalence of lgt in their genome evolution calls for the application of network-based methods instead of tree-based method ...201021059789
networks of gene sharing among 329 proteobacterial genomes reveal differences in lateral gene transfer frequency at different phylogenetic depths.lateral gene transfer (lgt) is an important mechanism of natural variation among prokaryotes. over the full course of evolution, most or all of the genes resident in a given prokaryotic genome have been affected by lgt, yet the frequency of lgt can vary greatly across genes and across prokaryotic groups. the proteobacteria are among the most diverse of prokaryotic taxa. the prevalence of lgt in their genome evolution calls for the application of network-based methods instead of tree-based method ...201021059789
molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases.cytosolic glutathione transferases (cgst) are a large group of ubiquitous enzymes involved in detoxification and are well known for their undesired side effects during chemotherapy. in this work we have performed thorough phylogenetic analyses to understand the various aspects of the evolution and functional diversification of cgsts. furthermore, we assessed plausible correlations between gene duplication and substrate specificity of gene paralogs in humans and selected species, notably in mamma ...201020843339
update on refseq microbial genomes resources.ncbi refseq genome collection http://www.ncbi.nlm.nih.gov/genome represents all three major domains of life: eukarya, bacteria and archaea as well as viruses. prokaryotic genome sequences are the most rapidly growing part of the collection. during the year of 2014 more than 10,000 microbial genome assemblies have been publicly released bringing the total number of prokaryotic genomes close to 30,000. we continue to improve the quality and usability of the microbial genome resources by providing ...201425510495
a brief review: the z-curve theory and its application in genome analysis.in theoretical physics, there exist two basic mathematical approaches, algebraic and geometrical methods, which, in most cases, are complementary. in the area of genome sequence analysis, however, algebraic approaches have been widely used, while geometrical approaches have been less explored for a long time. the z-curve theory is a geometrical approach to genome analysis. the z-curve is a three-dimensional curve that represents a given dna sequence in the sense that each can be uniquely reconst ...201424822026
effect of antimicrobial growth promoter administration on the intestinal microbiota of beef cattle.antimicrobial growth promoters (agps) are antimicrobial agents administered to livestock in feed for prolonged periods to enhance feed efficiency. beef cattle are primarily finished in confined feeding operations in canada and the usa, and the administration of agps such as chlortetracycline and sulfamethazine (aureo s-700 g) is the standard. the impacts of agps on the intestinal microbiota of beef cattle are currently uncertain; it is documented that agps administered to beef cattle pass throug ...201323578222
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