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discovering new bioactive molecules from microbial sources.there is an increased need for new drug leads to treat diseases in humans, animals and plants. a dramatic example is represented by the need for novel and more effective antibiotics to combat multidrug-resistant microbial pathogens. natural products represent a major source of approved drugs and still play an important role in supplying chemical diversity, despite a decreased interest by large pharmaceutical companies. novel approaches must be implemented to decrease the chances of rediscovering ...201424661414
evaluating nonpolar surface area and liquid chromatography/mass spectrometry response: an application for site occupancy measurements for enzyme intermediates in polyketide biosynthesis.site occupancy measurements using liquid chromatography/mass spectrometry (lc/ms) are reported throughout the literature. however, site occupancy quantification suffers from ionization bias between modified and unmodified peptides containing the active site. in this study, we explore the ms signal as a function of nonpolar surface area (npsa) in order to better understand this bias in electrospray response. the correlation between hydrophobicity and lc/ms response was evaluated and applied to st ...201425366398
nucleo-cytoplasmic transport as a therapeutic target of cancer.shuttling of specific proteins out of the nucleus is essential for the regulation of the cell cycle and proliferation of both normal and malignant tissues. dysregulation of this fundamental process may affect many other important cellular processes such as tumor growth, inflammatory response, cell cycle, and apoptosis. it is known that xpo1 (exportin-1/chromosome region maintenance 1/crm1) is the main mediator of nuclear export in many cell types. nuclear proteins exported to the cytoplasm by xp ...201425476752
cellulolytic potential under environmental changes in microbial communities from grassland litter.in many ecosystems, global changes are likely to profoundly affect microorganisms. in southern california, changes in precipitation and nitrogen deposition may influence the composition and functional potential of microbial communities and their resulting ability to degrade plant material. to test whether such environmental changes impact the distribution of functional groups involved in leaf litter degradation, we determined how the genomic diversity of microbial communities in a semi-arid gras ...201425505459
antimalarial activity of the myxobacterial macrolide chlorotonil a.myxobacteria are gram-negative soil-dwelling bacteria belonging to the phylum proteobacteria. they are a rich source of promising compounds for clinical application, such as epothilones for cancer therapy and several new antibiotics. in the course of a bioactivity screening program of secondary metabolites produced by sorangium cellulosum strains, the macrolide chlorotonil a was found to exhibit promising antimalarial activity. subsequently, we evaluated chlorotonil a against plasmodium falcipar ...201425114138
a conserved proline triplet in val-trna synthetase and the origin of elongation factor p.bacterial ribosomes stall on polyproline stretches and require the elongation factor p (ef-p) to relieve the arrest. yet it remains unclear why evolution has favored the development of ef-p rather than selecting against the occurrence of polyproline stretches in proteins. we have discovered that only a single polyproline stretch is invariant across all domains of life, namely a proline triplet in vals, the trna synthetase, that charges trna(val) with valine. here, we show that expression of vals ...201425310979
a group of sequence-related sphingomonad enzymes catalyzes cleavage of β-aryl ether linkages in lignin β-guaiacyl and β-syringyl ether dimers.lignin biosynthesis occurs via radical coupling of guaiacyl and syringyl hydroxycinnamyl alcohol monomers (i.e., "monolignols") through chemical condensation with the growing lignin polymer. with each chain-extension step, monolignols invariably couple at their β-positions, generating chiral centers. here, we report on activities of bacterial glutathione-s-transferase (gst) enzymes that cleave β-aryl ether bonds in lignin dimers that are composed of different monomeric units. our data reveal tha ...201425232892
nitric oxide production by necrotrophic pathogen macrophomina phaseolina and the host plant in charcoal rot disease of jute: complexity of the interplay between necrotroph-host plant interactions.m. phaseolina, a global devastating necrotrophic fungal pathogen causes charcoal rot disease in more than 500 host plants. with the aim of understanding the plant-necrotrophic pathogen interaction associated with charcoal rot disease of jute, biochemical approach was attempted to study cellular nitric oxide production under diseased condition. this is the first report on m. phaseolina infection in corchorus capsularis (jute) plants which resulted in elevated nitric oxide, reactive nitrogen speci ...201425208092
metagenome fragment classification based on multiple motif-occurrence profiles.a vast amount of metagenomic data has been obtained by extracting multiple genomes simultaneously from microbial communities, including genomes from uncultivable microbes. by analyzing these metagenomic data, novel microbes are discovered and new microbial functions are elucidated. the first step in analyzing these data is sequenced-read classification into reference genomes from which each read can be derived. the naïve bayes classifier is a method for this classification. to identify the deriv ...201425210663
synthesis and evaluation of novel analogues of ripostatins.ripostatins are polyene macrolactones isolated from the myxobacterium sorangium cellulosum. they exhibit antibiotic activity by inhibiting bacterial rna polymerase (rnap) through a binding site and mechanism that are different from those of current antibacterial drugs. thus, the ripostatins serve as starting points for the development of new anti-infective agents with a novel mode of action. in this work, several derivatives of ripostatins were produced. 15-desoxyripostatin a was synthesized by ...201425112727
assessing the effects of adsorptive polymeric resin additions on fungal secondary metabolite chemical diversity.adsorptive polymeric resins have been occasionally described to enhance the production of specific secondary metabolites (sms) of interest. methods that induce the expression of new chemical entities in fungal fermentations may lead to the discovery of new bioactive molecules and should be addressed as possible tools for the creation of new microbial chemical libraries for drug lead discovery. herein, we apply both biological activity and chemical evaluations to assess the use of adsorptive resi ...201425379340
two drugs are better than one. a short history of combined therapy of ovarian cancer.combined therapy of ovarian cancer has a long history. it has been applied for many years. the first drug which was commonly combined with other chemotherapeutics was cisplatin. it turned out to be effective given together with alkylating agents as well as with taxanes. another drug which is often the basis of first-line therapy is doxorubicin. the use of traditional chemotherapy is often limited due to side effects. this is why new drugs, targeted specifically at cancer cells (e.g. monoclonal a ...201426793017
two drugs are better than one. a short history of combined therapy of ovarian cancer.combined therapy of ovarian cancer has a long history. it has been applied for many years. the first drug which was commonly combined with other chemotherapeutics was cisplatin. it turned out to be effective given together with alkylating agents as well as with taxanes. another drug which is often the basis of first-line therapy is doxorubicin. the use of traditional chemotherapy is often limited due to side effects. this is why new drugs, targeted specifically at cancer cells (e.g. monoclonal a ...201426793017
randal: a randomized approach to aligning dna sequences to reference genomes.the alignment of short reads generated by next-generation sequencers to genomes is an important problem in many biomedical and bioinformatics applications. although many proposed methods work very well on narrow ranges of read lengths, they tend to suffer in performance and alignment quality for reads outside of these ranges.201425081493
expansion of the aminoglycoside-resistance 16s rrna (m(1)a1408) methyltransferase family: expression and functional characterization of four hypothetical enzymes of diverse bacterial origin.the global dissemination, potential activity in diverse species and broad resistance spectrum conferred by the aminoglycoside-resistance ribosomal rna methyltransferases make them a significant potential new threat to the efficacy of aminoglycoside antibiotics in the treatment of serious bacterial infections. the n1 methylation of adenosine 1408 (m(1)a1408) confers resistance to structurally diverse aminoglycosides, including kanamycin, neomycin and apramycin. the limited analyses to date of the ...201424963996
chemical inhibition of acetyl-coa carboxylase suppresses self-renewal growth of cancer stem cells.cancer stem cells (csc) may take advantage of the warburg effect-induced siphoning of metabolic intermediates into de novo fatty acid biosynthesis to increase self-renewal growth. we examined the anti-csc effects of the antifungal polyketide soraphen a, a specific inhibitor of the first committed step of lipid biosynthesis catalyzed by acetyl-coa carboxylase (acaca). the mammosphere formation capability of mcf-7 cells was reduced following treatment with soraphen a in a dose-dependent manner. mc ...201425246709
construction and verification of the transcriptional regulatory response network of streptococcus mutans upon treatment with the biofilm inhibitor carolacton.carolacton is a newly identified secondary metabolite causing altered cell morphology and death of streptococcus mutans biofilm cells. to unravel key regulators mediating these effects, the transcriptional regulatory response network of s. mutans biofilms upon carolacton treatment was constructed and analyzed. a systems biological approach integrating time-resolved transcriptomic data, reverse engineering, transcription factor binding sites, and experimental validation was carried out.201424884510
antiproliferative and hepatoprotective activity of metabolites from corynebacterium xerosis against ehrlich ascites carcinoma cells.to find out the effective anticancer drugs from bacterial products, petroleum ether extract of corynebacterium xerosis.201425183099
microtubule-targeting agents in oncology and therapeutic potential in hepatocellular carcinoma.in mammalian cells, microtubules are present both in interphase and dividing cells. in the latter, microtubules forming the mitotic spindle are highly dynamic and exquisitely sensitive to therapeutic inhibitors. developed to alter microtubule function, microtubule-binding agents have been proven to be highly active as an anticancer treatment. significant development of microtubule-binding agents has taken place in recent years, with newer anti-tubulin agents now showing novel properties of enhan ...201424790457
multiple effects of a novel epothilone analog on cellular processes and signaling pathways regulated by rac1 gtpase in the human breast cancer cells.the epothilones are a class of microtubule inhibitors that exhibit a strong antitumor activity. utd2 is a novel epothilone analog generated by genetic manipulation of the polyketide biosynthetic gene cluster. this study investigated the effects of utd2 on the actin cytoskeleton and its critical regulators, and the signaling pathways which are essential for cell motility, growth and survival in mcf-7 breast cancer cells. results showed that utd2 inhibited the cellular functions of actin cytoskele ...201424757372
recent advances in the identification of replication origins based on the z-curve method.precise dna replication is critical for the maintenance of genetic integrity in all organisms. in all three domains of life, dna replication starts at a specialized locus, termed as the replication origin, oric or ori, and its identification is vital to understanding the complex replication process. in bacteria and eukaryotes, replication initiates from single and multiple origins, respectively, while archaea can adopt either of the two modes. the z-curve method has been successfully used to ide ...201424822028
enzymatic synthesis of epothilone a glycosides.epothilones are extremely cytotoxic chemotherapeutic agents with epoxide, thiazole, and ketone groups that share equipotent kinetic similarity with taxol. the in vitro glycosylation catalyzed by uridine diphosphate glucosyltransferase (yjic) from bacillus licheniformis generated six novel epothilone a glycoside analouges including epothilone a 7-o-β-d-glucoside, epothilone a 7-o-β-d-galactoside, epothilone a 3,7-o-β-d-digalactoside, epothilone a 7-o-β-d-2-deoxyglucoside, epothilone a 7-o-β-l-rha ...201424949266
strong genome-wide selection early in the evolution of prochlorococcus resulted in a reduced genome through the loss of a large number of small effect genes.the smallest genomes of any photosynthetic organisms are found in a group of free-living marine cyanobacteria, prochlorococcus. to determine the underlying evolutionary mechanisms, we developed a new method to reconstruct the steps leading to the prochlorococcus genome reduction using 12 prochlorococcus and 6 marine synechococcus genomes. our results reveal that small genome sizes within prochlorococcus were largely determined shortly after the split of prochlorococcus and synechococcus (an earl ...201424594762
evolutionary insights about bacterial glxrs from whole genome analyses: is glurs2 a chimera?evolutionary histories of glutamyl-trna synthetase (glurs) and glutaminyl-trna synthetase (glnrs) in bacteria are convoluted. after the divergence of eubacteria and eukarya, bacterial glurs glutamylated both trnagln and trnaglu until glnrs appeared by horizontal gene transfer (hgt) from eukaryotes or a duplicate copy of glurs (glurs2) that only glutamylates trnagln appeared. the current understanding is based on limited sequence data and not always compatible with available experimental results. ...201424521160
identification and characterization of the biosynthetic gene cluster of polyoxypeptin a, a potent apoptosis inducer.polyoxypeptin a was isolated from a culture broth of streptomyces sp. mk498-98 f14, which has a potent apoptosis-inducing activity towards human pancreatic carcinoma aspc-1 cells. structurally, polyoxypeptin a is composed of a c₁₅ acyl side chain and a nineteen-membered cyclodepsipeptide core that consists of six unusual nonproteinogenic amino acid residues (n-hydroxyvaline, 3-hydroxy-3-methylproline, 5-hydroxypiperazic acid, n-hydroxyalanine, piperazic acid, and 3-hydroxyleucine) at high oxidat ...201424506891
the myxobacterial metabolite ratjadone a inhibits hiv infection by blocking the rev/crm1-mediated nuclear export pathway.the nuclear export of unspliced and partially spliced hiv-1 mrna is mediated by the recognition of a leucine-rich nuclear export signal (nes) in the hiv rev protein by the host protein crm1/exportin1. this makes the crm1-rev complex an attractive target for the development of new antiviral drugs. here we tested the anti-hiv efficacy of ratjadone a, a crm1 inhibitor derived from myxobacteria.201424475978
epothilones: from discovery to clinical trials.epothilones are natural compounds isolated from a myxobacterium at the beginning of the 1990s, and showed a remarkable anti-neoplastic activity. they act through the same mechanism of action of paclitaxel, by stabilizing microtubules and inducing apoptosis. although, their chemical structure, simpler than taxanes, makes them more suitable for derivatization. their interesting pharmacokinetic and bioavailabilty profiles, and the activity against paclitaxel-resistant cell lines make them interesti ...201425434353
identification of a novel antibiotic from myxobacterium stigmatella eracta wxnxj-b and evaluation of its antitumor effects i n - vitro.this work was to isolate and identify the bioactive secondary metabolite which was produced by myxobacterium stigmatella eracta wxnxj-b, and to evaluate its antitumor and apoptosis-inducing effects. the results showed that one novel compound (molecular formula c29h25no3) was isolated, purified by sephadex lh-20 column chromatography and preparative rp-hplc, and identified as 5-(6-benzyl-quinolin-3-ylmethyl)-6- phenyl-3,7-dioxa- bicycle [4.1.0] heptan-3-one (named as quinoxalone) according to its ...201424734069
identification of a cyclosporine-specific p450 hydroxylase gene through targeted cytochrome p450 complement (cypome) disruption in sebekia benihana.it was previously proposed that regio-specific hydroxylation of an immunosuppressive cyclosporine (csa) at the 4th n-methyl leucine is mediated by cytochrome p450 hydroxylase (cyp) in the rare actinomycete sebekia benihana. this modification is thought to be the reason for the hair growth-promoting side effect without the immunosuppressive activity of csa. through s. benihana genome sequencing and in silico analysis, we identified the complete cytochrome p450 complement (cypome) of s. benihana, ...201323354713
synthesis of isotopically labeled epothilones.the epothilones, including epothilones b and d, are macrocyclic lactones, which have potent cytotoxicities and promote the polymerization of tubulin to mictotubules by binding to and stabilizing the tubulin polymer. they have a very similar mechanism of action to paclitaxel (taxol®). the determination of the microtubule-binding conformation of the epothilones is an important piece of information in designing improved analogs for possible clinical use, and internuclear distance information that w ...201324307484
synthesis of isotopically labeled epothilones.the epothilones, including epothilones b and d, are macrocyclic lactones, which have potent cytotoxicities and promote the polymerization of tubulin to mictotubules by binding to and stabilizing the tubulin polymer. they have a very similar mechanism of action to paclitaxel (taxol®). the determination of the microtubule-binding conformation of the epothilones is an important piece of information in designing improved analogs for possible clinical use, and internuclear distance information that w ...201324307484
computational identification and analysis of orphan assembly-line polyketide synthases.the increasing availability of dna sequence data offers an opportunity for identifying new assembly-line polyketide synthases (pkss) that produce biologically active natural products. we developed an automated method to extract and consolidate all multimodular pks sequences (including hybrid pks/non-ribosomal peptide synthetases) in the national center for biotechnology information (ncbi) database, generating a non-redundant catalog of 885 distinct assembly-line pkss, the majority of which were ...201324301183
computational identification and analysis of orphan assembly-line polyketide synthases.the increasing availability of dna sequence data offers an opportunity for identifying new assembly-line polyketide synthases (pkss) that produce biologically active natural products. we developed an automated method to extract and consolidate all multimodular pks sequences (including hybrid pks/non-ribosomal peptide synthetases) in the national center for biotechnology information (ncbi) database, generating a non-redundant catalog of 885 distinct assembly-line pkss, the majority of which were ...201324301183
characteristics of polygalacturonate lyase c from bacillus subtilis 7-3-3 and its synergistic action with pela in enzymatic degumming.an alkaline polygalacturonate lyase (pgl) from bacillus subtilis 7-3-3, pelc, with diverse depolymerization abilities for different pectin substrates was found. the pgl activity of pelc decreased with increasing degree of methyl esterification of the substrate. pela and pelc displayed notable synergistic effects in the enzymatic degumming of ramie fibers. gum loss rates increased by 62% when pelc was used to replace up to three-eighths of the pela dose (pelc, 60 u g(-1) ramie fibers). to the bes ...201324236123
rhizosphere microbiome assemblage is affected by plant development.there is a concerted understanding of the ability of root exudates to influence the structure of rhizosphere microbial communities. however, our knowledge of the connection between plant development, root exudation and microbiome assemblage is limited. here, we analyzed the structure of the rhizospheric bacterial community associated with arabidopsis at four time points corresponding to distinct stages of plant development: seedling, vegetative, bolting and flowering. overall, there were no sign ...201324196324
rhizosphere microbiome assemblage is affected by plant development.there is a concerted understanding of the ability of root exudates to influence the structure of rhizosphere microbial communities. however, our knowledge of the connection between plant development, root exudation and microbiome assemblage is limited. here, we analyzed the structure of the rhizospheric bacterial community associated with arabidopsis at four time points corresponding to distinct stages of plant development: seedling, vegetative, bolting and flowering. overall, there were no sign ...201324196324
synthesis of c11-desmethoxy soraphen a1α: a natural product analog that inhibits acetyl-coa carboxylase.a synthesis of c11-desmethoxy soraphen a1α is described that proceeds in just 14 steps from readily available starting materials. this natural product analog was identified as a target of interest in a program aimed at identifying novel natural product-inspired inhibitors of acetyl-coa carboxylase (acc) as potential anticancer therapeutics. while describing the most efficient synthesis of a soraphen a1α analog (total syntheses of the natural product have been reported that proceed in 25 to ≥40 l ...201324639892
a potential source for cellulolytic enzyme discovery and environmental aspects revealed through metagenomics of brazilian mangroves.the mangroves are among the most productive and biologically important environments. the possible presence of cellulolytic enzymes and microorganisms useful for biomass degradation as well as taxonomic and functional aspects of two brazilian mangroves were evaluated using cultivation and metagenomic approaches. from a total of 296 microorganisms with visual differences in colony morphology and growth (including bacteria, yeast and filamentous fungus), 179 (60.5%) and 117 (39.5%) were isolated fr ...201324160319
dna assembly techniques for next-generation combinatorial biosynthesis of natural products.natural product scaffolds remain important leads for pharmaceutical development. however, transforming a natural product into a drug entity often requires derivatization to enhance the compound's therapeutic properties. a powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. while these manipulations have traditionally been carried out via restriction digesti ...201324127070
dna assembly techniques for next-generation combinatorial biosynthesis of natural products.natural product scaffolds remain important leads for pharmaceutical development. however, transforming a natural product into a drug entity often requires derivatization to enhance the compound's therapeutic properties. a powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. while these manipulations have traditionally been carried out via restriction digesti ...201324127070
high-level expression of a novel thermostable and mannose-tolerant β-mannosidase from thermotoga thermarum dsm 5069 in escherichia coli.mannan is one of the primary polysaccharides in hemicellulose and is widely distributed in plants. β-mannosidase is an important constituent of the mannan-degrading enzyme system and it plays an important role in many industrial applications, such as food, feed and pulp/paper industries as well as the production of second generation bio-fuel. therefore, the mannose-tolerant β-mannosidase with high catalytic efficiency for bioconversion of mannan has a great potential in the fields as above.201324099409
class iii β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel.critics have suggested that neoadjuvant chemotherapy (nact) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. class iii β-tubulin overexpression has been linked to chemoresistance and hypoxia. herein, we describe changes in class iii β-tubulin in patients with advanced ovarian carcinoma in response to nact, in relationship to clinical outcome, and between ...201324005572
class iii β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel.critics have suggested that neoadjuvant chemotherapy (nact) followed by interval debulking may select for resistant clones or cancer stem cells when compared to primary cytoreduction. β-tubulins are chemotherapeutic targets of taxanes and epothilones. class iii β-tubulin overexpression has been linked to chemoresistance and hypoxia. herein, we describe changes in class iii β-tubulin in patients with advanced ovarian carcinoma in response to nact, in relationship to clinical outcome, and between ...201324005572
a markovian analysis of bacterial genome sequence constraints.the arrangement of nucleotides within a bacterial chromosome is influenced by numerous factors. the degeneracy of the third codon within each reading frame allows some flexibility of nucleotide selection; however, the third nucleotide in the triplet of each codon is at least partly determined by the preceding two. this is most evident in organisms with a strong g + c bias, as the degenerate codon must contribute disproportionately to maintaining that bias. therefore, a correlation exists between ...201324010012
interactions in the microbiome: communities of organisms and communities of genes.a central challenge in microbial community ecology is the delineation of appropriate units of biodiversity, which can be taxonomic, phylogenetic, or functional in nature. the term 'community' is applied ambiguously; in some cases, the term refers simply to a set of observed entities, while in other cases, it requires that these entities interact with one another. microorganisms can rapidly gain and lose genes, potentially decoupling community roles from taxonomic and phylogenetic groupings. trai ...201323909933
interactions in the microbiome: communities of organisms and communities of genes.a central challenge in microbial community ecology is the delineation of appropriate units of biodiversity, which can be taxonomic, phylogenetic, or functional in nature. the term 'community' is applied ambiguously; in some cases, the term refers simply to a set of observed entities, while in other cases, it requires that these entities interact with one another. microorganisms can rapidly gain and lose genes, potentially decoupling community roles from taxonomic and phylogenetic groupings. trai ...201323909933
a reductive coupling strategy towards ripostatin a.synthetic studies on the antibiotic natural product ripostatin a have been carried out with the aim to construct the c9-c10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. a cyclopropyl enyne fragment corresponding to c1-c9 has been synthesized in high yield and demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide ...201323946853
scalable metagenomic taxonomy classification using a reference genome database.deep metagenomic sequencing of biological samples has the potential to recover otherwise difficult-to-detect microorganisms and accurately characterize biological samples with limited prior knowledge of sample contents. existing metagenomic taxonomic classification algorithms, however, do not scale well to analyze large metagenomic datasets, and balancing classification accuracy with computational efficiency presents a fundamental challenge.201323828782
structure diversity of nitric oxide synthases (nos): the emergence of new forms in photosynthetic organisms. 201323847637
treatment of neuroblastoma and rhabdomyosarcoma using rgd-modified liposomal formulations of patupilone (epo906).patupilone (epo906) is a microtubule stabilizer with a potent antitumor effect. integrin αvβ3-binding (rgd) liposomes were loaded with epo906, and their antitumor efficacy was evaluated in two pediatric tumor models, ie, neuroblastoma and rhabdomyosarcoma.201323818777
anthracimycin, a potent anthrax antibiotic from a marine-derived actinomycete.licensed to kill: a new antibiotic, anthracimycin (see scheme), produced by a marine-derived actinomycete in saline culture, shows significant activity toward bacillus anthracis, the bacterial pathogen responsible for anthrax infections. chlorination of anthracimycin gives a dichloro derivative that retains activity against gram-positive bacteria, such as anthrax, but also shows activity against selected gram-negative bacteria.201323776159
tubulin-β-iii overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones.uterine serous carcinoma (usc) is a subtype of endometrial cancer associated with chemoresistance and poor outcome. overexpression of tubulin-β-iii and p-glycoprotein has been linked to paclitaxel resistance in many cancers but has been undercharacterized among uscs. epothilones have demonstrated activity in certain paclitaxel-resistant malignancies. in this study, relationships are clarified, in uscs relative to ovarian serous carcinomas (oscs), between tubulin-β-iii and p-glycoprotein expressi ...201323585021
molecular cloning, expression of mind gene from lactobacillus acidophilus vtcc-b-871 and analyses to identify lactobacillus rhamnosus pn04 from vietnam hottuynia cordata thunb.the mind gene encoding an inhibitor cell division mind homolog from lactobacillus acidophilus vtcc-b-871 was cloned. we showed that there were 97 % homology between mind genes of l. acidophilus vtcc-b-871 and lactobacillus rhamnosus gg and lactobacillus rhamnosus lc705. based on the analysis of the dna sequence data from the l. rhamnosus genome project and sequenced mind gene of l. acidophilus vtcc-b-871, a pair of primers was designed to identified the different mind genes from l. acidophilus a ...201324426140
the structure of a streptomyces avermitilis α-l-rhamnosidase reveals a novel carbohydrate-binding module cbm67 within the six-domain arrangement.α-l-rhamnosidases hydrolyze α-linked l-rhamnosides from oligosaccharides or polysaccharides. we determined the crystal structure of the glycoside hydrolase family 78 streptomyces avermitilis α-l-rhamnosidase (sarha78a) in its free and l-rhamnose complexed forms, which revealed the presence of six domains n, d, e, f, a, and c. in the ligand complex, l-rhamnose was bound in the proposed active site of the catalytic module, revealing the likely catalytic mechanism of sarha78a. glu(636) is predicted ...201323486481
chemotherapy in patients with anthracycline- and taxane-pretreated metastatic breast cancer: an overview.anthracyclines and taxanes are cytotoxic agents that are commonly used for the treatment of breast cancer, including in the adjuvant, neoadjuvant, and metastatic setting. each drug class of is associated with cumulative and potentially irreversible toxicity, including cardiomyopathy (anthracyclines) and neuropathy (taxanes). this may either limit the duration of therapy for advanced disease, or prevent retreatment for recurrence if previously used as component of adjuvant or neoadjuvant therapy. ...201323440080
new-old hemoglobin-like proteins of symbiotic dinoflagellates.symbiotic dinoflagellates are unicellular photosynthetic algae that live in mutualistic symbioses with many marine organisms. within the transcriptome of coral endosymbionts symbiodinium sp. (type c3), we discovered the sequences of two novel and highly polymorphic hemoglobin-like genes and proposed their 3d protein structures. at the protein level, four isoforms shared between 87 and 97% sequence identity for hb-1 and 78-99% for hb-2, whereas between hb-1 and hb-2 proteins, only 15-21% sequence ...201323610627
a general framework of persistence strategies for biological systems helps explain domains of life.the nature and cause of the division of organisms in superkingdoms is not fully understood. assuming that environment shapes physiology, here we construct a novel theoretical framework that helps identify general patterns of organism persistence. this framework is based on jacob von uexküll's organism-centric view of the environment and james g. miller's view of organisms as matter-energy-information processing molecular machines. three concepts describe an organism's environmental niche: scope, ...201323443991
locoregional interaction of ixabepilone (ixempra) after breast cancer radiation.radiation recall is an acute inflammatory reaction within a previously irradiated field triggered by chemotherapy administration. we observed a series of patients with unexpectedly severe reactions that included radiation recall and delayed healing when patients received the microtubule stabilizer ixabepilone (ixempra; bristol-myers squibb, princeton, nj) after radiation. we therefore decided to evaluate our experience in patients receiving ixabepilone following radiotherapy.201323404814
fungal exopolysaccharide: production, composition and applications.fungal exopolysaccharides (epss) have been recognized as high value biomacromolecules for the last two decades. these products, including pullulan, scleroglucan, and botryosphaeran, have several applications in industries, pharmaceuticals, medicine, foods etc. although fungal epss are highly relevant, to date information concerning fungal biosynthesis is scarce and an extensive search for new fugal species that can produce novel epss is still needed. in most cases, the molecular weight variation ...201324826070
integron gene cassettes: a repository of novel protein folds with distinct interaction sites.mobile gene cassettes captured within integron arrays encompass a vast and diverse pool of genetic novelty. in most cases, functional annotation of gene cassettes directly recovered by cassette-pcr is obscured by their characteristically high sequence novelty. this inhibits identification of those specific functions or biological features that might constitute preferential factors for lateral gene transfer via the integron system. a structural genomics approach incorporating x-ray crystallograph ...201323349695
boronated tartrolon antibiotic produced by symbiotic cellulose-degrading bacteria in shipworm gills.shipworms are marine wood-boring bivalve mollusks (family teredinidae) that harbor a community of closely related gammaproteobacteria as intracellular endosymbionts in their gills. these symbionts have been proposed to assist the shipworm host in cellulose digestion and have been shown to play a role in nitrogen fixation. the genome of one strain of teredinibacter turnerae, the first shipworm symbiont to be cultivated, was sequenced, revealing potential as a rich source of polyketides and nonrib ...201323288898
ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature.this review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (ripps), a rapidly growing class of natural products. the current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.201323165928
marine actinobacteria from the gulf of california: diversity, abundance and secondary metabolite biosynthetic potential.the gulf of california is a coastal marine ecosystem characterized as having abundant biological resources and a high level of endemism. in this work we report the isolation and characterization of actinobacteria from different sites in the western gulf of california. we collected 126 sediment samples and isolated on average 3.1-38.3 actinobacterial strains from each sample. phylogenetic analysis of 136 strains identified them as members of the genera actinomadura, micromonospora, nocardiopsis, ...201323229438
marine actinobacteria from the gulf of california: diversity, abundance and secondary metabolite biosynthetic potential.the gulf of california is a coastal marine ecosystem characterized as having abundant biological resources and a high level of endemism. in this work we report the isolation and characterization of actinobacteria from different sites in the western gulf of california. we collected 126 sediment samples and isolated on average 3.1-38.3 actinobacterial strains from each sample. phylogenetic analysis of 136 strains identified them as members of the genera actinomadura, micromonospora, nocardiopsis, ...201323229438
identification of myxobacteria-derived hiv inhibitors by a high-throughput two-step infectivity assay.drug-resistance and therapy failure due to drug-drug interactions are the main challenges in current treatment against human immunodeficiency virus (hiv) infection. as such, there is a continuous need for the development of new and more potent anti-hiv drugs. here we established a high-throughput screen based on the highly permissive tzm-bl cell line to identify novel hiv inhibitors. the assay allows discriminating compounds acting on early and/or late steps of the hiv replication cycle.201324063434
ppgpp metabolism is involved in heterocyst development in the cyanobacterium anabaena sp. strain pcc 7120.when deprived of a combined-nitrogen source in the growth medium, the filamentous cyanobacterium anabaena sp. pcc 7120 (anabaena) can form heterocysts capable of nitrogen fixation. the process of heterocyst differentiation takes about 20 to 24 h, during which extensive metabolic and morphological changes take place. guanosine tetraphosphate (ppgpp) is the signal of the stringent response that ensures cell survival by adjusting major cellular activities in response to nutrient starvation in bacte ...201323935047
characterization of four type iv pilin homologues in stigmatella aurantiaca dsm17044 by heterologous expression in myxococcus xanthus.as prokaryotic models for multicellular development, stigmatella aurantiaca and myxococcus xanthus share many similarities in terms of social behaviors, such as gliding motility. our current understanding of myxobacterial grouped-cell motilities comes mainly from the research on m. xanthus, which shows that filamentous type iv pili (tfp), composed of type iv pilin (also called pila protein) subunits, are the key apparatus for social motility (s-motility). however, little is known about the pilin ...201324058653
engineering microbial cells for the biosynthesis of natural compounds of pharmaceutical significance.microbes constitute important platforms for the biosynthesis of numerous molecules of pharmaceutical interest such as antitumor, anticancer, antiviral, antihypertensive, antiparasitic, antioxidant, immunological agents, and antibiotics as well as hormones, belonging to various chemical families, for instance, terpenoids, alkaloids, polyphenols, polyketides, amines, and proteins. engineering microbial factories offers rich opportunities for the production of natural products that are too complex ...201323710459
complete genome sequence of myxococcus stipitatus strain dsm 14675, a fruiting myxobacterium.hallmarks of the myxobacteria include the formation of spore-filled fruiting bodies in response to starvation and synthesis of secondary metabolites. myxococcus stipitatus forms morphologically highly distinct fruiting bodies and produces secondary metabolites with antibiotic or cytotoxic activities. here, we present the 10.35-mb genome sequence of m. stipitatus strain dsm 14675.201323516218
natural products: a continuing source of novel drug leads.nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from nature to the laboratory bench.201323428572
isolation and identification of myxobacteria from saline-alkaline soils in xinjiang, china.fifty-eight terrestrial and salt-tolerant myxobacteria were isolated from the saline-alkaline soils collected from xinjiang, china. based on the morphologies and the 16s rrna gene sequences, these isolates were assigned into 6 genera, myxococcus, cystobacter, corallococcus, sorangium, nannocystis and polyangium. all the strains grew better with 1% nacl than without nacl. some myxococcus strains were able to grow at 2% nacl concentration, suggesting that these strains may be particular type of te ...201323936436
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
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
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
a view to a kill: the bacterial type vi secretion system.the bacterial type vi secretion system (t6ss) is an organelle that is structurally and mechanistically analogous to an intracellular membrane-attached contractile phage tail. recent studies determined that a rapid conformational change in the structure of a sheath protein complex propels t6ss spike and tube components along with antibacterial and antieukaryotic effectors out of predatory t6ss(+) cells and into prey cells. the contracted organelle is then recycled in an atp-dependent process. t6s ...201324332978
a view to a kill: the bacterial type vi secretion system.the bacterial type vi secretion system (t6ss) is an organelle that is structurally and mechanistically analogous to an intracellular membrane-attached contractile phage tail. recent studies determined that a rapid conformational change in the structure of a sheath protein complex propels t6ss spike and tube components along with antibacterial and antieukaryotic effectors out of predatory t6ss(+) cells and into prey cells. the contracted organelle is then recycled in an atp-dependent process. t6s ...201324332978
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
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
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
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
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
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
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
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
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
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
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
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
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
a small predatory core genome in the divergent marine bacteriovorax marinus sj and the terrestrial bdellovibrio bacteriovorus.bacteriovorax marinus sj is a predatory delta-proteobacterium isolated from a marine environment. the genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium bdellovibrio bacteriovorus hd100. based on their predatory lifestyle, bacteriovorax were originally designated as members of the genus bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. b. marinus attaches to gram-negati ...201222955231
a small predatory core genome in the divergent marine bacteriovorax marinus sj and the terrestrial bdellovibrio bacteriovorus.bacteriovorax marinus sj is a predatory delta-proteobacterium isolated from a marine environment. the genome sequence of this strain provides an interesting contrast to that of the terrestrial predatory bacterium bdellovibrio bacteriovorus hd100. based on their predatory lifestyle, bacteriovorax were originally designated as members of the genus bdellovibrio but subsequently were re-assigned to a new genus and family based on genetic and phenotypic differences. b. marinus attaches to gram-negati ...201222955231
intra- and interprotein phosphorylation between two-hybrid histidine kinases controls myxococcus xanthus developmental progression.histidine-aspartate phosphorelay signaling systems are used to couple stimuli to cellular responses. a hallmark feature is the highly modular signal transmission modules that can form both simple "two-component" systems and sophisticated multicomponent systems that integrate stimuli over time and space to generate coordinated and fine-tuned responses. the deltaproteobacterium myxococcus xanthus contains a large repertoire of signaling proteins, many of which regulate its multicellular developmen ...201222661709
complete genome sequence of the fruiting myxobacterium corallococcus coralloides dsm 2259.corallococcus coralloides, like most other myxobacteria, undergoes a developmental program culminating in the formation of fruiting bodies. c. coralloides fruiting bodies are morphologically distinct from those of other fruiting myxobacteria for which full-length genome sequences are available. the genome sequence of the 10.0-mb c. coralloides genome is presented herein.201222582372
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