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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
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 low abundance microbiome in clinical samples using whole genome sequencing.identifying the microbiome composition from primary tissues directly affords an opportunity to study the causative relationships between the host microbiome and disease. however, this is challenging due the low abundance of microbial dna relative to the host. we present a systematic evaluation of microbiome profiling directly from endoscopic biopsies by whole genome sequencing. we compared our methods with other approaches on datasets with previously identified microbial composition. we applied ...201526614063
functional dichotomy in the 16s rrna (m1a1408) methyltransferase family and control of catalytic activity via a novel tryptophan mediated loop reorganization.methylation of the bacterial small ribosomal subunit (16s) rrna on the n1 position of a1408 confers exceptionally high-level resistance to a broad spectrum of aminoglycoside antibiotics. here, we present a detailed structural and functional analysis of the catenulisporales acidiphilia 16s rrna (m(1)a1408) methyltransferase ('cackam'). the apo cackam structure closely resembles other m(1)a1408 methyltransferases within its conserved sam-binding fold but the region linking core β strands 6 and 7 ( ...201526609134
functional dichotomy in the 16s rrna (m1a1408) methyltransferase family and control of catalytic activity via a novel tryptophan mediated loop reorganization.methylation of the bacterial small ribosomal subunit (16s) rrna on the n1 position of a1408 confers exceptionally high-level resistance to a broad spectrum of aminoglycoside antibiotics. here, we present a detailed structural and functional analysis of the catenulisporales acidiphilia 16s rrna (m(1)a1408) methyltransferase ('cackam'). the apo cackam structure closely resembles other m(1)a1408 methyltransferases within its conserved sam-binding fold but the region linking core β strands 6 and 7 ( ...201526609134
hgtree: database of horizontally transferred genes determined by tree reconciliation.the hgtree database provides putative genome-wide horizontal gene transfer (hgt) information for 2472 completely sequenced prokaryotic genomes. this task is accomplished by reconstructing approximate maximum likelihood phylogenetic trees for each orthologous gene and corresponding 16s rrna reference species sets and then reconciling the two trees under parsimony framework. the tree reconciliation method is generally considered to be a reliable way to detect hgt events but its practical use has r ...201526578597
hgtree: database of horizontally transferred genes determined by tree reconciliation.the hgtree database provides putative genome-wide horizontal gene transfer (hgt) information for 2472 completely sequenced prokaryotic genomes. this task is accomplished by reconstructing approximate maximum likelihood phylogenetic trees for each orthologous gene and corresponding 16s rrna reference species sets and then reconciling the two trees under parsimony framework. the tree reconciliation method is generally considered to be a reliable way to detect hgt events but its practical use has r ...201526578597
the pathogen-derived aminoglycoside resistance 16s rrna methyltransferase npma possesses dual m1a1408/m1g1408 specificity.chemical modification of 16s rrna can confer exceptionally high-level resistance to a diverse set of aminoglycoside antibiotics. here, we show that the pathogen-derived enzyme npma possesses dual m(1)a1408/m(1)g1408 activity, an unexpected property apparently unique among the known aminoglycoside resistance 16s rrna (m(1)a1408) methyltransferases. although the biological significance of this activity remains to be determined, such mechanistic variation in enzymes acquired by pathogens has signif ...201526416864
recent advances in the development of antineoplastic agents derived from natural products.through years of evolutionary selection pressures, organisms have developed potent toxins that coincidentally have marked antineoplastic activity. these natural products have been vital for the development of multiagent treatment regimens currently employed in cancer chemotherapy, and are used in the treatment of a variety of malignancies. therefore, this review catalogs recent advances in natural product-based drug discovery via the examination of mechanisms of action and available clinical dat ...201526501980
bis-cyclopropane analog of disorazole c1 is a microtubule-destabilizing agent active in abcb1-overexpressing human colon cancer cells.the novel, chemically stabilized disorazole analog, (-)-cp2-disorazole c1 (1) displayed potent anti-proliferative activity against a broad-spectrum of human colorectal cancer cells. hct15 and h630r1 cell lines expressing high basal levels of the abcb1 protein, known to cause multi-drug resistance, were also sensitive to growth inhibition by 1 but were resistant to both vincristine and docetaxel, two commonly used microtubule inhibitors. compound 1 exhibited strong inhibition of tubulin polymeriz ...201526506423
highly efficient cyp167a1 (epok) dependent epothilone b formation and production of 7-ketone epothilone d as a new epothilone derivative.since their discovery in the soil bacterium sorangium cellulosum, epothilones have emerged as a valuable substance class with promising anti-tumor activity. because of their benefits in the treatment of cancer and neurodegenerative diseases, epothilones are targets for drug design and pharmaceutical research. the final step of their biosynthesis - a cytochrome p450 mediated epoxidation of epothilone c/d to a/b by cyp167a1 (epok) - needs significant improvement, in particular regarding the effici ...201526445909
well-known surface and extracellular antigens of pathogenic microorganisms among the immunodominant proteins of the infectious microalgae prototheca zopfii.microalgae of the genus prototheca (p.) are associated with rare but severe infections (protothecosis) and represent a potential zoonotic risk. genotype (gt) 2 of p. zopfii has been established as pathogenic agent for humans, dogs, and cattle, whereas gt1 is considered to be non-pathogenic. since pathogenesis is poorly understood, the aim of this study was to determine immunogenic proteins and potential virulence factors of p. zopfii gt2. therefore, 2d western blot analyses with sera and isolate ...201526484314
structural basis of targeting the exportin crm1 in cancer.recent studies have demonstrated the interference of nucleocytoplasmic trafficking with the establishment and maintenance of various cancers. nucleocytoplasmic transport is highly regulated and coordinated, involving different nuclear transport factors or receptors, importins and exportins, that mediate cargo transport from the cytoplasm into the nucleus or the other way round, respectively. the exportin crm1 (chromosome region maintenance 1) exports a plethora of different protein cargoes and r ...201526402707
metabolic coevolution in the bacterial symbiosis of whiteflies and related plant sap-feeding insects.genomic decay is a common feature of intracellular bacteria that have entered into symbiosis with plant sap-feeding insects. this study of the whitefly bemisia tabaci and two bacteria (portiera aleyrodidarum and hamiltonella defensa) cohoused in each host cell investigated whether the decay of portiera metabolism genes is complemented by host and hamiltonella genes, and compared the metabolic traits of the whitefly symbiosis with other sap-feeding insects (aphids, psyllids, and mealybugs). paral ...201526377567
strategies for the optimization of natural leads to anticancer drugs or drug candidates.natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. more often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve absorption, distr ...201526359649
strategies for the optimization of natural leads to anticancer drugs or drug candidates.natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. more often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve absorption, distr ...201526359649
from gene to biorefinery: microbial β-etherases as promising biocatalysts for lignin valorization.the set-up of biorefineries for the valorization of lignocellulosic biomass will be core in the future to reach sustainability targets. in this area, biomass-degrading enzymes are attracting significant research interest for their potential in the production of chemicals and biofuels from renewable feedstock. glutathione-dependent β-etherases are emerging enzymes for the biocatalytic depolymerization of lignin, a heterogeneous aromatic polymer abundant in nature. they selectively catalyze the re ...201526388858
conformation-activity relationships of polyketide natural products.polyketides represent an important class of secondary metabolites that interact with biological targets connected to a variety of disease-associated pathways. remarkably, nature's assembly lines, polyketide synthases, manufacture these privileged structures through a combinatorial mixture of just a few structural units. this review highlights the role of these structural elements in shaping a polyketide's conformational preferences, the use of computer-based molecular modeling and solution nmr s ...201525974024
the origin and evolution of baeyer-villiger monooxygenases (bvmos): an ancestral family of flavin monooxygenases.the baeyer-villiger monooxygenases (bvmos) are enzymes belonging to the "class b" of flavin monooxygenases and are capable of performing exquisite selective oxidations. these enzymes have been studied from a biotechnological perspective, but their physiological substrates and functional roles are widely unknown. here, we investigated the origin, taxonomic distribution and evolutionary history of the bvmo genes. by using in silico approaches, 98 bvmo encoding genes were detected in the three doma ...201526161776
the complex relationship between microbial growth rate and yield and its implications for ecosystem processes. 201526136742
expression, function, and targeting of the nuclear exporter chromosome region maintenance 1 (crm1) protein.nucleocytoplasmic trafficking of proteins/rnas is essential to normal cellular function. indeed, accumulating evidence suggests that cancer cells escape anti-neoplastic mechanisms and benefit from pro-survival signals via the dysregulation of this system. the nuclear exporter chromosome region maintenance 1 (crm1) protein is the only protein in the karyopherin-β protein family that contributes to the trafficking of numerous proteins and rnas from the nucleus. it is considered to be an oncogenic, ...201526048327
nitric oxide mediates biofilm formation and symbiosis in silicibacter sp. strain trichch4b.nitric oxide (no) plays an important signaling role in all domains of life. many bacteria contain a heme-nitric oxide/oxygen binding (h-nox) protein that selectively binds no. these h-nox proteins often act as sensors that regulate histidine kinase (hk) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. in several organisms, no binding to the h-nox protein governs bacterial biofilm formation; however, the source of no exposure ...201525944856
self-assembly of disorazole c1 through a one-pot alkyne metathesis homodimerization strategy.alkyne metathesis is increasingly explored as a reliable method to close macrocyclic rings, but there are no prior examples of an alkyne-metathesis-based homodimerization approach to natural products. in this approach to the cytotoxic c2 -symmetric marine-derived bis(lactone) disorazole c1, a highly convergent, modular strategy is employed featuring cyclization through an ambitious one-pot alkyne cross-metathesis/ring-closing metathesis self-assembly process.201527346897
self-assembly of disorazole c1 through a one-pot alkyne metathesis homodimerization strategy.alkyne metathesis is increasingly explored as a reliable method to close macrocyclic rings, but there are no prior examples of an alkyne-metathesis-based homodimerization approach to natural products. in this approach to the cytotoxic c2-symmetric marine-derived bis(lactone) disorazole c1, a highly convergent, modular strategy is employed featuring cyclization through an ambitious one-pot alkyne cross-metathesis/ring-closing metathesis self-assembly process.201525926364
the composition of the global and feature specific cyanobacterial core-genomes.cyanobacteria are photosynthetic prokaryotes important for many ecosystems with a high potential for biotechnological usage e.g., in the production of bioactive molecules. either asks for a deep understanding of the functionality of cyanobacteria and their interaction with the environment. this in part can be inferred from the analysis of their genomes or proteomes. today, many cyanobacterial genomes have been sequenced and annotated. this information can be used to identify biological pathways ...201525852675
ccr 20th anniversary commentary: bms-247550—microtubule stabilization as successful targeted therapy.in a landmark article published in the may 1, 2001, issue of clinical cancer research, lee and colleagues reported the original preclinical studies demonstrating anticancer activity of bms-247550 (ixabepilone) against taxane-sensitive and taxane-resistant cancers. subsequent clinical trials established the clinical efficacy of ixabepilone, leading to its regulatory approval for the treatment of drug-resistant metastatic or locally advanced breast cancers.201525770292
large-scale 13c flux profiling reveals conservation of the entner-doudoroff pathway as a glycolytic strategy among marine bacteria that use glucose.marine bacteria form one of the largest living surfaces on earth, and their metabolic activity is of fundamental importance for global nutrient cycling. here, we explored the largely unknown intracellular pathways in 25 microbes representing different classes of marine bacteria that use glucose: alphaproteobacteria, gammaproteobacteria, and flavobacteriia of the bacteriodetes phylum. we used (13)c isotope experiments to infer metabolic fluxes through their carbon core pathways. notably, 90% of a ...201525616803
insights from 20 years of bacterial genome sequencing.since the first two complete bacterial genome sequences were published in 1995, the science of bacteria has dramatically changed. using third-generation dna sequencing, it is possible to completely sequence a bacterial genome in a few hours and identify some types of methylation sites along the genome as well. sequencing of bacterial genome sequences is now a standard procedure, and the information from tens of thousands of bacterial genomes has had a major impact on our views of the bacterial w ...201525722247
bacterial rna polymerase-dna interaction-the driving force of gene expression and the target for drug action.dna-dependent multisubunit rna polymerase (rnap) is the key enzyme of gene expression and a target of regulation in all kingdoms of life. it is a complex multifunctional molecular machine which, unlike other dna-binding proteins, engages in extensive and dynamic interactions (both specific and nonspecific) with dna, and maintains them over a distance. these interactions are controlled by dna sequences, dna topology, and a host of regulatory factors. here, we summarize key recent structural and b ...201627882317
expression and characterization of thermotolerant lipase with broad ph profiles isolated from an antarctic pseudomonas sp strain ams3.a gene encoding a thermotolerant lipase with broad ph was isolated from an antarctic pseudomonas strain ams3. the recombinant lipase ams3 was purified by single-step purification using affinity chromatography, yielding a purification fold of approximately 1.52 and a recovery of 50%. the molecular weight was approximately ∼60 kda including the strep and affinity tags. interestingly, the purified antarctic ams3 lipase exhibited broad temperature profile from 10-70 °c and stable over a broad ph ran ...201627781152
structural basis of steroid binding and oxidation by the cytochrome p450 cyp109e1 from bacillus megaterium.cytochrome p450 monooxygenases (p450s) are attractive enzymes for the pharmaceutical industry, in particular, for applications in steroidal drug synthesis. here, we report a comprehensive functional and structural characterization of cyp109e1, a novel steroid-converting cytochrome p450 enzyme identified from the genome of bacillus megaterium dsm319. in vitro and whole-cell in vivo turnover experiments, combined with binding assays, revealed that cyp109e1 is able to hydroxylate testosterone at po ...201627686671
discovery, molecular mechanisms, and industrial applications of cold-active enzymes.cold-active enzymes constitute an attractive resource for biotechnological applications. their high catalytic activity at temperatures below 25°c makes them excellent biocatalysts that eliminate the need of heating processes hampering the quality, sustainability, and cost-effectiveness of industrial production. here we provide a review of the isolation and characterization of novel cold-active enzymes from microorganisms inhabiting different environments, including a revision of the latest techn ...201627667987
mechanistic investigations on six bacterial terpene cyclases.the products obtained by incubation of farnesyl diphosphate (fpp) with six purified bacterial terpene cyclases were characterised by one- and two-dimensional nmr spectroscopic methods, allowing for a full structure elucidation. the absolute configurations of four terpenes were determined based on their optical rotary powers. incubation experiments with (13)c-labelled isotopomers of fpp in buffers containing water or deuterium oxide allowed for detailed insights into the cyclisation mechanisms of ...201627829890
winding paths to simplicity: genome evolution in facultative insect symbionts.symbiosis between organisms is an important driving force in evolution. among the diverse relationships described, extensive progress has been made in insect-bacteria symbiosis, which improved our understanding of the genome evolution in host-associated bacteria. particularly, investigations on several obligate mutualists have pushed the limits of what we know about the minimal genomes for sustaining cellular life. to bridge the gap between those obligate symbionts with extremely reduced genomes ...201627519426
phase ii trial of utidelone as monotherapy or in combination with capecitabine in heavily pretreated metastatic breast cancer patients.the treatment of metastatic breast cancer (mbc) remains a great clinical challenge as drug resistance frequently develops. alternative agents that can overcome drug resistance would offer new therapeutic options. the primary aim of this phase ii study was to evaluate the efficacy and safety of utidelone as a monotherapy or in combination with capecitabine in metastatic breast cancer patients previously treated with and resistant to anthracyclines and taxanes.201627516093
effects of organic-loading-rate reduction on sludge biomass and microbial community in a deteriorated pilot-scale membrane bioreactor.the effects of a precipitous decrease in the inlet organic loading rate on sludge reductions and the microbial community in a membrane bioreactor were investigated. the sludge biomass was markedly reduced to 47.4% of the initial concentration (approximately 15,000 mg l(-1)) within 7 d after the organic loading rate was decreased by half (450 to 225 mg chemical oxygen demand l(-1) d(-1)). an analysis of the microbial community structure using high-throughput sequencing revealed an increase in the ...201627431196
the biofilm inhibitor carolacton inhibits planktonic growth of virulent pneumococci via a conserved target.new antibacterial compounds, preferentially exploiting novel cellular targets, are urgently needed to fight the increasing resistance of pathogens against conventional antibiotics. here we demonstrate that carolacton, a myxobacterial secondary metabolite previously shown to damage streptococcus mutans biofilms, inhibits planktonic growth of streptococcus pneumoniae tigr4 and multidrug-resistant clinical isolates of serotype 19a at nanomolar concentrations. a carolacton diastereomer is inactive i ...201627404808
metagenomic discovery of novel enzymes and biosurfactants in a slaughterhouse biofilm microbial community.dna derived from environmental samples is a rich source of novel bioactive molecules. the choice of the habitat to be sampled predefines the properties of the biomolecules to be discovered due to the physiological adaptation of the microbial community to the prevailing environmental conditions. we have constructed a metagenomic library in escherichia coli dh10b with environmental dna (edna) isolated from the microbial community of a slaughterhouse drain biofilm consisting mainly of species from ...201627271534
epothilones suppress neointimal thickening in the rat carotid balloon-injury model by inducing vascular smooth muscle cell apoptosis through p53-dependent signaling pathway.microtubule stabilizing agents (mtsa) are known to inhibit vascular smooth muscle cell (vsmc) proliferation and migration, and effectively reduce neointimal hyperplasia and restenosis. epothilones (epos), non-taxane mtsa, have been found to be effective in the inhibition of vsmc proliferation and neointimal formation by cell cycle arrest. however, effect of epos on apoptosis in hyper-proliferated vsmcs as a possible way to reduce neointimal formation and its action mechanism related to vsmc viab ...201627218463
bacterial long-chain polyunsaturated fatty acids: their biosynthetic genes, functions, and practical use.the nutritional and pharmaceutical values of long-chain polyunsaturated fatty acids (lc-pufas) such as arachidonic, eicosapentaenoic and docosahexaenoic acids have been well recognized. these lc-pufas are physiologically important compounds in bacteria and eukaryotes. although little is known about the biosynthetic mechanisms and functions of lc-pufas in bacteria compared to those in higher organisms, a combination of genetic, bioinformatic, and molecular biological approaches to lc-pufa-produci ...201627187420
rhodotorula glutinis phenylalanine/tyrosine ammonia lyase enzyme catalyzed synthesis of the methyl ester of para-hydroxycinnamic acid and its potential antibacterial activity.biotransformation of l-tyrosine methyl ester (l-tm) to the methyl ester of para- hydroxycinnamic acid (p-hcam) using rhodotorula glutinis yeast phenylalanine/tyrosine ammonia lyase (ptal; ec 4.3.1.26) enzyme was successfully demonstrated for the first time; progress of the reaction was followed by spectrophotometric determination at 315 nm. the following conditions were optimized for maximal formation of p-hcam: ph (8.5), temperature (37°c), speed of agitation (50 rpm), enzyme concentration (0.0 ...201627014206
implications for public health demands alternatives to inorganic and synthetic flocculants: bioflocculants as important candidates.chemical flocculants are generally used in drinking water and wastewater treatment due to their efficacy and cost effectiveness. however, the question of their toxicity to human health and environmental pollution has been a major concern. in this article, we review the application of some chemical flocculants utilized in water treatment, and bioflocculants as a potential alternative to these chemical flocculants. to the best of our knowledge, there is no report in the literature that provides an ...201626914994
structure-based analysis of the molecular interactions between acyltransferase and acyl carrier protein in vicenistatin biosynthesis.acyltransferases (ats) are key determinants of building block specificity in polyketide biosynthesis. despite the importance of protein-protein interactions between at and acyl carrier protein (acp) during the acyltransfer reaction, the mechanism of acp recognition by at is not understood in detail. herein, we report the crystal structure of at vink, which transfers a dipeptide group between two acps, vinl and vinp1ldacp, in vicenistatin biosynthesis. the isolated vink structure showed a unique ...201626831085
discovery of cahuitamycins as biofilm inhibitors derived from a convergent biosynthetic pathway.pathogenic microorganisms often have the ability to attach to a surface, building a complex matrix where they colonize to form a biofilm. this cellular superstructure can display increased resistance to antibiotics and cause serious, persistent health problems in humans. here we describe a high-throughput in vitro screen to identify inhibitors of acinetobacter baumannii biofilms using a library of natural product extracts derived from marine microbes. analysis of extracts derived from streptomyc ...201626880271
the effector candidate repertoire of the arbuscular mycorrhizal fungus rhizophagus clarus.arbuscular mycorrhizal fungi (amf) form an ecologically important symbiosis with more than two thirds of studied land plants. recent studies of plant-pathogen interactions showed that effector proteins play a key role in host colonization by controlling the plant immune system. we hypothesise that also for symbiotic-plant interactions the secreted effectome of the fungus is a major component of communication and the conservation level of effector proteins between amf species may be indicative wh ...201626861502
the antibody catalysis route to the total synthesis of epothilones.an efficient monoclonal aldolase antibody that proceeds by an enamine mechanism was generated by reactive immunization. here, this catalyst has been used in the total synthesis of epothilones a (1) and c (3). the starting materials for the synthesis of these molecules have been obtained by using antibody-catalyzed aldol and retro-aldol reactions. these precursors were then converted to epothilones a (1) and c (3) to complete the total synthesis.19989843936
total synthesis of epothilones b and d: stannane equivalents for beta-keto ester dianions.studies leading to a total synthesis of epothilones b and d are described. the overall synthetic plan was based on late-stage fragment assembly of two segments representing c(1)-c(9) and c(10)-c(21) of the structure. the c(1)-c(9) fragment was prepared by elaboration of commercially available (2r)-3-hydroxy-2-methylpropanoate at both ends of the three-carbon unit. introduction of carbons 1-4 containing the gem-dimethyl unit was achieved in a convergent manner using a diastereoselective addition ...200818991385
(+)-sorangicin a: evolution of a viable synthetic strategy.an effective, asymmetric total synthesis of the antibiotic (+)-sorangicin a (1) has been achieved. central to this venture was the development of first and second generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a co(2)(co)(6)-alkyne complex, the second involving a khmds-promoted epoxide ring formation/opening cascade. additional highlights include effective construction of the dihydro- and t ...201122247573
stabilized polymer micelles for the development of it-147, an epothilone d drug-loaded formulation.epothilones have demonstrated promising potential for oncology applications but suffer from a narrow therapeutic window. epothilone d stabilizes microtubules leading to apoptosis, is active against multidrug-resistant cells, and is efficacious in animal tumor models despite lack of stability in rodent plasma. clinical development was terminated in phase ii due to dose limiting toxicities near the efficacious dose. taken together, this made epothilone d attractive for encapsulation in a stabilize ...201628044108
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