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diversity of epothilone producers among sorangium strains in producer-positive soil habitats.large-scale surveys show that the anti-tumour compounds known as epothilones are produced by only a small proportion of sorangium strains, thereby greatly hampering the research and development of these valuable compounds. in this study, to investigate the niche diversity of epothilone-producing sorangium strains, we re-surveyed four soil samples where epothilone producers were previously found. compared with the < 2.5% positive strains collected from different places, epothilone producers compr ...201424308800
diversity of epothilone producers among sorangium strains in producer-positive soil habitats.large-scale surveys show that the anti-tumour compounds known as epothilones are produced by only a small proportion of sorangium strains, thereby greatly hampering the research and development of these valuable compounds. in this study, to investigate the niche diversity of epothilone-producing sorangium strains, we re-surveyed four soil samples where epothilone producers were previously found. compared with the < 2.5% positive strains collected from different places, epothilone producers compr ...201424308800
cyclic di-gmp regulates type iv pilus-dependent motility in myxococcus xanthus.the nucleotide-based second messenger bis-(3'-5')-cyclic dimeric gmp (c-di-gmp) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. myxococcus xanthus undergoes major lifestyle changes in response to nutrient availability, with the formation of spreading colonies in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. here, we investigated the function of c-di-gmp in m. xanthus and show that this b ...201526124238
cyclic di-gmp regulates type iv pilus-dependent motility in myxococcus xanthus.the nucleotide-based second messenger bis-(3'-5')-cyclic dimeric gmp (c-di-gmp) is involved in regulating a plethora of processes in bacteria that are typically associated with lifestyle changes. myxococcus xanthus undergoes major lifestyle changes in response to nutrient availability, with the formation of spreading colonies in the presence of nutrients and spore-filled fruiting bodies in the absence of nutrients. here, we investigated the function of c-di-gmp in m. xanthus and show that this b ...201526124238
genome-wide analysis of myxobacterial two-component systems: genome relatedness and evolutionary changes.two-component systems (tcss) are abundant prokaryotic signaling pathways, whose evolution is of particular importance because of their role in bacterial pathogenicity. comparative genomics can provide important insights into the evolution of these genes, but inferences are dependent on the relatedness of the compared genomes. this study investigated the relationship between evolutionary distance and tcs evolution in myxobacterial genomes, of which there are several sequenced examples, of varying ...201526463047
characterization of 3'-phosphate rna ligase paralogs rtcb1, rtcb2, and rtcb3 from myxococcus xanthus highlights dna and rna 5'-phosphate capping activity of rtcb3.escherichia coli rtcb exemplifies a family of gtp-dependent rna repair/splicing enzymes that join 3'-po4 ends to 5'-oh ends via stable rtcb-(histidinyl-n)-gmp and transient rna3'pp5'g intermediates. e. coli rtcb also transfers gmp to a dna 3'-po4 end to form a stable "capped" product, dna3'pp5'g. rtcb homologs are found in a multitude of bacterial proteomes, and many bacteria have genes encoding two or more rtcb paralogs; an extreme example is myxococcus xanthus, which has six rtcbs. in this stu ...201526350128
devi is an evolutionarily young negative regulator of myxococcus xanthus development.during starvation-induced development of myxococcus xanthus, thousands of rod-shaped cells form mounds in which they differentiate into spores. the dev locus includes eight genes followed by clustered regularly interspaced short palindromic repeats (crisprs), comprising a crispr-cas system (cas stands for crispr associated) typically involved in rna interference. mutations in devs or devr of a lab reference strain permit mound formation but impair sporulation. we report that natural isolates of ...201525645563
reinvigorating natural product combinatorial biosynthesis with synthetic biology.natural products continue to play a pivotal role in drug-discovery efforts and in the understanding if human health. the ability to extend nature's chemistry through combinatorial biosynthesis--altering functional groups, regiochemistry and scaffold backbones through the manipulation of biosynthetic enzymes--offers unique opportunities to create natural product analogs. incorporating emerging synthetic biology techniques has the potential to further accelerate the refinement of combinatorial bio ...201526284672
phylogenetic co-occurrence of exor, exos, and chvi, components of the rsi bacterial invasion switch, suggests a key adaptive mechanism regulating the transition between free-living and host-invading phases in rhizobiales.both bacterial symbionts and pathogens rely on their host-sensing mechanisms to activate the biosynthetic pathways necessary for their invasion into host cells. the gram-negative bacterium sinorhizobium meliloti relies on its rsi (exor-exos-chvi) invasion switch to turn on the production of succinoglycan, an exopolysaccharide required for its host invasion. recent whole-genome sequencing efforts have uncovered putative components of rsi-like invasion switches in many other symbiotic and pathogen ...201526309130
highly active and specific tyrosine ammonia-lyases from diverse origins enable enhanced production of aromatic compounds in bacteria and saccharomyces cerevisiae.phenylalanine and tyrosine ammonia-lyases form cinnamic acid and p-coumaric acid, which are precursors of a wide range of aromatic compounds of biotechnological interest. lack of highly active and specific tyrosine ammonia-lyases has previously been a limitation in metabolic engineering approaches. we therefore identified 22 sequences in silico using synteny information and aiming for sequence divergence. we performed a comparative in vivo study, expressing the genes intracellularly in bacteria ...201525911487
neutral and phospholipids of the myxococcus xanthus lipodome during fruiting body formation and germination.myxobacteria are well-known for their complex life cycle, including the formation of spore-filled fruiting bodies. the model organism myxococcus xanthus exhibits a highly complex composition of neutral and phospholipids, including triacylglycerols (tags), diacylglycerols (dags), phosphatidylethanolamines (pes), phosphatidylglycerols (pgs), cardiolipins (cls), and sphingolipids, including ceramides (cers) and ceramide phosphoinositols (cer-pis). in addition, ether lipids have been shown to be inv ...201526162876
allopatric integrations selectively change host transcriptomes, leading to varied expression efficiencies of exotic genes in myxococcus xanthus.exotic genes, especially clustered multiple-genes for a complex pathway, are normally integrated into chromosome for heterologous expression. the influences of insertion sites on heterologous expression and allotropic expressions of exotic genes on host remain mostly unclear.201526194479
pseudomonas putida-a versatile host for the production of natural products.the biosynthesis of natural products by heterologous expression of biosynthetic pathways in amenable production strains enables biotechnological access to a variety of valuable compounds by conversion of renewable resources. pseudomonas putida has emerged as a microbial laboratory work horse, with elaborated techniques for cultivation and genetic manipulation available. beyond that, this bacterium offers several particular advantages with regard to natural product biosynthesis, notably a versati ...201526099332
metcap: a bioinformatics probe design pipeline for large-scale targeted metagenomics.massive sequencing of genes from different environments has evolved metagenomics as central to enhancing the understanding of the wide diversity of micro-organisms and their roles in driving ecological processes. reduced cost and high throughput sequencing has made large-scale projects achievable to a wider group of researchers, though complete metagenome sequencing is still a daunting task in terms of sequencing as well as the downstream bioinformatics analyses. alternative approaches such as t ...201525880302
30s subunit-dependent activation of the sorangium cellulosum so ce56 aminoglycoside resistance-conferring 16s rrna methyltransferase kmr.methylation of bacterial 16s rrna within the ribosomal decoding center confers exceptionally high resistance to aminoglycoside antibiotics. this resistance mechanism is exploited by aminoglycoside producers for self-protection while functionally equivalent methyltransferases have been acquired by human and animal pathogenic bacteria. here, we report structural and functional analyses of the sorangium cellulosum so ce56 aminoglycoside resistance-conferring methyltransferase kmr. our results demon ...201525733511
amym, a novel maltohexaose-forming α-amylase from corallococcus sp. strain egb.a novel α-amylase, amym, was purified from the culture supernatant of corallococcus sp. strain egb. amym is a maltohexaose-forming exoamylase with an apparent molecular mass of 43 kda. based on the results of matrix-assisted laser desorption ionization-time of flight mass spectrometry and peptide mass fingerprinting of amym and by comparison to the genome sequence of corallococcus coralloides dsm 2259, the amym gene was identified and cloned into escherichia coli. amym encodes a secretory amylas ...201525576603
first genomic insights into members of a candidate bacterial phylum responsible for wastewater bulking.filamentous cells belonging to the candidate bacterial phylum ksb3 were previously identified as the causative agent of fatal filament overgrowth (bulking) in a high-rate industrial anaerobic wastewater treatment bioreactor. here, we obtained near complete genomes from two ksb3 populations in the bioreactor, including the dominant bulking filament, using differential coverage binning of metagenomic data. fluorescence in situ hybridization with 16s rrna-targeted probes specific for the two popula ...201525650158
the eukaryotic translation initiation regulator cdc123 defines a divergent clade of atp-grasp enzymes with a predicted role in novel protein modifications.deciphering the origin of uniquely eukaryotic features of sub-cellular systems, such as the translation apparatus, is critical in reconstructing eukaryogenesis. one such feature is the highly conserved, but poorly understood, eukaryotic protein cdc123, which regulates the abundance of the eukaryotic translation initiation eif2 complex and binds one of its components eif2γ. we show that the eukaryotic protein cdc123 defines a novel clade of atp-grasp enzymes distinguished from all other members o ...201525976611
bacterial sigma factors and anti-sigma factors: structure, function and distribution.sigma factors are multi-domain subunits of bacterial rna polymerase (rnap) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in rna synthesis. this review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (groups 2-4) that control a w ...201526131973
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
planctomycetes as novel source of bioactive molecules.marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. of particular importance are organisms like sponges and macroalgae and their associated microbiome. planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the actinobacteria. furthermore, genome mining revealed t ...201627570520
defined enzyme cocktail from the anaerobic fungus orpinomyces sp. strain c1a effectively releases sugars from pretreated corn stover and switchgrass.the anaerobic fungus orpinomyces strain c1a is capable of growth on various types of lignocellulosic substrates, and harbors an impressive reservoir of carbohydrate active enzymes (cazymes). using a minimum enzyme cocktail strategy, we constituted a four-component lignocellulolytic cocktail derived from highly transcribed c1a, and evaluated its efficacy against pretreated corn stover and switchgrass. hydrolysis yields ranged between 65-77.4%, depending on the lignocellulosic substrate and pretre ...201627381262
diversity of natural product biosynthetic genes in the microbiome of the deep sea sponges inflatella pellicula, poecillastra compressa, and stelletta normani.three different deep sea sponge species, inflatella pellicula, poecillastra compressa, and stelletta normani comprising seven individual samples, retrieved from depths of 760-2900 m below sea level, were investigated using 454 pyrosequencing for their secondary metabolomic potential targeting adenylation domain and ketosynthase domain sequences. the data obtained suggest a diverse microbial origin of nonribosomal peptide synthetases and polyketide synthase fragments that in part correlates with ...201627446062
phi class of glutathione s-transferase gene superfamily widely exists in nonplant taxonomic groups.glutathione s-transferases (gsts) constitute a superfamily of enzymes involved in detoxification of noxious compounds and protection against oxidative damage. gst class phi (gstf), one of the important classes of plant gsts, has long been considered as plant specific but was recently found in basidiomycete fungi. however, the range of nonplant taxonomic groups containing gstfs remains unknown. in this study, the distribution and phylogenetic relationships of nonplant gstfs were investigated. we ...201626884677
myxobacteria: moving, killing, feeding, and surviving together.myxococcus xanthus, like other myxobacteria, is a social bacterium that moves and feeds cooperatively in predatory groups. on surfaces, rod-shaped vegetative cells move in search of the prey in a coordinated manner, forming dynamic multicellular groups referred to as swarms. within the swarms, cells interact with one another and use two separate locomotion systems. adventurous motility, which drives the movement of individual cells, is associated with the secretion of slime that forms trails at ...201627303375
genome analysis of the fruiting body-forming myxobacterium chondromyces crocatus reveals high potential for natural product biosynthesis.here, we report the complete genome sequence of the type strain of the myxobacterial genus chondromyces, chondromyces crocatus cm c5. it presents one of the largest prokaryotic genomes featuring a single circular chromosome and no plasmids. analysis revealed an enlarged set of trna genes, along with reduced pressure on preferred codon usage compared to that of other bacterial genomes. the large coding capacity and the plethora of encoded secondary metabolite biosynthetic gene clusters are in lin ...201626773087
genetic engineering and heterologous expression of the disorazol biosynthetic gene cluster via red/et recombineering.disorazol, a macrocyclic polykitide produced by the myxobacterium sorangium cellulosum so ce12 and it is reported to have potential cytotoxic activity towards several cancer cell lines, including multi-drug resistant cells. the disorazol biosynthetic gene cluster (dis) from sorangium cellulosum (so ce12) was identified by transposon mutagenesis and cloned in a bacterial artificial chromosome (bac) library. the 58-kb dis core gene cluster was reconstituted from bacs via red/et recombineering and ...201626875499
antibiotics from predatory bacteria.bacteria, which prey on other microorganisms, are commonly found in the environment. while some of these organisms act as solitary hunters, others band together in large consortia before they attack their prey. anecdotal reports suggest that bacteria practicing such a wolfpack strategy utilize antibiotics as predatory weapons. consistent with this hypothesis, genome sequencing revealed that these micropredators possess impressive capacities for natural product biosynthesis. here, we will present ...201627340451
marine-derived myxobacteria of the suborder nannocystineae: an underexplored source of structurally intriguing and biologically active metabolites.myxobacteria are famous for their ability to produce most intriguing secondary metabolites. till recently, only terrestrial myxobacteria were in the focus of research. in this review, however, we discuss marine-derived myxobacteria, which are particularly interesting due to their relatively recent discovery and due to the fact that their very existence was called into question. the to-date-explored members of these halophilic or halotolerant myxobacteria are all grouped into the suborder nannocy ...201627340488
bacterial transcription as a target for antibacterial drug development.transcription, the first step of gene expression, is carried out by the enzyme rna polymerase (rnap) and is regulated through interaction with a series of protein transcription factors. rnap and its associated transcription factors are highly conserved across the bacterial domain and represent excellent targets for broad-spectrum antibacterial agent discovery. despite the numerous antibiotics on the market, there are only two series currently approved that target transcription. the determination ...201626764017
the complete genome sequence and analysis of a plasmid-bearing myxobacterial strain myxococcus fulvus 124b02 (m 206081).myxobacteria, phylogenetically located in the delta division of the proteobacteria, are well known for characterized social behaviors and large genomes of more than 9 mb in size. myxococcus fulvus is a typical species of the genus myxococcus in the family myxococcaceae. m. fulvus 124b02, originally isolated from a soil sample collected in northeast china, is the one and only presently known myxobacterial strain that harbors an endogenous autonomously replicating plasmid, named pmf1. the endogeno ...201626734118
comparison of myxobacterial diversity and evaluation of isolation success in two niches: kiritimati island and german compost.myxobacteria harbor an enormous potential for new bioactive secondary metabolites and therefore the isolation of in particular new groups is of great interest. the diversity of myxobacteria present in two ecological habitats, namely sand from kiritimati island and german compost, was evaluated by both cultivation-based and cultivation-independent methods. phylogenetic analyses of the strains in comparison with 16s rrna gene sequences from cultured and uncultured material in genbank revealed a gr ...201626669488
comparison of myxobacterial diversity and evaluation of isolation success in two niches: kiritimati island and german compost.myxobacteria harbor an enormous potential for new bioactive secondary metabolites and therefore the isolation of in particular new groups is of great interest. the diversity of myxobacteria present in two ecological habitats, namely sand from kiritimati island and german compost, was evaluated by both cultivation-based and cultivation-independent methods. phylogenetic analyses of the strains in comparison with 16s rrna gene sequences from cultured and uncultured material in genbank revealed a gr ...201626669488
heterologous production of the marine myxobacterial antibiotic haliangicin and its unnatural analogues generated by engineering of the biochemical pathway.despite their fastidious nature, marine myxobacteria have considerable genetic potential to produce novel secondary metabolites. the marine myxobacterium haliangium ochraceum smp-2 produces the antifungal polyketide haliangicin (1), but its productivity is unsatisfactory. the biosynthetic gene cluster hli (47.8 kbp) associated with 1 was identified and heterologously expressed in myxococcus xanthus to permit the production of 1 with high efficiency (tenfold greater amount and threefold faster in ...201626915413
microvirga massiliensis sp. nov., the human commensal with the largest genome.microvirga massiliensis sp. nov. strain jc119(t) is a bacteria isolated in marseille from a stool sample collected in senegal. the 16s rrna (jf824802) of m. massiliensis jc119(t) revealed 95% sequence identity with microvirga lotononidis wsm3557(t) (hm362432). this bacterium is aerobic, gram negative, catalase positive, and oxidase negative. the draft genome of m. massiliensis jc119(t) comprises a 9,207,211-bp-long genome that is the largest bacterial genome of an isolate in humans. the genome e ...201626749561
complete genome sequence and comparative genomics of a novel myxobacterium myxococcus hansupus.myxobacteria, a group of gram-negative aerobes, belong to the class δ-proteobacteria and order myxococcales. unlike anaerobic δ-proteobacteria, they exhibit several unusual physiogenomic properties like gliding motility, desiccation-resistant myxospores and large genomes with high coding density. here we report a 9.5 mbp complete genome of myxococcus hansupus that encodes 7,753 proteins. phylogenomic and genome-genome distance based analysis suggest that myxococcus hansupus is a novel member of ...201626900859
complete genome of the starch-degrading myxobacteria sandaracinus amylolyticus dsm 53668t.myxobacteria are members of δ-proteobacteria and are typified by large genomes, well-coordinated social behavior, gliding motility, and starvation-induced fruiting body formation. here, we report the 10.33 mb whole genome of a starch-degrading myxobacterium sandaracinus amylolyticus dsm 53668(t) that encodes 8,962 proteins, 56 trna, and two rrna operons. phylogenetic analysis, in silico dna-dna hybridization and average nucleotide identity reveal its divergence from other myxobacterial species a ...201627358428
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