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biosynthesis of polyketides in heterologous hosts.polyketide natural products show great promise as medicinal agents. typically the products of microbial secondary biosynthesis, polyketides are synthesized by an evolutionarily related but architecturally diverse family of multifunctional enzymes called polyketide synthases. a principal limitation for fundamental biochemical studies of these modular megasynthases, as well as for their applications in biotechnology, is the challenge associated with manipulating the natural microorganism that prod ...200111238987
characterization of benzoyl coenzyme a biosynthesis genes in the enterocin-producing bacterium "streptomyces maritimus".the novel benzoyl coenzyme a (benzoyl-coa) biosynthesis pathway in "streptomyces maritimus" was investigated through a series of target-directed mutations. genes involved in benzoyl-coa formation were disrupted through single-crossover homologous recombination, and the resulting mutants were analyzed for their ability to biosynthesize the benzoyl-coa-primed polyketide antibiotic enterocin. inactivation of the unique phenylalanine ammonia-lyase-encoding gene encp was previously shown to be absolu ...200312511484
recombinant environmental libraries provide access to microbial diversity for drug discovery from natural products.to further explore possible avenues for accessing microbial biodiversity for drug discovery from natural products, we constructed and screened a 5,000-clone "shotgun" environmental dna library by using an escherichia coli-streptomyces lividans shuttle cosmid vector and dna inserts from microbes derived directly (without cultivation) from soil. the library was analyzed by several means to assess diversity, genetic content, and expression of heterologous genes in both expression hosts. we found th ...200312513976
catabolism of arylboronic acids by arthrobacter nicotinovorans strain pba.arthrobacter sp. strain pba metabolized phenylboronic acid to phenol. the oxygen atom in phenol was shown to be derived from the atmosphere using (18)o(2). 1-naphthalene-, 2-naphthalene-, 3-cyanophenyl-, 2,5-fluorophenyl-, and 3-thiophene-boronic acids were also transformed to monooxygenated products. the oxygen atom in the product was bonded to the ring carbon atom originally bearing the boronic acid substituent with all the substrates tested.200312839810
a rhamnogalacturonan lyase in the clostridium cellulolyticum cellulosome.clostridium cellulolyticum secretes large multienzymatic complexes with plant cell wall-degrading activities named cellulosomes. most of the genes encoding cellulosomal components are located in a large gene cluster: cipc-cel48f-cel8c-cel9g-cel9e-orfx-cel9h-cel9j-man5k-cel9m. downstream of the cel9m gene, a new open reading frame was discovered and named rgl11y. amino acid sequence analysis indicates that this gene encodes a multidomain pectinase, rgl11y, containing an n-terminal signal sequence ...200312896991
development of a mariner-based transposon for use in sorangium cellulosum.in order to generate marked insertions in the myxobacterium sorangium cellulosum, a transposon based on the eukaryotic mariner transposon was developed. the transposition frequency was increased with the use of a mutated tnp gene. the transposon randomly inserts into the chromosome, as demonstrated by targeted mutagenesis of the epok gene.200314532095
subtractive hybridization reveals a type i polyketide synthase locus specific to mycobacterium ulcerans.mycobacterium ulcerans causes buruli ulcer, the third most prevalent mycobacterial infection of immunocompetent humans after tuberculosis and leprosy. recent work has shown that the production by m. ulcerans of mycolactone, a novel polyketide, may partly explain the pathogenesis of buruli ulcer. to search for the genetic basis of virulence in m. ulcerans, we took advantage of the close genetic relationship between m. ulcerans and mycobacterium marinum by performing genomic suppressive subtractiv ...200314617651
genetics of zwittermicin a production by bacillus cereus.zwittermicin a represents a new chemical class of antibiotic and has diverse biological activities, including suppression of oomycete diseases of plants and potentiation of the insecticidal activity of bacillus thuringiensis. to identify genes involved in zwittermicin a production, we generated 4,800 transposon mutants of b. cereus uw101c and screened them for zwittermicin a accumulation. nine mutants did not produce detectable zwittermicin a, and one mutant produced eightfold more than the pare ...200414711631
the opportunistic pathogen pseudomonas aeruginosa carries a secretable arachidonate 15-lipoxygenase.in mammals, lipoxygenases play key roles in inflammation by initiating the transformation of arachidonic acid into potent bioactive lipid mediators such as leukotrienes and lipoxins. in general, most bacteria are believed to lack lipoxygenases and their polyunsaturated fatty acid substrates. it is therefore of interest that an orf (pa1169) with high homology to eukaryotic lipoxygenases was discovered by analysis of the whole-genome sequence of the opportunistic bacterial pathogen pseudomonas aer ...200414766977
novel genes that influence development in streptomyces coelicolor.filamentous soil bacteria of the genus streptomyces carry out complex developmental cycles that result in sporulation and production of numerous secondary metabolites with pharmaceutically important activities. to further characterize the molecular basis of these developmental events, we screened for mutants of streptomyces coelicolor that exhibit aberrant morphological differentiation and/or secondary metabolite production. on the basis of this screening analysis and the subsequent complementat ...200415150245
genome organization and localization of the puflm genes of the photosynthesis reaction center in phylogenetically diverse marine alphaproteobacteria.genome organization, plasmid content and localization of the puflm genes of the photosynthesis reaction center were studied by pulsed-field gel electrophoresis (pfge) in marine phototrophic alphaproteobacteria. both anaerobic phototrophs (rhodobacter veldkampii and rhodobacter sphaeroides) and strictly aerobic anoxygenic phototrophs from the roseobacter-sulfitobacter-silicibacter clade (roseivivax halodurans, roseobacter litoralis, staleya guttiformis, roseovarius tolerans, and five new strains ...200415184132
cloning, sequencing, and functional analysis of an iterative type i polyketide synthase gene cluster for biosynthesis of the antitumor chlorinated polyenone neocarzilin in "streptomyces carzinostaticus".neocarzilins (nczs) are antitumor chlorinated polyenones produced by "streptomyces carzinostaticus" var. f-41. the gene cluster responsible for the biosynthesis of nczs was cloned and characterized. dna sequence analysis of a 33-kb region revealed a cluster of 14 open reading frames (orfs), three of which (orf4, orf5, and orf6) encode type i polyketide synthase (pks), which consists of four modules. unusual features of the modular organization is the lack of an obvious acyltransferase domain on ...200415328113
biochemical characterization of a prokaryotic phenylalanine ammonia lyase.the committed biosynthetic reaction to benzoyl-coenzyme a in the marine bacterium "streptomyces maritimus" is carried out by the novel prokaryotic phenylalanine ammonia lyase (pal) encp, which converts the primary amino acid l-phenylalanine to trans-cinnamic acid. recombinant encp is specific for l-phenylalanine and shares many biochemical features with eukaryotic pals, which are substantially larger proteins by approximately 200 amino acid residues.200515937191
distribution and diversity of natural product genes in marine and freshwater cyanobacterial cultures and genomes.natural products are a functionally diverse class of biochemically synthesized compounds, which include antibiotics, toxins, and siderophores. in this paper, we describe both the detection of natural product activities and the sequence identification of gene fragments from two molecular systems that have previously been implicated in natural product production, i.e., nonribosomal peptide synthetases (nrpss) and modular polyketide synthases (pkss), in diverse marine and freshwater cyanobacterial ...200516269782
biological evaluation of tubulysin a: a potential anticancer and antiangiogenic natural product.tubulysin a (tuba) is a natural product isolated from a strain of myxobacteria that has been shown to depolymerize microtubules and induce mitotic arrest. the potential of tuba as an anticancer and antiangiogenic agent is explored in the present study. tuba shows potent antiproliferative activity in a panel of human cancer cell lines irrespective of their multidrug resistance properties. it induces apoptosis in cancer cells but not in normal cells and shows significant potential antiangiogenic p ...200616489930
yersiniabactin production by pseudomonas syringae and escherichia coli, and description of a second yersiniabactin locus evolutionary group.the siderophore and virulence factor yersiniabactin is produced by pseudomonas syringae. yersiniabactin was originally detected by high-pressure liquid chromatography (hplc); commonly used pcr tests proved ineffective. yersiniabactin production in p. syringae correlated with the possession of irp1 located in a predicted yersiniabactin locus. three similarly divergent yersiniabactin locus groups were determined: the yersinia pestis group, the p. syringae group, and the photorhabdus luminescens gr ...200616751485
reconstitution of the myxothiazol biosynthetic gene cluster by red/et recombination and heterologous expression in myxococcus xanthus.although many secondary metabolites exhibiting important pharmaceutical and agrochemical activities have been isolated from myxobacteria, most of these microorganisms remain difficult to handle genetically. to utilize their metabolic potential, heterologous expression methodologies are currently being developed. here, the red/et recombination technology was used to perform all required gene cluster engineering steps in escherichia coli prior to the transfer into the chromosome of the heterologou ...200616997979
efficacy of ambruticin analogs in a murine model of invasive pulmonary aspergillosis.ambruticins are a family of polyketides. the antifungal activity of an ambruticin, kosn-2079, was tested in the mouse model of invasive aspergillosis. kosn-2079 significantly reduced pulmonary fungal burdens and improved survival over that with the vehicle control. these results support the continued development of ambruticins as antifungal agents.200617005833
incorporation of nonmethyl branches by isoprenoid-like logic: multiple beta-alkylation events in the biosynthesis of myxovirescin a1.several polyketide secondary metabolites are predicted to undergo isoprenoid-like beta-alkylations during biosynthesis. one such secondary metabolite is myxovirescin a1, produced by myxococcus xanthus. myxovirescin is of special interest in that it appears to undergo two distinct beta-alkylations. additionally, the myxovirescin biosynthetic gene cluster lacks tandem thiolation domains required in the synthesis of other beta-branched secondary metabolites. to probe the origins of the beta-branche ...200717656320
social bacteria and asocial eukaryotes. 200818199122
transfer of the high-gc cyclohexane carboxylate degradation pathway from rhodopseudomonas palustris to escherichia coli for production of biotin.this work demonstrates the transfer of the five-gene cyclohexane carboxylate (chc) degradation pathway from the high-gc alphaproteobacterium rhodopseudomonas palustris to escherichia coli, a gammaproteobacterium. the degradation product of this pathway is pimeloyl-coa, a key metabolite in e. coli's biotin biosynthetic pathway. this pathway is useful for biotin overproduction in e. coli; however, the expression of gc-rich genes is troublesome in this host. when the native r. palustris chc degrada ...200818396082
the mosaic genome of anaeromyxobacter dehalogenans strain 2cp-c suggests an aerobic common ancestor to the delta-proteobacteria.anaeromyxobacter dehalogenans strain 2cp-c is a versaphilic delta-proteobacterium distributed throughout many diverse soil and sediment environments. 16s rrna gene phylogenetic analysis groups a. dehalogenans together with the myxobacteria, which have distinguishing characteristics including strictly aerobic metabolism, sporulation, fruiting body formation, and surface motility. analysis of the 5.01 mb strain 2cp-c genome substantiated that this organism is a myxobacterium but shares genotypic t ...200818461135
eukaryotic-like protein kinases in the prokaryotes and the myxobacterial kinome.ser/thr/tyr kinases, which together comprise a major class of regulatory proteins in eukaryotes, were not believed to play an important role in prokaryotes until recently. however, our analysis of 626 prokaryotic genomes reveals that eukaryotic-like protein kinases (elks) are found in nearly two-thirds of the sequenced strains. we have identified 2697 elks, most of which are encoded by multicellular strains of the phyla proteobacteria (myxococcales), actinobacteria, cyanobacteria, and chloroflex ...200818836084
the rna polymerase "switch region" is a target for inhibitors.the alpha-pyrone antibiotic myxopyronin (myx) inhibits bacterial rna polymerase (rnap). here, through a combination of genetic, biochemical, and structural approaches, we show that myx interacts with the rnap "switch region"--the hinge that mediates opening and closing of the rnap active center cleft--to prevent interaction of rnap with promoter dna. we define the contacts between myx and rnap and the effects of myx on rnap conformation and propose that myx functions by interfering with opening ...200818957204
interrogating the bioactive pharmacophore of the latrunculin chemotype by investigating the metabolites of two taxonomically unrelated sponges.this study involved a campaign to isolate and study additional latrunculin analogues from two taxonomically unrelated sponges, cacospongia mycofijiensis and negombata magnifica. a total of 13 latrunculin analogues were obtained by four different ways, reisolation (1-4), our repository (5, 6), new derivatives (7-12), and a synthetic analogue (7a). the structures of the new metabolites were elucidated on the basis of a combination of comprehensive 1d and 2d nmr analysis, application of dft calcula ...200818942825
therapeutic effect against human xenograft tumors in nude mice by the third generation microtubule stabilizing epothilones.the epothilones represent a promising class of natural product-based antitumor drug candidates. although these compounds operate through a microtubule stabilization mechanism similar to that of taxol, the epothilones offer a major potential therapeutic advantage in that they retain their activity against multidrug-resistant cell lines. we have been systematically synthesizing and evaluating synthetic epothilone congeners that are not accessible through modification of the natural product itself. ...200818755900
in vivo and in vitro trans-acylation by bryp, the putative bryostatin pathway acyltransferase derived from an uncultured marine symbiont.the putative modular polyketide synthase (pks) that prescribes biosynthesis of the bryostatin natural products from the uncultured bacterial symbiont of the marine bryozoan bugula neritina possesses a discrete open reading frame (orf) (bryp) that encodes a protein containing tandem acyltransferase (at) domains upstream of the pks orfs. bryp is hypothesized to catalyze in trans acylation of the pks modules for polyketide chain elongation. to verify conservation of function, bryp was introduced in ...200819022178
analysis of the cryptophycin p450 epoxidase reveals substrate tolerance and cooperativity.cryptophycins are potent anticancer agents isolated from nostoc sp. atcc 53789 and nostoc sp. gsv 224. the most potent natural cryptophycin analogues retain a beta-epoxide at the c2'-c3' position of the molecule. a p450 epoxidase encoded by c rpe recently identified from the cryptophycin gene cluster was shown to install this key functional group into cryptophycin-4 (cr-4) to produce cryptophycin-2 (cr-2) in a regio- and stereospecific manner. here we report a detailed characterization of the cr ...200818366166
bioinformatics and experimental analysis of proteins of two-component systems in myxococcus xanthus.proteins of two-component systems (tcs) have essential functions in the sensing of external and self-generated signals in bacteria and in the generation of appropriate output responses. accordingly, in myxococcus xanthus, tcs are important for normal motility and fruiting body formation and sporulation. here we analyzed the m. xanthus genome for the presence and genetic organization of genes encoding tcs. two hundred seventy-two tcs genes were identified, 251 of which are not part of che gene cl ...200817993514
bioinformatics and experimental analysis of proteins of two-component systems in myxococcus xanthus.proteins of two-component systems (tcs) have essential functions in the sensing of external and self-generated signals in bacteria and in the generation of appropriate output responses. accordingly, in myxococcus xanthus, tcs are important for normal motility and fruiting body formation and sporulation. here we analyzed the m. xanthus genome for the presence and genetic organization of genes encoding tcs. two hundred seventy-two tcs genes were identified, 251 of which are not part of che gene cl ...200817993514
human mass balance study of the novel anticancer agent ixabepilone using accelerator mass spectrometry.ixabepilone (bms-247550) is a semi-synthetic, microtubule stabilizing epothilone b analogue which is more potent than taxanes and has displayed activity in taxane-resistant patients. the human plasma pharmacokinetics of ixabepilone have been described. however, the excretory pathways and contribution of metabolism to ixabepilone elimination have not been determined. to investigate the elimination pathways of ixabepilone we initiated a mass balance study in cancer patients. due to autoradiolysis, ...200717347871
novel expression hosts for complex secondary metabolite megasynthetases: production of myxochromide in the thermopilic isolate corallococcus macrosporus gt-2.abstract: although many secondary metabolites with diverse biological activities have been isolated from myxobacteria, most strains of these biotechnologically important gliding prokaryotes remain difficult to handle genetically. in this study we describe the new fast growing myxobacterial thermophilic isolate gt-2 as a heterologous host for the expression of natural product biosynthetic pathways isolated from other myxobacteria. according to the results of sequence analysis of the 16s rdna, thi ...200919126236
structural determinants and modulation of substrate specificity in phenylalanine-tyrosine ammonia-lyases.aromatic amino acid ammonia-lyases catalyze the deamination of l-his, l-phe, and l-tyr, yielding ammonia plus aryl acids bearing an alpha,beta-unsaturated propenoic acid. we report crystallographic analyses of unliganded rhodobacter sphaeroides tyrosine ammonia-lyase (rstal) and rstal bound to p-coumarate and caffeate. his 89 of rstal forms a hydrogen bond with the p-hydroxyl moieties of coumarate and caffeate. his 89 is conserved in tals but replaced in phenylalanine ammonia-lyases (pals) and h ...200617185228
formation and metabolism of methylmalonyl coenzyme a in corynebacterium glutamicum.genome sequence information suggests that b(12)-dependent mutases are present in a number of bacteria, including members of the suborder corynebacterineae like mycobacterium tuberculosis and corynebacterium glutamicum. we here functionally identify a methylmalonyl coenzyme a (coa) mutase in c. glutamicum that is retained in all of the members of the suborder corynebacterineae and is encoded by ncgl1471, ncgl1472, and ncgl1470. in addition, we observe the presence of methylmalonate in c. glutamic ...200919233926
the structural basis for substrate anchoring, active site selectivity, and product formation by p450 pikc from streptomyces venezuelae.the pikromycin (pik)/methymycin biosynthetic pathway of streptomyces venezuelae represents a valuable system for dissecting the fundamental mechanisms of modular polyketide biosynthesis, aminodeoxysugar assembly, glycosyltransfer, and hydroxylation leading to the production of a series of macrolide antibiotics, including the natural ketolides narbomycin and pikromycin. in this study, we describe four x-ray crystal structures and allied functional studies for pikc, the remarkable p450 monooxygena ...200616825192
molecular identification of a novel deltaproteobacterium as the etiologic agent of epizootic bovine abortion (foothill abortion).epizootic bovine abortion (eba) is endemic in california's coastal range and the foothill regions of the sierra nevada, where it has been the primary diagnosed cause of abortion in beef cattle for >50 years. investigation of these losses has defined a specific fetal syndrome characterized by late-term abortion or birth of weak or dead calves. although the unusual clinical presentation and unique fetal pathology associated with eba have been recognized since the 1950s, the identity of the etiolog ...200515695652
measure of synonymous codon usage diversity among genes in bacteria.in many bacteria, intragenomic diversity in synonymous codon usage among genes has been reported. however, no quantitative attempt has been made to compare the diversity levels among different genomes. here, we introduce a mean dissimilarity-based index (dmean) for quantifying the level of diversity in synonymous codon usage among all genes within a genome.200919480720
isolation and characterization of novel marine-derived actinomycete taxa rich in bioactive metabolites.a unique selective enrichment procedure has resulted in the isolation and identification of two new genera of marine-derived actinobacteria. approximately 90% of the microorganisms cultured by using the presented method were from the prospective new genera, a result indicative of its high selectivity. in this study, 102 actinomycetes were isolated from subtidal marine sediments collected from the bismarck sea and the solomon sea off the coast of papua new guinea. a combination of physiological p ...200415574955
genome mining in sorangium cellulosum so ce56: identification and characterization of the homologous electron transfer proteins of a myxobacterial cytochrome p450.myxobacteria, especially members of the genus sorangium, are known for their biotechnological potential as producers of pharmaceutically valuable secondary metabolites. the biosynthesis of several of those myxobacterial compounds includes cytochrome p450 activity. although class i cytochrome p450 enzymes occur wide-spread in bacteria and rely on ferredoxins and ferredoxin reductases as essential electron mediators, the study of these proteins is often neglected. therefore, we decided to search i ...200919696019
myxococcus xanthus pph2 is a manganese-dependent protein phosphatase involved in energy metabolism.the multicellular behavior of the myxobacterium myxococcus xanthus requires the participation of an elevated number of signal-transduction mechanisms to coordinate the cell movements and the sequential changes in gene expression patterns that lead to the morphogenetic and differentiation events. these signal-transduction mechanisms are mainly based on two-component systems and on the reversible phosphorylation of protein targets mediated by eukaryotic-like protein kinases and phosphatases. among ...200919706604
characterization of the polyene macrolide p450 epoxidase from streptomyces natalensis that converts de-epoxypimaricin into pimaricin.the biosynthesis of the antifungal agent pimaricin by streptomyces natalensis has been proposed to involve a cytochrome p450 encoded by the gene pimd. pimaricin is derived from its immediate precursor de-epoxypimaricin by epoxidation of the c-4-c-5 double bond on the macrolactone ring. we have overproduced pimd with a n-terminal his6 affinity tag in escherichia coli and purified the enzyme for kinetic analysis. the protein showed a reduced co-difference spectrum with a soret maximum at 450 nm, i ...200515228385
tonb-dependent transporters and their occurrence in cyanobacteria.different iron transport systems evolved in gram-negative bacteria during evolution. most of the transport systems depend on outer membrane localized tonb-dependent transporters (tbdts), a periplasma-facing tonb protein and a plasma membrane localized machinery (exbbd). so far, iron chelators (siderophores), oligosaccharides and polypeptides have been identified as substrates of tbdts. for iron transport, three uptake systems are defined: the lactoferrin/transferrin binding proteins, the porphyr ...200919821963
tertiary structure and characterization of a glycoside hydrolase family 44 endoglucanase from clostridium acetobutylicum.a gene encoding a glycoside hydrolase family 44 (gh44) protein from clostridium acetobutylicum atcc 824 was synthesized and transformed into escherichia coli. the previously uncharacterized protein was expressed with a c-terminal his tag and purified by nickel-nitrilotriacetic acid affinity chromatography. crystallization and x-ray diffraction to a 2.2-a resolution revealed a triose phosphate isomerase (tim) barrel-like structure with additional greek key and beta-sandwich folds, similar to othe ...201019915043
tertiary structure and characterization of a glycoside hydrolase family 44 endoglucanase from clostridium acetobutylicum.a gene encoding a glycoside hydrolase family 44 (gh44) protein from clostridium acetobutylicum atcc 824 was synthesized and transformed into escherichia coli. the previously uncharacterized protein was expressed with a c-terminal his tag and purified by nickel-nitrilotriacetic acid affinity chromatography. crystallization and x-ray diffraction to a 2.2-a resolution revealed a triose phosphate isomerase (tim) barrel-like structure with additional greek key and beta-sandwich folds, similar to othe ...201019915043
management of advanced breast cancer with the epothilone b analog, ixabepilone.despite the activity of standard chemotherapies in advanced breast cancer, disease progression remains inevitable. most patients exposed to anthracyclines and taxanes develop resistance and a significant subset shows primary resistance. the increasing use of these agents as adjuvant therapy may result in more anthracycline- and taxane-resistant patients in the metastatic setting; few treatment options are available for patients with metastatic breast cancer (mbc) resistant to multiple chemothera ...200919920932
genes coding for hepatotoxic heptapeptides (microcystins) in the cyanobacterium anabaena strain 90.the cluster of microcystin synthetase genes from anabaena strain 90 was sequenced and characterized. the total size of the region is 55.4 kb, and the genes are organized in three putative operons. the first operon (mcya-mcyb-mcyc) is transcribed in the opposite direction from the second operon (mcyg-mcyd-mcyj-mcye-mcyf-mcyi) and the third operon (mcyh). the genes mcya, mcyb, and mcyc encode nonribosomal peptide synthetases (nrps), while mcyd codes for a polyketide synthase (pks), and mcyg and mc ...200414766543
availability of specific reductases controls the temporal activity of the cytochrome p450 complement of streptomyces coelicolor a3(2).the annotated genome of streptomyces coelicolor a3(2) revealed 18 cytosolic cytochromes p450 (cyps) with six ferredoxin (fdx) proteins and two soluble ferredoxin reductases (fpr), their putative electron transport proteins. mrna expression was observed for all 18 cyps throughout growth and secondary metabolism, from 3 h after spore germination, and all cyp proteins examined also were present. expression of members of the fdx complement was detected from the same time point, yet both fpr were det ...200414704268
the stigmatella aurantiaca homolog of myxococcus xanthus high-mobility-group a-type transcription factor card: insights into the functional modules of card and their distribution in bacteria.transcriptional factor card is the only reported prokaryotic analog of eukaryotic high-mobility-group a (hmga) proteins, in that it has contiguous acidic and at hook dna-binding segments and multifunctional roles in myxococcus xanthus carotenogenesis and fruiting body formation. hmga proteins are small, randomly structured, nonhistone, nuclear architectural factors that remodel dna and chromatin structure. here we report on a second at hook protein, card(sa), that is very similar to card and tha ...200312775690
heterologous expression of epothilone biosynthetic genes in myxococcus xanthus.epothilones are potential anticancer drugs that stabilize microtubules in a manner similar to paclitaxel (taxol). epothilones are produced from the myxobacterium sorangium cellulosum, which has a 16-h doubling time and produces only milligram-per-liter amounts of epothilone a and epothilone b. furthermore, genetic manipulation of s. cellulosum is difficult. to produce epothilones in a more genetically amenable and rapidly growing host, we chose the closely related and best-characterized myxobact ...200212183227
characterization and description of anaeromyxobacter dehalogenans gen. nov., sp. nov., an aryl-halorespiring facultative anaerobic myxobacterium.five strains were isolated which form a physiologically and phylogenetically coherent group of chlororespiring microorganisms and represent the first taxon in the myxobacteria capable of anaerobic growth. the strains were enriched and isolated from various soils and sediments based on their ability to grow using acetate as an electron donor and 2-chlorophenol (2-cph) as an electron acceptor. they are slender gram-negative rods with a bright red pigmentation that exhibit gliding motility and form ...200211823233
characterization of indigoidine biosynthetic genes in erwinia chrysanthemi and role of this blue pigment in pathogenicity.in the plant-pathogenic bacterium erwinia chrysanthemi production of pectate lyases, the main virulence determinant, is modulated by a complex network involving several regulatory proteins. one of these regulators, pecs, also controls the synthesis of a blue pigment identified as indigoidine. since production of this pigment is cryptic in the wild-type strain, e. chrysanthemi ind mutants deficient in indigoidine synthesis were isolated by screening a library of tn5-b21 insertions in a pecs mutan ...200211790734
cdnl, a member of the large card-like family of bacterial proteins, is vital for myxococcus xanthus and differs functionally from the global transcriptional regulator card.card, a global transcriptional regulator in myxococcus xanthus, interacts with carg via cardnter, its n-terminal domain, and with dna via a eukaryotic hmga-type c-terminal domain. genomic analysis reveals a large number of standalone proteins resembling cardnter. these constitute, together with the rna polymerase (rnap) interacting domain, rid, of transcription-repair coupling factors, the card_trcf protein family. we show that one such cardnter-like protein, m. xanthus cdnl, cannot functionally ...201020371514
in vitro reconstitution of the myxochelin biosynthetic machinery of stigmatella aurantiaca sg a15: biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases.microorganisms produce iron-chelating compounds to sequester the iron essential for growth from the environment. many of these compounds are biosynthesized by nonribosomal peptide synthetases, some in cooperation with polyketide synthases. myxochelins are produced by the myxobacterium stigmatella aurantiaca sg a15, and the corresponding gene cluster was cloned recently. we have undertaken to express heterologously the myxochelin biosynthetic machinery in escherichia coli. to activate the involve ...200111562468
identification of diverse antimicrobial resistance determinants carried on bacterial, plasmid, or viral metagenomes from an activated sludge microbial assemblage.using both sequence- and function-based metagenomic approaches, multiple antibiotic resistance determinants were identified within metagenomic libraries constructed from dna extracted from bacterial chromosomes, plasmids, or viruses within an activated sludge microbial assemblage. metagenomic clones and a plasmid that in escherichia coli expressed resistance to chloramphenicol, ampicillin, or kanamycin were isolated, with many cloned dna sequences lacking any significant homology to known antibi ...201020382816
phenolic acids act as signaling molecules in plant-microbe symbioses.phenolic acids are the main polyphenols made by plants. these compounds have diverse functions and are immensely important in plant-microbe interactions/symbiosis. phenolic compounds act as signaling molecules in the initiation of legumerhizobia symbioses, establishment of arbuscular mycorrhizal symbioses and can act as agents in plant defense. flavonoids are a diverse class of polyphenolic compounds that have received considerable attention as signaling molecules involved in plant-microbe inter ...201020400851
oxazolomycin biosynthesis in streptomyces albus ja3453 featuring an "acyltransferase-less" type i polyketide synthase that incorporates two distinct extender units.the oxazolomycins (ozms) are a growing family of antibiotics produced by several streptomyces species that show diverse and important antibacterial, antitumor, and anti-human immunodeficiency virus activity. oxazolomycin a is a peptide-polyketide hybrid compound containing a unique spiro-linked beta-lactone/gamma-lactam, a 5-substituted oxazole ring. the oxazolomycin biosynthetic gene cluster (ozm) was identified from streptomyces albus ja3453 and localized to 79.5-kb dna, consisting of 20 open ...201020406823
the synthesis, discovery, and development of a highly promising class of microtubule stabilization agents: curative effects of desoxyepothilones b and f against human tumor xenografts in nude mice.we have evaluated two synthetic epothilone analogues lacking the 12,13-epoxide functionality, 12,13-desoxyepothilone b (depob), and 12,13-desoxyepothilone f (depof). the concentrations required for 50% growth inhibition (ic(50)) for a variety of anticancer agents were measured in ccrf-cem/vbl1000 cells (2,048-fold resistance to vinblastine). by using depob, depof, aza-epob, and paclitaxel, the ic(50) values were 0.029, 0.092, 2.99, and 5.17 microm, respectively. these values represent 4-, 33.5-, ...200111438750
mutations that confer resistance to 2-deoxyglucose reduce the specific activity of hexokinase from myxococcus xanthus.the glucose analog 2-deoxyglucose (2dglc) inhibits the growth and multicellular development of myxococcus xanthus. mutants of m. xanthus resistant to 2dglc, designated hex mutants, arise at a low spontaneous frequency. expression of the escherichia coli glk (glucokinase) gene in m. xanthus hex mutants restores 2dglc sensitivity, suggesting that these mutants arise upon the loss of a soluble hexokinase function that phosphorylates 2dglc to form the toxic intermediate, 2-deoxyglucose-6-phosphate. ...199910094702
desoxyepothilone b: an efficacious microtubule-targeted antitumor agent with a promising in vivo profile relative to epothilone b.a new class of 16-membered macrolides, the epothilones (epos), has been synthesized and evaluated for antitumor potential in vitro and in vivo. recent studies in these and other laboratories showed that epothilones and paclitaxel (paclitaxel) share similar mechanisms of action in stabilizing microtubule arrays as indicated by binding-displacement studies, substitution for paclitaxel in paclitaxel-dependent cell growth, and electron microscopic examinations. the present study examined cell growth ...19989689134
a sorangium cellulosum (myxobacterium) gene cluster for the biosynthesis of the macrolide antibiotic soraphen a: cloning, characterization, and homology to polyketide synthase genes from actinomycetes.a 40-kb region of dna from sorangium cellulosum so ce26, which contains polyketide synthase (pks) genes for synthesis of the antifungal macrolide antibiotic soraphen a, was cloned. these genes were detected by homology to streptomyces violaceoruber genes encoding components of granaticin pks, thus extending this powerful technique for the identification of bacterial pks genes, which has so far been applied only to actinomycetes, to the gram-negative myxobacteria. functional analysis by gene disr ...19957601830
the group iii two-component histidine kinase of filamentous fungi is involved in the fungicidal activity of the bacterial polyketide ambruticin.we have shown that the plant pathogen alternaria brassicicola exhibited very high susceptibility to ambruticin vs4 and to a lesser extent to the phenylpyrrole fungicide fludioxonil. these compounds are both derived from natural bacterial metabolites with antifungal properties and are thought to exert their toxicity by interfering with osmoregulation in filamentous fungi. disruption of the osmosensor group iii histidine kinase gene abnik1 (for a. brassicola nik1) resulted in high levels of resist ...200919011080
the group iii two-component histidine kinase of filamentous fungi is involved in the fungicidal activity of the bacterial polyketide ambruticin.we have shown that the plant pathogen alternaria brassicicola exhibited very high susceptibility to ambruticin vs4 and to a lesser extent to the phenylpyrrole fungicide fludioxonil. these compounds are both derived from natural bacterial metabolites with antifungal properties and are thought to exert their toxicity by interfering with osmoregulation in filamentous fungi. disruption of the osmosensor group iii histidine kinase gene abnik1 (for a. brassicola nik1) resulted in high levels of resist ...200919011080
efficient transfer of two large secondary metabolite pathway gene clusters into heterologous hosts by transposition.horizontal gene transfer by transposition has been widely used for transgenesis in prokaryotes. however, conjugation has been preferred for transfer of large transgenes, despite greater restrictions of host range. we examine the possibility that transposons can be used to deliver large transgenes to heterologous hosts. this possibility is particularly relevant to the expression of large secondary metabolite gene clusters in various heterologous hosts. recently, we showed that the engineering of ...200818701643
damage of streptococcus mutans biofilms by carolacton, a secondary metabolite from the myxobacterium sorangium cellulosum.streptococcus mutans is a major pathogen in human dental caries. one of its important virulence properties is the ability to form biofilms (dental plaque) on tooth surfaces. eradication of such biofilms is extremely difficult. we therefore screened a library of secondary metabolites from myxobacteria for their ability to damage biofilms of s. mutans.201020659313
origins of replication in sorangium cellulosum and microcystis aeruginosa.the genome of sorangium cellulosum has recently been completely sequenced, and it is the largest bacterial genome sequenced so far. in their report, schneiker et al. (in complete genome sequence of the myxobacterium sorangium cellulosum, nat. biotechnol., 2007, 25, 1281-1289) concluded that 'in the absence of the gc-skew inversion typically seen at the replication origin of bacterial chromosomes, it was not possible to discern the location of oric'. in addition, the complete genome of microcysti ...200818477575
development of an environmental functional gene microarray for soil microbial communities.functional attributes of microbial communities are difficult to study, and most current techniques rely on dna- and rrna-based profiling of taxa and genes, including microarrays containing sequences of known microorganisms. to quantify gene expression in environmental samples in a culture-independent manner, we constructed an environmental functional gene microarray (e-fga) consisting of 13,056 mrna-enriched anonymous microbial clones from diverse microbial communities to profile microbial gene ...201020851978
inactivation of the ketoreductase gilu gene of the gilvocarcin biosynthetic gene cluster yields new analogues with partly improved biological activity.four new analogues of the gilvocarcin-type aryl-c-glycoside antitumor compounds, namely 4'-hydroxy gilvocarcin v (4'-oh-gv), 4'-hydroxy gilvocarcin m, 4'-hydroxy gilvocarcin e and 12-demethyl-defucogilvocarcin v, were produced through inactivation of the gilu gene. the 4'-oh-analogues showed improved activity against lung cancer cell lines as compared to their parent compounds without 4'-oh group (gilvocarcins v and e). the structures of the sugar-containing new mutant products indicate that the ...200919067453
isolation, biology and chemistry of the disorazoles: new anti-cancer macrodiolides.covering: 1994 to 2008. the disorazoles comprise a family of 29 closely related macrocyclic polyketides isolated in 1994 from the fermentation broth of the gliding myxobacterium sorangium cellulosum. disorazoles a1, e and c1 have shown exceptional biological activites toward inhibiting the proliferation of human cancer cell lines in picomolar and nanomolar concentrations through the disruption of microtubule polymerization. this review gives a brief introduction describing the biosynthesis and t ...200919387496
marine myxobacteria as a source of antibiotics--comparison of physiology, polyketide-type genes and antibiotic production of three new isolates of enhygromyxa salina.three myxobacterial strains, designated swb004, swb005 and swb006, were obtained from beach sand samples from the pacific ocean and the north sea. the strains were cultivated in salt water containing media and subjected to studies to determine their taxonomic status, the presence of genes for the biosynthesis of polyketides and antibiotic production. 16s rdna sequence analysis revealed the type strain enhygromyxa salina shk-1(t) as their closest homolog, displaying between 98% (swb005) and 99% ( ...201020948900
effects of site-directed mutagenesis of mgla on motility and swarming of myxococcus xanthus.the mgla gene from the bacterium myxococcus xanthus encodes a 22kda protein related to the ras superfamily of monomeric gtpases. mgla is required for the normal function of a-motility (adventurous), s-motility (social), fruiting body morphogenesis, and sporulation. mgla and its homologs differ from all eukaryotic and other prokaryotic gtpases because they have a threonine (thr78) in place of the highly conserved aspartate residue of the consensus pm3 (phosphate-magnesium binding) region. to iden ...201021083931
evolution of bacterial phosphoglycerate mutases: non-homologous isofunctional enzymes undergoing gene losses, gains and lateral transfers.the glycolytic phosphoglycerate mutases exist as non-homologous isofunctional enzymes (nise) having independent evolutionary origins and no similarity in primary sequence, 3d structure, or catalytic mechanism. cofactor-dependent pgm (dpgm) requires 2,3-bisphosphoglycerate for activity; cofactor-independent pgm (ipgm) does not. the pgm profile of any given bacterium is unpredictable and some organisms such as escherichia coli encode both forms.201021187861
design, synthesis and biological evaluation of bridged epothilone d analogues.six epothilone d analogues with a bridge between the c4-methyl and the c12-methyl carbons were prepared in an attempt to constrain epothilone d to its proposed tubulin-binding conformation. ring-closing metathesis (rcm) was employed as the key step to build the c4-c26 bridge. in antiproliferative assays in the human ovarian cancer (a2780) and prostate cancer (pc3) cell lines, and also in tubulin assembly assay, all these compounds proved to be less active than epothilone d.200819039362
microtubule binding and disruption and induction of premature senescence by disorazole c(1).disorazoles comprise a family of 29 macrocyclic polyketides isolated from the fermentation broth of the myxobacterium sorangium cellulosum. the major fermentation product, disorazole a(1), was found previously to irreversibly bind to tubulin and to have potent cytotoxic activity against tumor cells, possibly because of its highly electrophilic epoxide moiety. to test this hypothesis, we synthesized the epoxide-free disorazole c(1) and found it retained potent antiproliferative activity against t ...200919066338
fatty acid-related phylogeny of myxobacteria as an approach to discover polyunsaturated omega-3/6 fatty acids.in an analysis of 47 aerobic myxobacterial strains, representing 19 genera in suborders cystobacterineae, nannocystineae, sorangiineae, and a novel isolate, "aetherobacter" sbsr008, an enormously diverse array of fatty acids (fas) was found. the distribution of straight-chain fatty acids (scfas) and branched-chain fatty acids (bcfas) supports the reported clustering of strains in the phylogenetic tree based on 16s rrna genes. this finding additionally allows the prediction and assignment of the ...201121317327
enzymatic and mutational analyses of a class ii 3',5'-cyclic nucleotide phosphodiesterase, pdee, from myxococcus xanthus.myxococcus xanthus pdee, an enzyme homologous to class ii 3',5'-cyclic nucleotide phosphodiesterases, hydrolyzed cyclic amp (camp) and cgmp with k(m) values of 12 µm and 25 µm, respectively. a pdee mutant exhibited delays in fruiting body and spore formation compared with the wild type when cultured on starvation medium.201121317337
unusual outer membrane lipid composition of the gram-negative, lipopolysaccharide-lacking myxobacterium sorangium cellulosum so ce56.the gram-negative myxobacterium sorangium cellulosum so ce56 bears the largest bacterial genome published so far, coding for nearly 10,000 genes. careful analysis of this genome data revealed that part of the genes coding for the very well conserved biosynthesis of lipopolysaccharides (lps) are missing in this microbe. biochemical analysis gave no evidence for the presence of lps in the membranes of so ce56. by analyzing the lipid composition of its outer membrane sphingolipids were identified a ...201121321121
enzymatic and functional analysis of a protein phosphatase, pph3, from myxococcus xanthus.a protein phosphatase, designated pph3, from myxococcus xanthus showed the enzymatic characteristics of pp2c-type serine/threonine protein phosphatases, which are metal ion-dependent, okadaic acid-insensitive protein phosphatases. the pph3 mutant under starvation conditions formed immature fruiting bodies and reduced sporulation.201121398555
microtubule binding and disruption and induction of premature senescence by disorazole c(1).disorazoles comprise a family of 29 macrocyclic polyketides isolated from the fermentation broth of the myxobacterium sorangium cellulosum. the major fermentation product, disorazole a(1), was found previously to irreversibly bind to tubulin and to have potent cytotoxic activity against tumor cells, possibly because of its highly electrophilic epoxide moiety. to test this hypothesis, we synthesized the epoxide-free disorazole c(1) and found it retained potent antiproliferative activity against t ...200919066338
phylogenetic distribution and evolutionary history of bacterial dead-box proteins.dead-box proteins are found in all domains of life and participate in almost all cellular processes that involve rna. the presence of dead and helicase_c conserved domains distinguish these proteins. dead-box proteins exhibit rna-dependent atpase activity in vitro, and several also show rna helicase activity. in this study, we analyzed the distribution and architecture of dead-box proteins among bacterial genomes to gain insight into the evolutionary pathways that have shaped their history. we i ...201121437710
isolation of xylose isomerases by sequence- and function-based screening from a soil metagenome library.abstract: background: xylose isomerase (xi) catalyses the isomerization of xylose to xylulose in bacteria and some fungi. currently, only a limited number of xi genes have been functionally expressed in saccharomyces cerevisiae, the microorganism of choice for lignocellulosic ethanol production. the objective of the present study was to search for novel xi genes in the vastly diverse microbial habitat present in soil. as the exploitation of microbial diversity is impaired by the ability to culti ...201121545702
high-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in escherichia coli.background: artemisinin derivatives are the key active ingredients in artemisinin combination therapies (acts), the most effective therapies available for treatment of malaria. because the raw material is extracted from plants with long growing seasons, artemisinin is often in short supply, and fermentation would be an attractive alternative production method to supplement the plant source. previous work showed that high levels of amorpha-4,11-diene, an artemisinin precursor, can be made in esch ...200919221601
widespread occurrence of secondary lipid biosynthesis potential in microbial lineages.bacterial production of long-chain omega-3 polyunsaturated fatty acids (pufas), such as eicosapentaenoic acid (epa, 20:5n-3) and docosahexaenoic acid (dha, 22:6n-3), is constrained to a narrow subset of marine γ-proteobacteria. the genes responsible for de novo bacterial pufa biosynthesis, designated pfaeabcd, encode large, multi-domain protein complexes akin to type i iterative fatty acid and polyketide synthases, herein referred to as "pfa synthases". in addition to the archetypal pfa synthase ...201121629834
structural insights into the function of aminoglycoside-resistance a1408 16s rrna methyltransferases from antibiotic-producing and human pathogenic bacteria.x-ray crystal structures were determined of the broad-spectrum aminoglycoside-resistance a1408 16s rrna methyltransferases kamb and npma, from the aminoglycoside-producer streptoalloteichus tenebrarius and human pathogenic escherichia coli, respectively. consistent with their common function, both are class i methyltransferases with additional highly conserved structural motifs that embellish the core sam-binding fold. in overall structure, the a1408 rrna methyltransferase were found to be most ...201020639535
formation and characterization of acyl carrier protein-linked polyketide synthase extender units.polyketide natural products are assembled by the condensation of an initiating precursor, or starter unit, with a series of additional precursors referred to as extender units. while there are a number of polyketide synthase starter units, there are currently only seven known polyketide synthase extender units. polyketide synthase extender units thioesterified to coenzyme a have been known for some time; however, polyketide synthase extender units thioesterified to acyl carrier proteins (acps) h ...200919362639
a new family of bacterial condensins.condensins play a central role in global chromatin organization. in bacteria, two families of condensins have been identified, the mukbef and smc-scpab complexes. only one of the two complexes is usually found in a given species, giving rise to a paradigm that a single condensin organizes bacterial chromosomes. using sequence analysis, we identified a third family of condensins, mksbef (mukbef-like smc proteins), which is broadly present in diverse bacteria. the proteins appear distantly related ...201121752107
core proteome of the minimal cell: comparative proteomics of three mollicute species.mollicutes (mycoplasmas) have been recognized as highly evolved prokaryotes with an extremely small genome size and very limited coding capacity. thus, they may serve as a model of a 'minimal cell': a cell with the lowest possible number of genes yet capable of autonomous self-replication. we present the results of a comparative analysis of proteomes of three mycoplasma species: a. laidlawii, m. gallisepticum, and m. mobile. the core proteome components found in the three mycoplasma species are ...201121818284
the biofilm inhibitor carolacton disturbs membrane integrity and cell division of streptococcus mutans through the serine-threonine proteinkinase pknb.carolacton, a secondary metabolite isolated from the myxobacterium sorangium cellulosum, disturbs s. mutans biofilm viability at nanomolar concentrations. here we show that carolacton causes leakage of cytoplasmic content (dna and proteins) in growing cells at low ph and provide quantitative data on the membrane damage. furthermore we demonstrate that the biofilm specific activity of carolacton is due to the strong acidification occurring during biofilm growth. the chemical conversion of the ket ...201121840978
insertion of horizontally transferred genes within conserved syntenic regions of yeast genomes.horizontal gene transfer has been occasionally mentioned in eukaryotic genomes, but such events appear much less numerous than in prokaryotes, where they play important functional and evolutionary roles. in yeasts, few independent cases have been described, some of which corresponding to major metabolic functions, but no systematic screening of horizontally transferred genes has been attempted so far. taking advantage of the synteny conservation among five newly sequenced and annotated genomes o ...200919654869
bioprospecting metagenomics of decaying wood: mining for new glycoside hydrolases.abstract:201121816041
emerging roles for the ro 60-kda autoantigen in noncoding rna metabolism.all cells contain an enormous variety of ribonucleoprotein (rnp) complexes that function in diverse processes. although the mechanisms by which many of these rnps contribute to cell metabolism are well understood, the roles of others are only now beginning to be revealed. a member of this latter category, the ro 60-kda protein and its associated noncoding y rnas, was discovered because the protein component is a frequent target of the autoimmune response in patients with the rheumatic diseases s ...201121823229
geographic distribution of secondary metabolite genes in the marine actinomycete salinispora arenicola.the molecular fingerprinting technique terminal-restriction fragment length polymorphism (t-rflp) was used in combination with sequence-based approaches to evaluate the geographic distribution of secondary metabolite biosynthetic genes in strains of the marine actinomycete salinispora arenicola. this study targeted ketosynthase (ks) domains from type i polyketide synthase (pks) genes and revealed four distinct clusters, the largest of which was comprised of strains from all six global locations ...201121724881
no formation by a catalytically self-sufficient bacterial nitric oxide synthase from sorangium cellulosum.the role of nitric oxide (no) in the host response to infection and in cellular signaling is well established. enzymatic synthesis of no is catalyzed by the nitric oxide synthases (noss), which convert arg into no and citrulline using co-substrates o2 and nadph. mammalian nos contains a flavin reductase domain (fad and fmn) and a catalytic heme oxygenase domain (p450-type heme and tetrahydrobiopterin). bacterial noss, while much less studied, were previously identified as only containing the hem ...200919805284
regio- and stereospecificity of filipin hydroxylation sites revealed by crystal structures of cytochrome p450 105p1 and 105d6 from streptomyces avermitilis.the polyene macrolide antibiotic filipin is widely used as a probe for cholesterol and a diagnostic tool for type c niemann-pick disease. two position-specific p450 enzymes are involved in the post-polyketide modification of filipin during its biosynthesis, thereby providing molecular diversity to the "filipin complex." cyp105p1 and cyp105d6 from streptomyces avermitilis, despite their high sequence similarities, catalyze filipin hydroxylation at different positions, c26 and c1', respectively. h ...201020375018
characterization of novel ompa-like protein of leptospira interrogans that binds extracellular matrix molecules and plasminogen.leptospira interrogans is the etiological agent of leptospirosis, a zoonotic disease of human and veterinary concern. the identification of novel proteins that mediate host-pathogen interactions is important for understanding the bacterial pathogenesis as well as to identify protective antigens that would help fight the disease. we describe in this work the cloning, expression, purification and characterization of three predicted leptospiral membrane proteins, lic10258, lic12880 (lp30) and lic12 ...201121755014
Gating NO Release from Nitric Oxide Synthase.We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV-vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for ...201122148177
Gating NO Release from Nitric Oxide Synthase.We have investigated the kinetics of NO escape from Geobacillus stearothermophilus nitric oxide synthase (gsNOS). Previous work indicated that NO release was gated at position 223 in mammalian enzymes; our kinetics experiments include mutants at that position along with measurements on the wild type enzyme. Employing stopped-flow UV-vis methods, reactions were triggered by mixing a reduced enzyme/N-hydroxy-l-arginine complex with an aerated buffer solution. NO release kinetics were obtained for ...201122148177
a novel cold-adapted lipase from sorangium cellulosum strain so0157-2: gene cloning, expression, and enzymatic characterization.genome sequencing of cellulolytic myxobacterium sorangium cellulosum reveals many open-reading frames (orfs) encoding various degradation enzymes with low sequence similarity to those reported, but none of them has been characterized. in this paper, a predicted lipase gene (lipa) was cloned from s. cellulosum strain so0157-2 and characterized. lipa is 981-bp in size, encoding a polypeptide of 326 amino acids that contains the pentapeptide (ghsmg) and catalytic triad residues (ser114, asp250 and ...201122072918
from complete genome sequence to 'complete' understanding?the rapidly accumulating genome sequence data allow researchers to address fundamental biological questions that were not even asked just a few years ago. a major problem in genomics is the widening gap between the rapid progress in genome sequencing and the comparatively slow progress in the functional characterization of sequenced genomes. here we discuss two key questions of genome biology: whether we need more genomes, and how deep is our understanding of biology based on genomic analysis. w ...201020647113
complete genome sequence of haliangium ochraceum type strain (smp-2).haliangium ochraceum fudou et al. 2002 is the type species of the genus haliangium in the myxococcal family 'haliangiaceae'. members of the genus haliangium are the first halophilic myxobacterial taxa described. the cells of the species follow a multicellular lifestyle in highly organized biofilms, called swarms, they decompose bacterial and yeast cells as most myxobacteria do. the fruiting bodies contain particularly small coccoid myxospores. h. ochraceum encodes the first actin homologue ident ...201021304682
identification of the biosynthetic gene cluster for the pacidamycin group of peptidyl nucleoside antibiotics.pacidamycins are a family of uridyl tetra/pentapeptide antibiotics that act on the translocase mray to block bacterial cell wall assembly. to elucidate the biosynthetic logic of pacidamcyins, a putative gene cluster was identified by 454 shotgun genome sequencing of the producer streptomyces coeruleorubidus nrrl 18370. the 31-kb gene cluster encodes 22 proteins (paca-v), including highly dissociated nonribosomal peptide synthetase (nrps) modules and a variety of tailoring enzymes. gene deletions ...201020826445
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