Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
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| evolution of dna ligases of nucleo-cytoplasmic large dna viruses of eukaryotes: a case of hidden complexity. | eukaryotic nucleo-cytoplasmic large dna viruses (ncldv) encode most if not all of the enzymes involved in their dna replication. it has been inferred that genes for these enzymes were already present in the last common ancestor of the ncldv. however, the details of the evolution of these genes that bear on the complexity of the putative ancestral ncldv and on the evolutionary relationships between viruses and their hosts are not well understood. | 2009 | 20021668 |
| horizontal gene transfer of zinc and non-zinc forms of bacterial ribosomal protein s4. | the universal ribosomal protein s4 is essential for the initiation of small subunit ribosomal assembly and translational accuracy. being part of the information processing machinery of the cell, the gene for s4 is generally thought of as being inherited vertically and has been used in concatenated gene phylogenies. here we report the evolution of ribosomal protein s4 in relation to a broad sharing of zinc/non-zinc forms of the gene and study the scope of horizontal gene transfer (hgt) of s4 duri ... | 2009 | 19640295 |
| 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 ... | 2009 | 19066338 |
| 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 ... | 2009 | 19066338 |
| 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 ... | 2009 | 19067453 |
| 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 ... | 2009 | 19126236 |
| 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 ... | 2009 | 19221601 |
| 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 ... | 2009 | 19233926 |
| 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 ... | 2009 | 19362639 |
| 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 ... | 2009 | 19387496 |
| 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. | 2009 | 19480720 |
| 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 ... | 2009 | 19654869 |
| 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 ... | 2009 | 19696019 |
| 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 ... | 2009 | 19706604 |
| 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 ... | 2009 | 19805284 |
| 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 ... | 2009 | 19821963 |
| metronomic dosing enhances the anti-angiogenic effect of epothilone b. | background: high doses (10nm) of epothilone b, a microtubule stabilizer, will inhibit the development of human tumor-derived angiogenesis following short (14 d) drug exposure times. metronomic dosing regimes use lower drug doses and prolonged drug exposure times in an attempt to decrease toxicity compared with standard dosing schedules. we hypothesized that epothilone b would be an effective anti-angiogenic agent when administered at very low doses over an extended period of time. methods: fragm ... | 2009 | 20338584 |
| metronomic dosing enhances the anti-angiogenic effect of epothilone b. | background: high doses (10nm) of epothilone b, a microtubule stabilizer, will inhibit the development of human tumor-derived angiogenesis following short (14 d) drug exposure times. metronomic dosing regimes use lower drug doses and prolonged drug exposure times in an attempt to decrease toxicity compared with standard dosing schedules. we hypothesized that epothilone b would be an effective anti-angiogenic agent when administered at very low doses over an extended period of time. methods: fragm ... | 2009 | 20338584 |
| 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 ... | 2009 | 19011080 |
| 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 ... | 2009 | 19011080 |
| 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 ... | 2010 | 20371514 |
| 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 ... | 2010 | 20375018 |
| 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 ... | 2010 | 20382816 |
| 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 ... | 2010 | 20400851 |
| 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 ... | 2010 | 20406823 |
| a multi-protein complex from myxococcus xanthus required for bacterial gliding motility. | myxococcus xanthus moves by gliding motility powered by type iv pili (s-motility) and a second motility system, a-motility, whose mechanism remains elusive despite the identification of approximately 40 a-motility genes. in this study, we used biochemistry and cell biology analyses to identify multi-protein complexes associated with a-motility. previously, we showed that the n-terminal domain of frzcd, the receptor for the frizzy chemosensory pathway, interacts with two a-motility proteins, aglz ... | 2010 | 20487265 |
| using chemobiosynthesis and synthetic mini-polyketide synthases to produce pharmaceutical intermediates in escherichia coli. | recombinant microbial whole-cell biocatalysis is a valuable approach for producing enantiomerically pure intermediates for the synthesis of complex molecules. here, we describe a method to produce polyketide intermediates possessing multiple stereogenic centers by combining chemobiosynthesis and engineered mini-polyketide synthases (pkss). chemobiosynthesis allows the introduction of unnatural moieties, while a library of synthetic bimodular pkss expressed from codon-optimized genes permits the ... | 2010 | 20543042 |
| the phosphatomes of the multicellular myxobacteria myxococcus xanthus and sorangium cellulosum in comparison with other prokaryotic genomes. | analysis of the complete genomes from the multicellular myxobacteria myxococcus xanthus and sorangium cellulosum identified the highest number of eukaryotic-like protein kinases (elks) compared to all other genomes analyzed. high numbers of protein phosphatases (pps) could therefore be anticipated, as reversible protein phosphorylation is a major regulation mechanism of fundamental biological processes. | 2010 | 20567509 |
| the bridge-region of the ku superfamily is an atypical zinc ribbon domain. | members of the ku superfamily are dna-end-binding proteins involved in non-homologous end-joining (nhej) dna repair. the published crystal structure of human ku-dna complex reveals a heterodimer that forms a ring around dsdna by means of the ku core modules. these modules contain a highly conserved seven-stranded β-barrel, which in turn contains an insertion, termed the bridge-region, between its second and third β-strands. the bridge-region adopts an unusual β-strand-rich structure critical for ... | 2010 | 20580930 |
| discovery and total synthesis of a new estrogen receptor heterodimerizing actinopolymorphol a from actinopolymorpha rutilus. | estrogen receptor eralpha and erbeta heterodimerization has been implicated in cancer chemoprevention. the discovery, structural elucidation, and total synthesis of a new natural product, actinopolymorphol a (1), from actinopolymorpha rutilus (yim45725) that preferentially induces eralpha/beta heterodimerization is reported. total synthesis of 1 has allowed us to determine its absolute stereochemistry and that of a previously known deacetylated congener, and 1 represents the first member of a ne ... | 2010 | 20593804 |
| 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 ... | 2010 | 20639535 |
| 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 ... | 2010 | 20647113 |
| 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. | 2010 | 20659313 |
| 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 ... | 2010 | 20826445 |
| 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 ... | 2010 | 20851978 |
| engineered polyketide biosynthesis and biocatalysis in escherichia coli. | polyketides are important bioactive natural products biosynthesized by bacteria, fungi, and plants. the enzymes that synthesize polyketides are collectively referred to as polyketide synthases (pkss). because many of the natural hosts that produce polyketides are difficult to culture or manipulate, establishing a universal heterologous host that is genetically tractable has become an important goal toward the engineered biosynthesis of polyketides and analogues. here, we summarize the recent pro ... | 2010 | 20853106 |
| structural and biochemical characterization of mycobacterium tuberculosis cyp142: evidence for multiple cholesterol 27-hydroxylase activities in a human pathogen. | the mycobacterium tuberculosis cytochrome p450 enzyme cyp142 is encoded in a large gene cluster involved in metabolism of host cholesterol. cyp142 was expressed and purified as a soluble, low spin p450 hemoprotein. cyp142 binds tightly to cholesterol and its oxidized derivative cholest-4-en-3-one, with extensive shift of the heme iron to the high spin state. high affinity for azole antibiotics was demonstrated, highlighting their therapeutic potential. cyp142 catalyzes either 27-hydroxylation of ... | 2010 | 20889498 |
| 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% ( ... | 2010 | 20948900 |
| 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 ... | 2010 | 21083931 |
| 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. | 2010 | 21187861 |
| 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 ... | 2010 | 19915043 |
| 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 ... | 2010 | 19915043 |
| presence of a classical rrm-fold palm domain in thg1-type 3'- 5'nucleic acid polymerases and the origin of the ggdef and crispr polymerase domains. | almost all known nucleic acid polymerases catalyze 5'-3' polymerization by mediating the attack on an incoming nucleotide 5' triphosphate by the 3'oh from the growing polynucleotide chain in a template dependent or independent manner. the only known exception to this rule is the thg1 rna polymerase that catalyzes 3'-5' polymerization in vitro and also in vivo as a part of the maturation process of histidinyl trna. while the initial reaction catalyzed by thg1 has been compared to adenylation cata ... | 2010 | 20591188 |
| identifying a resistance determinant for the antimitotic natural products disorazole c1 and a1. | disorazoles are macrocyclic polyketides first isolated from the fermentation broth of the myxobacterium sorangium cellulosum. both the major fermentation product disorazole a(1) and its much rarer companion disorazole c(1) exhibit potent cytotoxic activity against many human tumor cells. furthermore, the disorazoles appear to bind tubulin uniquely among known antimitotic agents, promoting apoptosis or premature senescence. it is uncertain what conveys tumor cell sensitivity to these complex natu ... | 2010 | 20008956 |
| biosynthesis of rhizocticins, antifungal phosphonate oligopeptides produced by bacillus subtilis atcc6633. | rhizocticins are phosphonate oligopeptide antibiotics containing the c-terminal nonproteinogenic amino acid (z)-l-2-amino-5-phosphono-3-pentenoic acid (appa). here we report the identification and characterization of the rhizocticin biosynthetic gene cluster (rhi) in bacillus subtilis atcc6633. rhizocticin b was heterologously produced in the nonproducer strain bacillus subtilis 168. a biosynthetic pathway is proposed on the basis of bioinformatics analysis of the rhi genes. one of the steps dur ... | 2010 | 20142038 |
| sequence-based analysis of secondary-metabolite biosynthesis in marine actinobacteria. | a diverse collection of 60 marine-sediment-derived actinobacteria representing 52 operational taxonomic units was screened by pcr for genes associated with secondary-metabolite biosynthesis. three primer sets were employed to specifically target adenylation domains associated with nonribosomal peptide synthetases (nrpss) and ketosynthase (ks) domains associated with type i modular, iterative, hybrid, and enediyne polyketide synthases (pkss). in total, two-thirds of the strains yielded a sequence ... | 2010 | 20154113 |
| 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 ... | 2010 | 21304682 |
| distinguishing microbial genome fragments based on their composition: evolutionary and comparative genomic perspectives. | it is well known that patterns of nucleotide composition vary within and among genomes, although the reasons why these variations exist are not completely understood. between-genome compositional variation has been exploited to assign environmental shotgun sequences to their most likely originating genomes, whereas within-genome variation has been used to identify recently acquired genetic material such as pathogenicity islands. recent sequence assignment techniques have achieved high levels of ... | 2010 | 20333228 |
| prokaryote-derived protein inhibitors of peptidases: a sketchy occurrence and mostly unknown function. | in metazoan organisms protein inhibitors of peptidases are important factors essential for regulation of proteolytic activity. in vertebrates genes encoding peptidase inhibitors constitute up to 1% of genes reflecting a need for tight and specific control of proteolysis especially in extracellular body fluids. in stark contrast unicellular organisms, both prokaryotic and eukaryotic consistently contain only few, if any, genes coding for putative peptidase inhibitors. this may seem perplexing in ... | 2010 | 20558234 |
| in silico characterization of pectate lyase protein sequences from different source organisms. | a total of 121 protein sequences of pectate lyases were subjected to homology search, multiple sequence alignment, phylogenetic tree construction, and motif analysis. the phylogenetic tree constructed revealed different clusters based on different source organisms representing bacterial, fungal, plant, and nematode pectate lyases. the multiple accessions of bacterial, fungal, nematode, and plant pectate lyase protein sequences were placed closely revealing a sequence level similarity. the multip ... | 2010 | 21048874 |
| chemotherapy resistance in metastatic breast cancer: the evolving role of ixabepilone. | resistance to chemotherapy is a major obstacle to the effective treatment of many tumor types. although many anticancer therapies can alter tumor growth, in most cases the effect is not long lasting. consequently, there is a significant need for new agents with low susceptibility to common drug resistance mechanisms in order to improve response rates and potentially extend survival. approximately 30% of the women diagnosed with early-stage disease in turn progress to metastatic breast cancer, fo ... | 2010 | 21050423 |
| prediction and analysis of the modular structure of cytochrome p450 monooxygenases. | cytochrome p450 monooxygenases (cyps) form a vast and diverse family of highly variable sequences. they catalyze a wide variety of oxidative reactions and are therefore of great relevance in drug development and biotechnological applications. despite their differences in sequence and substrate specificity, the structures of cyps are highly similar. although being in research focus for years, factors mediating selectivity and activity remain vague. | 2010 | 20950472 |
| conformational plasticity and structure/function relationships in cytochromes p450. | the cytochrome p450s are a superfamily of enzymes that are found in all kingdoms of living organisms, and typically catalyze the oxidative addition of atomic oxygen to an unactivated c-c or c-h bond. over 8000 nonredundant sequences of putative and confirmed p450 enzymes have been identified, but three-dimensional structures have been determined for only a small fraction of these. while all p450 enzymes for which structures have been determined share a common global fold, the flexibility and mod ... | 2010 | 20446763 |
| endometrial carcinoma: a review of chemotherapy, drug resistance, and the search for new agents. | adenocarcinoma of the endometrium represents the most common gynecologic malignancy in developed countries. although early-stage cancers are effectively treated surgically, commonly without adjuvant therapy, the treatment of high-risk and advanced disease is more complex. chemotherapy has evolved into an important modality in high-risk early-stage and advanced-stage disease, and in recurrent endometrial cancer. taxane-based therapy consistently demonstrates the highest response rates in the firs ... | 2010 | 20930101 |
| microtubule-binding agents: a dynamic field of cancer therapeutics. | microtubules are dynamic filamentous cytoskeletal proteins composed of tubulin and are an important therapeutic target in tumour cells. agents that bind to microtubules have been part of the pharmacopoeia of anticancer therapy for decades and until the advent of targeted therapy, microtubules were the only alternative to dna as a therapeutic target in cancer. the screening of a range of botanical species and marine organisms has yielded promising new antitubulin agents with novel properties. in ... | 2010 | 20885410 |
| optimizing ixabepilone treatment schedules in patients with advanced or metastatic breast cancer. | the epothilone b analog, ixabepilone, demonstrates low susceptibility to drug resistance mechanisms and has demonstrated clinically meaningful efficacy in patients refractory to other chemotherapeutic options. ixabepilone is approved by the fda for treatment of patients with metastatic breast cancer (mbc) progressing after taxanes and anthracyclines, either in combination with capecitabine or as monotherapy if the patient has already progressed on capecitabine. ixabepilone is generally well tole ... | 2010 | 20886213 |
| detecting and understanding the roles of nitric oxide in biology. | we are pursuing a dual strategy for investigating the chemistry of nitric oxide as a biological signaling agent. in one approach, metal-based fluorescent sensors for the detection of no in living cells are evaluated, and a sensor based on a copper fluorescein complex has proved to be a valuable lead compound. sensors of this class permit identification of no from both inducible and constitutive forms of nitric oxide synthase and facilitate investigation of different no functions in response to e ... | 2010 | 20666391 |
| read length and repeat resolution: exploring prokaryote genomes using next-generation sequencing technologies. | there are a growing number of next-generation sequencing technologies. at present, the most cost-effective options also produce the shortest reads. however, even for prokaryotes, there is uncertainty concerning the utility of these technologies for the de novo assembly of complete genomes. this reflects an expectation that short reads will be unable to resolve small, but presumably abundant, repeats. | 2010 | 20634954 |
| identification of the viridicatumtoxin and griseofulvin gene clusters from penicillium aethiopicum. | penicillium aethiopicum produces two structurally interesting and biologically active polyketides: the tetracycline-like viridicatumtoxin 1 and the classic antifungal agent griseofulvin 2. here, we report the concurrent discovery of the two corresponding biosynthetic gene clusters (vrt and gsf) by 454 shotgun sequencing. gene deletions confirmed that two nonreducing pkss (nrpkss), vrta and gsfa, are required for the biosynthesis of 1 and 2, respectively. both pkss share similar domain architectu ... | 2010 | 20534346 |
| ixabepilone as monotherapy or in combination for the treatment of advanced breast cancer. | advanced breast cancer represents a therapeutic challenge for oncologists. chemotherapy with anthracyclines and taxanes has improved survival in this setting, but resistant and refractory disease is common. ixabepilone, an epothilone, is a recently approved chemotherapeutic agent, both as a single agent and in combination with capecitabine, with efficacy in patients with resistant advanced disease. in this review, the distinctive properties of this drug are discussed, as well as the clinical evi ... | 2010 | 24367163 |
| the mixed lineage nature of nitrogen transport and assimilation in marine eukaryotic phytoplankton: a case study of micromonas. | the prasinophyte order mamiellales contains several widespread marine picophytoplankton (≤ 2 μm diameter) taxa, including micromonas and ostreococcus. complete genome sequences are available for two micromonas isolates, ccmp1545 and rcc299. we performed in silico analyses of nitrogen transporters and related assimilation genes in ccmp1545 and rcc299 and compared these with other green lineage organisms as well as chromalveolata, fungi, bacteria, and archaea. phylogenetic reconstructions of ammon ... | 2010 | 20457585 |
| a phase i/ii trial and pharmacokinetic study of ixabepilone in adult patients with recurrent high-grade gliomas. | ixabepilone is an epothilone, a novel class of non-taxane microtubule stabilizing agents. a phase i/ii and pharmacokinetic trial of ixabepilone was conducted in patients with recurrent high-grade gliomas. adult patients received ixabepilone as a 1-h infusion daily for 5 days every 3 weeks. a modified continual reassessment method was used to escalate doses, beginning at 5.0 mg/m(2), in patients stratified by use or non-use of enzyme inducing antiepileptic drugs (eiaed). in the phase i study, the ... | 2010 | 20449631 |
| recognition of (2s)-aminomalonyl-acyl carrier protein (acp) and (2r)-hydroxymalonyl-acp by acyltransferases in zwittermicin a biosynthesis. | polyketide synthases elongate a polyketide backbone by condensing carboxylic acid precursors that are thioesterified to either coenzyme a or an acyl carrier protein (acp). two of the three known acp-linked extender units, (2s)-aminomalonyl-acp and (2r)-hydroxymalonyl-acp, are found in the biosynthesis of the agriculturally important antibiotic zwittermicin a. we previously reconstituted the formation of (2s)-aminomalonyl-acp and (2r)-hydroxymalonyl-acp from the primary metabolites l-serine and 1 ... | 2010 | 20353188 |
| phase i trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary. | ixabepilone is a semisynthetic epothilone b analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer. we carried out a phase i trial of ixabepilone plus pegylated liposomal doxorubicin (pld) in patients with advanced taxane-pretreated ovarian and breast cancer. | 2010 | 20357034 |
| mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole c1. | disorazoles are polyene macrodiolides isolated from a myxobacterium fermentation broth. disorazole c1 was newly synthesized and found to depolymerize microtubules and cause mitotic arrest. here we examined the cellular responses to disorazole c1 in both non-cancer and cancer cells and compared our results to vinblastine and taxol. | 2010 | 20181182 |
| a phase ii trial of the epothilone b analog ixabepilone (bms-247550) in patients with metastatic melanoma. | ixabepilone (bms-247550), an epothilone b analog, is a microtubule stabilizing agent which has shown activity in several different tumor types and preclinical models in melanoma. in an open label, one-arm, multi-center phase ii trial the efficacy and toxicity of this epothilone was investigated in two different cohorts: chemotherapy-naïve (previously untreated) and previously treated patients with metastatic melanoma. | 2010 | 20098694 |
| total synthesis and evaluation of c26-hydroxyepothilone d derivatives for photoaffinity labeling of beta-tubulin. | three photoaffinity labeled derivatives of epothilone d were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building blocks. the key step for the asymmetric synthesis of (s,e)-3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)pent-4-enal involved a ketone reduction with (r)-me-cbs-oxazaborolidine. for the synthesis of (5s)-5,7-di[(tert-butyldimethylsilyl)oxy]-4,4-dimethylheptan-3-one an asymmetric noyor ... | 2010 | 19954175 |
| tir domain-containing adaptor sarm is a late addition to the ongoing microbe-host dialog. | toll/interleukin-1 receptor (tir) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein-protein interactions. among them is sarm, the only tir domain-containing adaptor that can negatively regulate tlr signaling. by extensive phylogenetic analysis, we show here that sarm is closely related to bacterial proteins with tir domains, suggesting that this family has a different ... | 2010 | 21110998 |
| tir domain-containing adaptor sarm is a late addition to the ongoing microbe-host dialog. | toll/interleukin-1 receptor (tir) domain-containing proteins play important roles in defense against pathogens in both animals and plants, connecting the immunity signaling pathways via a chain of specific protein-protein interactions. among them is sarm, the only tir domain-containing adaptor that can negatively regulate tlr signaling. by extensive phylogenetic analysis, we show here that sarm is closely related to bacterial proteins with tir domains, suggesting that this family has a different ... | 2010 | 21110998 |
| networks of gene sharing among 329 proteobacterial genomes reveal differences in lateral gene transfer frequency at different phylogenetic depths. | lateral gene transfer (lgt) is an important mechanism of natural variation among prokaryotes. over the full course of evolution, most or all of the genes resident in a given prokaryotic genome have been affected by lgt, yet the frequency of lgt can vary greatly across genes and across prokaryotic groups. the proteobacteria are among the most diverse of prokaryotic taxa. the prevalence of lgt in their genome evolution calls for the application of network-based methods instead of tree-based method ... | 2010 | 21059789 |
| networks of gene sharing among 329 proteobacterial genomes reveal differences in lateral gene transfer frequency at different phylogenetic depths. | lateral gene transfer (lgt) is an important mechanism of natural variation among prokaryotes. over the full course of evolution, most or all of the genes resident in a given prokaryotic genome have been affected by lgt, yet the frequency of lgt can vary greatly across genes and across prokaryotic groups. the proteobacteria are among the most diverse of prokaryotic taxa. the prevalence of lgt in their genome evolution calls for the application of network-based methods instead of tree-based method ... | 2010 | 21059789 |
| molecular evolution and the role of oxidative stress in the expansion and functional diversification of cytosolic glutathione transferases. | cytosolic glutathione transferases (cgst) are a large group of ubiquitous enzymes involved in detoxification and are well known for their undesired side effects during chemotherapy. in this work we have performed thorough phylogenetic analyses to understand the various aspects of the evolution and functional diversification of cgsts. furthermore, we assessed plausible correlations between gene duplication and substrate specificity of gene paralogs in humans and selected species, notably in mamma ... | 2010 | 20843339 |
| myxobacteria, polarity, and multicellular morphogenesis. | myxobacteria are renowned for the ability to sporulate within fruiting bodies whose shapes are species-specific. the capacity to build those multicellular structures arises from the ability of m. xanthus to organize high cell-density swarms, in which the cells tend to be aligned with each other while constantly in motion. the intrinsic polarity of rod-shaped cells lays the foundation, and each cell uses two polar engines for gliding on surfaces. it sprouts retractile type iv pili from the leadin ... | 2010 | 20610548 |
| phylogenomic evidence for a myxococcal contribution to the mitochondrial fatty acid beta-oxidation. | the origin of eukaryotes remains a fundamental question in evolutionary biology. although it is clear that eukaryotic genomes are a chimeric combination of genes of eubacterial and archaebacterial ancestry, the specific ancestry of most eubacterial genes is still unknown. the growing availability of microbial genomes offers the possibility of analyzing the ancestry of eukaryotic genomes and testing previous hypotheses on their origins. | 2011 | 21760940 |
| xenobiotic efflux in bacteria and fungi: a genomics update. | 2011 | 21692371 | |
| bioinformatic analysis reveals high diversity of bacterial genes for laccase-like enzymes. | fungal laccases have been used in various fields ranging from processes in wood and paper industries to environmental applications. although a few bacterial laccases have been characterized in recent years, prokaryotes have largely been neglected as a source of novel enzymes, in part due to the lack of knowledge about the diversity and distribution of laccases within bacteria. in this work genes for laccase-like enzymes were searched for in over 2,200 complete and draft bacterial genomes and fou ... | 2011 | 22022440 |
| new target for inhibition of bacterial rna polymerase: 'switch region'. | a new drug target - the 'switch region' - has been identified within bacterial rna polymerase (rnap), the enzyme that mediates bacterial rna synthesis. the new target serves as the binding site for compounds that inhibit bacterial rna synthesis and kill bacteria. since the new target is present in most bacterial species, compounds that bind to the new target are active against a broad spectrum of bacterial species. since the new target is different from targets of other antibacterial agents, com ... | 2011 | 21862392 |
| antibiotics trapping transcription initiation intermediates: to melt or to bend, what's first? | promoter dna melting, culminating in the loading of the single-stranded dna template into the rna polymerase active site, is a key step in transcription initiation. recently, the first transcription inhibitors found to block distinct steps of promoter melting were characterized. here, the impact of these studies is discussed with respect to the current models of transcription initiation. | 2011 | 21468230 |
| (+)-sorangicin a: evolution of a viable synthetic strategy. | an effective, asymmetric total synthesis of the antibiotic (+)-sorangicin a (1) has been achieved. central to this venture was the development of first and second generation syntheses of the signature dioxabicyclo[3.2.1]octane core, the first featuring chemo- and stereoselective epoxide ring openings facilitated by a co(2)(co)(6)-alkyne complex, the second involving a khmds-promoted epoxide ring formation/opening cascade. additional highlights include effective construction of the dihydro- and t ... | 2011 | 22247573 |
| nuclear export of proteins and drug resistance in cancer. | the intracellular location of a protein is crucial to its normal functioning in a cell. cancer cells utilize the normal processes of nuclear-cytoplasmic transport through the nuclear pore complex of a cell to effectively evade anti-neoplastic mechanisms. crm1-mediated export is increased in various cancers. proteins that are exported in cancer include tumor-suppressive proteins such as retinoblastoma, apc, p53, brac1, foxo proteins, ini1/hsnf5, galectin-3, bok, nucleophosmin, rassf2, merlin, p21 ... | 2011 | 22209898 |
| nuclear export of proteins and drug resistance in cancer. | the intracellular location of a protein is crucial to its normal functioning in a cell. cancer cells utilize the normal processes of nuclear-cytoplasmic transport through the nuclear pore complex of a cell to effectively evade anti-neoplastic mechanisms. crm1-mediated export is increased in various cancers. proteins that are exported in cancer include tumor-suppressive proteins such as retinoblastoma, apc, p53, brac1, foxo proteins, ini1/hsnf5, galectin-3, bok, nucleophosmin, rassf2, merlin, p21 ... | 2011 | 22209898 |
| beyond taxanes: the next generation of microtubule-targeting agents. | taxanes are a standard first-line option for metastatic breast cancer (mbc), but their utility may be limited by primary or acquired resistance. new microtubule-targeting agents have been developed to overcome taxane resistance and provide additional options for improving patient outcomes. this article reviews these alternative microtubule-targeting agents and their potential clinical benefits for mbc patients. relevant clinical data were compiled through searches within pubmed and congress abst ... | 2011 | 22113255 |
| beyond taxanes: the next generation of microtubule-targeting agents. | taxanes are a standard first-line option for metastatic breast cancer (mbc), but their utility may be limited by primary or acquired resistance. new microtubule-targeting agents have been developed to overcome taxane resistance and provide additional options for improving patient outcomes. this article reviews these alternative microtubule-targeting agents and their potential clinical benefits for mbc patients. relevant clinical data were compiled through searches within pubmed and congress abst ... | 2011 | 22113255 |
| phase i clinical, pharmacokinetic, and pharmacodynamic study of kos-862 (epothilone d) in patients with advanced solid tumors and lymphoma. | to determine the maximum tolerated dose and safety of the epothilone, kos-862, in patients with advanced solid tumors or lymphoma. | 2011 | 22072399 |
| phase i clinical, pharmacokinetic, and pharmacodynamic study of kos-862 (epothilone d) in patients with advanced solid tumors and lymphoma. | to determine the maximum tolerated dose and safety of the epothilone, kos-862, in patients with advanced solid tumors or lymphoma. | 2011 | 22072399 |
| enzymatic chemistry of cyclopropane, epoxide, and aziridine biosynthesis. | 2011 | 22017381 | |
| enzymatic chemistry of cyclopropane, epoxide, and aziridine biosynthesis. | 2011 | 22017381 | |
| natural products for cancer chemotherapy. | for over 40 years, natural products have served us well in combating cancer. the main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. the microbes serve as a major source of natural products with anti-tumour activity. a number of these products were first discovered as antibiotics. another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. a vast array of biological metabolites can be obtained from the marine w ... | 2011 | 21375717 |
| solving the problem: genome annotation standards before the data deluge. | the promise of genome sequencing was that the vast undiscovered country would be mapped out by comparison of the multitude of sequences available and would aid researchers in deciphering the role of each gene in every organism. researchers recognize that there is a need for high quality data. however, different annotation procedures, numerous databases, and a diminishing percentage of experimentally determined gene functions have resulted in a spectrum of annotation quality. ncbi in collaboratio ... | 2011 | 22180819 |
| joint scaling laws in functional and evolutionary categories in prokaryotic genomes. | we propose and study a class-expansion/innovation/loss model of genome evolution taking into account biological roles of genes and their constituent domains. in our model, numbers of genes in different functional categories are coupled to each other. for example, an increase in the number of metabolic enzymes in a genome is usually accompanied by addition of new transcription factors regulating these enzymes. such coupling can be thought of as a proportional 'recipe' for genome composition of th ... | 2011 | 21937509 |
| joint scaling laws in functional and evolutionary categories in prokaryotic genomes. | we propose and study a class-expansion/innovation/loss model of genome evolution taking into account biological roles of genes and their constituent domains. in our model, numbers of genes in different functional categories are coupled to each other. for example, an increase in the number of metabolic enzymes in a genome is usually accompanied by addition of new transcription factors regulating these enzymes. such coupling can be thought of as a proportional 'recipe' for genome composition of th ... | 2011 | 21937509 |
| formal synthesis of (+)-sorangicin a. | the formal synthesis of (+)-sorangicin a was completed by two independent routes. both approaches feature a cross metathesis reaction to form the c29-c30 bond to arrive at the bicyclic ether/tetrahydropyran fragment. formation of the c15-c16 olefin to unite the dihydropyran fragment with the rest of the molecule was achieved by either a cross metathesis reaction or a julia-kocienski olefination. | 2011 | 21834570 |
| prombase: a web resource for various genomic features and predicted promoters in prokaryotic genomes. | as more and more genomes are being sequenced, an overview of their genomic features and annotation of their functional elements, which control the expression of each gene or transcription unit of the genome, is a fundamental challenge in genomics and bioinformatics. | 2011 | 21781326 |
| expansion of type ii caax proteases reveals evolutionary origin of γ-secretase subunit aph-1. | intramembrane proteases are responsible for a number of regulated proteolysis events occurring within or near the plasma and intracellular membranes. members of one large and diverse family of putative intramembrane metalloproteases are widely distributed in all domains of life, including the type ii caax prenyl proteases and their prokaryotic homologs with putative bacteriocin-related functions. we used sensitive sequence similarity searches to expand this large cpbp (caax proteases and bacteri ... | 2011 | 21570408 |
| engineering microbial factories for synthesis of value-added products. | microorganisms have become an increasingly important platform for the production of drugs, chemicals, and biofuels from renewable resources. advances in protein engineering, metabolic engineering, and synthetic biology enable redesigning microbial cellular networks and fine-tuning physiological capabilities, thus generating industrially viable strains for the production of natural and unnatural value-added compounds. in this review, we describe the recent progress on engineering microbial factor ... | 2011 | 21526386 |
| discovering the unknown: improving detection of novel species and genera from short reads. | high-throughput sequencing technologies enable metagenome profiling, simultaneous sequencing of multiple microbial species present within an environmental sample. since metagenomic data includes sequence fragments ("reads") from organisms that are absent from any database, new algorithms must be developed for the identification and annotation of novel sequence fragments. homology-based techniques have been modified to detect novel species and genera, but, composition-based methods, have not been ... | 2011 | 21541181 |
| drugs that target dynamic microtubules: a new molecular perspective. | microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. as such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), ... | 2011 | 21381049 |
| recent advances in bacterial heme protein biochemistry. | recent progress in genetics, fed by the burst in genome sequence data, has led to the identification of a host of novel bacterial heme proteins that are now being characterized in structural and mechanistic terms. the following short review highlights very recent work with bacterial heme proteins involved in the uptake, biosynthesis, degradation, and use of heme in respiration and sensing. | 2011 | 21339081 |
| soraphen a, an inhibitor of acetyl coa carboxylase activity, interferes with fatty acid elongation. | acetyl coa carboxylase (acc1 and acc2) generates malonyl coa, a substrate for de novo lipogenesis (dnl) and an inhibitor of mitochondrial fatty acid β-oxidation (fao). malonyl coa is also a substrate for microsomal fatty acid elongation, an important pathway for saturated (sfa), mono- (mufa) and polyunsaturated fatty acid (pufa) synthesis. despite the interest in acc as a target for obesity and cancer therapy, little attention has been given to the role acc plays in long chain fatty acid synthes ... | 2011 | 21184748 |
| soraphen a, an inhibitor of acetyl coa carboxylase activity, interferes with fatty acid elongation. | acetyl coa carboxylase (acc1 and acc2) generates malonyl coa, a substrate for de novo lipogenesis (dnl) and an inhibitor of mitochondrial fatty acid β-oxidation (fao). malonyl coa is also a substrate for microsomal fatty acid elongation, an important pathway for saturated (sfa), mono- (mufa) and polyunsaturated fatty acid (pufa) synthesis. despite the interest in acc as a target for obesity and cancer therapy, little attention has been given to the role acc plays in long chain fatty acid synthes ... | 2011 | 21184748 |