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At least 1,423 records · Page 79Linked to original sources
PubMed1999

Cloning and characterisation of the rpoS gene from plant growth-promoting Pseudomonas putida WCS358: RpoS is not involved in siderophore and homoserine lactone production.

The rpoS gene which encodes a stationary phase sigma factor has been identified and characterised from the rhizosphere-colonising plant growth-promoting Pseudomonas putida strain WCS358. The predicted protein sequence has extensive homologies with the RpoS proteins form other bacteria, in particular with the RpoS sigma factors of the fluorescent pseudomonads. A genomic transposon insertion in the rpoS gene was constructed, these mutants were analysed for their ability to produce siderophore (iron-transport agent) and the autoinducer quorum-sensing molecules called homoserine lactones (AHL). It was determined that RpoS was not involved in the regulation of siderophore and AHL production, synthesis of these molecules is important for gene expression at stationary phase. P. putida WCS358 produces at least three different AHL molecules.

4-Butyrolactone↗
PubMed2001

Tests to determine LC50 and discriminating doses for macrocyclic lactones against the cattle tick, Boophilus microplus.

Laboratory tests were carried out on larvae and adults of the cattle tick Boophilus microplus to determine the toxicity of macrocyclic lactone acaricides (MLs). Technical and commercial MLs were used in larval packet test (LPT), larval immersion test (LIT) and adult immersion test (AIT). In LIT and AIT the toxicity of MLs was much higher than for LPT. In the AIT, diluting the injectable formulation of MLs in water was as effective as dilution in ethanol+Triton X-100. LC50, LC99.9 and 95% confidence limits were determined so that a discriminating dose (DD) could be set for larval and adult tests in order to diagnose potential resistance to MLs in field samples of the tick. These DDs are for Australian strains of B. microplus and may not be suitable for other strains until further work is carried out. The value of these diagnostic tests can only be verified if or when resistance to MLs emerges in ticks.

Animals↗
PubMed2002

Resistance to therapeutic treatment with macrocyclic lactone anthelmintics in Ostertagia circumcincta.

Eighty-eight lambs were allocated to one of four groups which were then dosed with 10,000 infective-stage larvae (L3) of one of four populations of Ostertagia circumcincta; the first (S) was an isolate known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant isolate which had been recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection. The third (R) was derived from OR but had been passaged for five generations in the laboratory with each generation being screened with all three broad-spectrum drench families; the fourth (R x S) was an F1 cross between the S and R isolates. On patency, each of the four infection groups was sub-divided into five treatment groups, one of which received no anthelmintic while the others were administered either oral ivermectin (IVM-oral), controlled-release capsules containing ivermectin (IVM-CRCs), oral moxidectin (MOX-oral) or injectable MOX (MOX-inj). Neither formulation of IVM reduced FEC in the R, R x S and OR infected lambs compared to their untreated controls, but significant reductions were observed in all cases following MOX-oral or MOX-inj treatment. Similarly, neither IVM formulation significantly reduced the numbers of R or R x S worms compared to their untreated controls, although the numbers of OR worms were reduced in both cases (P<0.05). Direct comparisons of efficacy across the isolates, however, indicated that neither formulation was any more effective against R x S or OR worms than against the more highly selected R worms. In contrast, both MOX formulations significantly reduced worm numbers of all the resistant isolates compared to their respective untreated controls; furthermore, worm burdens of R x S were reduced significantly more than burdens of R (P<0.05). Reductions in OR burdens, which were intermediate between the two, did not differ significantly from either. The results are consistent with published work on Haemonchus contortus, which suggests that macrocyclic lactone (ML) resistance is expressed as a dominant trait under treatment with IVM. However, these data differ from the H. contortus studies in suggesting that ML resistance in O. circumcincta may effectively be rendered incompletely dominant or recessive by treatment with MOX.

Administration, Oral↗
PubMed2003

Resistance to prophylactic treatment with macrocyclic lactone anthelmintics in Teladorsagia circumcincta.

Sixty-four Romney ewe lambs were allocated to 12 groups on the basis of liveweight. Four groups (n=5) were administered oral ivermectin (IVM), 4 (n=6) oral moxidectin (MOX) and the remaining 4 (n=5) controlled-release capsules containing IVM (IVM-CRCs). Nine and 10 days later, the groups within each treatment type were challenged with infective-stage larvae (L3) of 1 of 4 different isolates of Teladorsagia circumcincta (two doses each of 5000 L3). The first of these (S) was known to be anthelmintic-susceptible; the second (OR) was a multiple anthelmintic-resistant strain recovered from the field following therapeutic failure of both ivermectin and moxidectin and subsequently maintained in the laboratory without further anthelmintic selection; the third (R) was derived from OR but had been passaged for five generations indoors with each generation being screened with all three broad-spectrum anthelmintic classes; and the fourth (RxS) was an F1 cross between the R and S isolates. As anticipated, because of its limited residual activity, IVM had no significant effect on the establishment, 9 and 10 days post-treatment, of any of the parasite isolates. In contrast MOX, which has greater residual activity, was highly effective at preventing the establishment of the S isolate but showed no significant effect against the OR, R or RxS isolates. The IVM-CRC was also highly effective at preventing the establishment of the S isolate and furthermore it significantly reduced establishment of both the OR and RxS isolates, although it had no significant effect against the R isolate. The results suggest that with respect to the establishment of T. circumcincta L3s following anthelmintic treatment, macrocyclic lactone (ML) resistance is effectively a dominant trait in the presence of MOX, while it behaves as a partially dominant/recessive trait under treatment with IVM-CRCs. The potential implications of this finding in relation to selection for ML resistance in T. circumcincta are discussed.

Abomasum↗
PubMed2001

Sesquiterpene lactones from Centaurea tweediei.

Aerial parts of Centaurea tweediei from Argentina afforded as the main constituent the sesquiterpene lactone onopordopicrin and minor amounts of a new heliangolide, a new guaianolide, a new eudesmanolide, a new eudesmane acid and the lignans arctigenin and matairesinol.

Journal Article↗
PubMed1999

Lucidenic acid O and lactone, new terpene inhibitors of eukaryotic DNA polymerases from a basidiomycete, Ganoderma lucidum.

Terpenoids, 1, 2 and 3, which selectively inhibit eukaryotic DNA polymerase activities, were isolated from the fruiting body of a basidiomycete, Ganoderma lucidum, and their structures were determined by spectroscopic analyses. New terpenes, lucidenic acid O (1) and lucidenic lactone (2), prevented not only the activities of calf DNA polymerase alpha and rat DNA polymerase beta, but also these of human immunodeficiency virus type 1 reverse transcriptase. Cerevisterol (3), which was reported to be a cytotoxic steroid, inhibited only the activity of DNA polymerase alpha. Although these compounds did not influence the activities of prokaryotic DNA polymerases and other DNA metabolic enzymes such as T7 RNA polymerase and deoxyribonuclease I.

Animals↗
PubMed2002

Parthenin, a sesquiterpene lactone of Parthenium hysterophorus L. is a high toxicity clastogen.

The in vitro and in vivo genotoxicity of parthenin, a sesquiterpene lactone from Parthenium hysterophorus L. with allergenic and irritant action, was assessed in three short-term tests: bacterial reversion in Salmonella typhimurium and Escherichia coli, in vitro chromosomal aberrations in peripheral blood lymphocytes and micronuclei in mouse peripheral blood. Parthenin was not mutagenic in S. typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 but a weak response was observed in TA 102 (+S9) from 0.19 to 1.22 micromole per plate. Concentrations of 7.62 micromole per plate or higher were toxic, but the effect was reduced when S9 was present. Screening of oxidative mutagenesis with E. coli strains IC 188 and IC 203 gave negative results. Parthenin induced chromosomal aberrations, mainly chromatid breaks, in blood lymphocytes exposed to 10-60 microM during 20 h. An association was found with cytotoxicity, since concomitant nuclear alterations such as pycnosis, micronuclei and karyorrhexis were observed. Sister chromatid exchanges (SCEs) in lymphocytes were not influenced by exposure to parthenin; rather a decrease was observed at 60 microM. On the other hand, a minor increment in polyploid metaphases was found at 40 microM. When a single intraperitoneal (i.p.) dose of 4-31 mg/kg of parthenin was administered to mice, a positive increase in the micronucleated reticulocyte (RET) frequency was observed at 48 h for both sexes at the highest dose.

Allergens↗
PubMed2002

Effects of macrocyclic lactone anthelmintics on feeding and pharyngeal pumping in Trichostrongylus colubriformis in vitro.

The effects of macrocyclic lactone anthelmintics (MLs) on feeding by Trichostrongylus colubriformis nematodes in vitro were examined using inulin uptake as a measure of ingestion and electropharyngeograms as a record of the electrical events associated with pharyngeal pumping. Inulin uptake was inhibited by the 4 MLs tested (EC50s 0.045-4.57 nM), with an order of potency of eprinomectin (most potent), ivermectin, ivermectin monosaccharide, and ivermectin aglycone. The MLs caused both the frequency and amplitude of pharyngeal electrical events to decrease. In individual worms the inhibition of pump frequency preceded the inhibition of pump amplitude. The order of potency of the MLs as inhibitors of frequency was ivermectin aglycone, ivermectin, ivermectin monosaccharide and eprinomectin. The difference compared with the inulin assay results are probably due to the dynamics of drug uptake in the two systems. It was possible that the nematodes in the electrophysiology experiments were effectively orally ligated by enclosure of the worm's head in the recording pipette which contained no drug. Despite this difference in relative potencies, both the ingestion assays and the electrical events indicate that MLs are potent inhibitors of the pharynx in T. colubriformis in vitro. The sequence of effects on pharyngeal electrical activity suggests that ML action involves an initial inhibitory effect on the rate of pharyngeal contractions, followed by a decrease in the amplitude of the potentials associated with pharyngeal pumping events.

Animals↗
PubMed1988

Channels at the catalytic site of glycogen phosphorylase b: binding and kinetic studies with the beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone N-phenylurethane.

Regions of low packing density in the vicinity of the catalytic site of glycogen phosphorylase b are described with the aid of a computer program that generates a contour map in which the contour level is inversely proportional to the packing density in the protein. It is shown that, although there is no direct route from the catalytic site to the surface, there are two possible channels that could allow access for substrates following conformational changes in the enzyme. The first channel, channel 1, leads from the catalytic site to the surface close to the nucleoside inhibitor site and requires movements of residues 280-285 and Arg 569 in order to obtain access. Previous crystallographic experiments have shown that in the presence of substrates or R-state inhibitors these parts of the polypeptide chain undergo large conformational changes. The properties of the second channel (channel 2), which is the more extensive channel, have been investigated with the potent beta-glycosidase inhibitor D-gluconohydroximo-1,5-lactone N-phenylurethane (PUG). Crystallographic binding studies at 2.4-A resolution show that the compound binds neatly at the catalytic site of phosphorylase b. The glucopyranosylidene ring, in the half-chair conformation, occupies a similar but not identical position (shift about 0.6 A) to that occupied by other glucosyl compounds bound at the catalytic site.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Structure-function relationships in glucagon: properties of highly purified des-His-1-, monoiodo-, and (des-Asn-28, Thr-29)(homoserine lactone-27)-glucagon.

We have compared the ability of glucagon and three highly purified derivatives of the hormone to activate hepatic adenylate cyclase (an expression of biological activity of the hormone) and to compete with [125]glucagon for binding to sites specific for glucagon in hepatic plasma membranes. Relative to that of glucagon, biological activity and affinity of [des-Asn-28,Thr-29](homoserine lactone-27)-glucagon, prepared by CNBr treatment of glucagon, were reduced equally by 40- to 50-fold. By contrast, des-His-1-glucagon, prepared by an insoluble Edman reagent and highly purified (less than 0.5% contamination with native glucagon), displayed a 15-fold decrease in affinity but a 50-fold decrease in biological activity relative to that of the native hormone. At maximal stimulating concentrations, des-His-1-glucagon yielded 70% of the activity given by saturating concentrations of glucagon. Thus, des-His-1-glucagon can be classified as a partial weak agonist. Highly purified monoiodoglucagon and native glucagon displayed identical biological activity and affinity for the binding sites. Our findings suggest that the hydrophilic residues at the terminus of the carboxy region of glucagon are involved in the process of recognition at the glucagon receptor but do not participate in the sequence of events leading to activation of adenylate cyclase. The amino-terminal histidyl residue in glucagon plays an important but not obligatory role in the expression of hormone action and contributes to a significant extent in the recognition process.

Adenylyl Cyclases↗
PubMed2004

Crystal structure of 3-carboxy-cis,cis-muconate lactonizing enzyme from Pseudomonas putida, a fumarase class II type cycloisomerase: enzyme evolution in parallel pathways.

3-Carboxy-cis,cis-muconate lactonizing enzymes (CMLEs), the key enzymes in the protocatechuate branch of the beta-ketoadipate pathway in microorganisms, catalyze the conversion of 3-carboxy-cis,cis-muconate to muconolactones. We have determined the crystal structure of the prokaryotic Pseudomonas putida CMLE (PpCMLE) at 2.6 A resolution. PpCMLE is a homotetramer and belongs to the fumarase class II superfamily. The active site of PpCMLE is formed largely by three regions, which are moderately conserved in the fumarase class II superfamily, from three respective monomers. It has been proposed that residue His141, which is highly conserved in all fumarase class II enzymes and forms a charge relay with residue Glu275 (both His141 and Glu275 are in adenylosuccinate lyase numbering), acts as the general base in most fumarase class II superfamily members. However, this charge relay pair is broken in PpCMLE. The residues corresponding to His141 and Glu275 are Trp153 and Ala289, respectively, in PpCMLE. The structures of prokaryotic MLEs and that of CMLE from the eukaryotic Neurospora crassa are completely different from that of PpCMLE, indicating MLEs and CMLEs, as well as the prokaryotic and eukaryotic CMLEs, evolved from distinct ancestors, although they catalyze similar reactions. The structural differences may be related to recognition by substrates and to differences in the mechanistic pathways by which these enzymes catalyze their respective reactions.

Amino Acid Sequence↗
PubMed2006

A bromoenol lactone suicide substrate inactivates group VIA phospholipase A2 by generating a diffusible bromomethyl keto acid that alkylates cysteine thiols.

Phospholipases A2 (PLA2) comprise a superfamily of enzymes that hydrolyze phospholipids to a free fatty acid, e.g., arachidonate, and a 2-lysophospholipid. Dissecting their individual functions has relied in large part on pharmacological inhibitors that discriminate among PLA2. Group VIA PLA2 (iPLA2beta) has a GTSTG serine lipase consensus sequence, and studies with a bromoenol lactone (BEL) suicide substrate inhibitor have been taken to suggest that iPLA2beta participates in a wide variety of biological processes. Such conclusions presume inhibitor specificity. Inhibition by BEL requires its hydrolysis by and results in uncharacterized covalent modification(s) of iPLA2beta. We performed mass spectrometric analyses of proteolytic digests of BEL-treated iPLA2beta to identify modifications associated with loss of activity. The GTSTG active site and large flanking regions of sequence are not modified by BEL treatment, but most iPLA2beta Cys residues are alkylated at various BEL concentrations to form a thioether linkage to a BEL keto acid hydrolysis product. Synthetic Cys-containing peptides are alkylated when incubated with iPLA2beta and BEL, which reflects iPLA2beta-catalyzed BEL hydrolysis to a diffusible bromomethyl keto acid product that reacts with distant thiols. The BEL concentration dependence of Cys651 alkylation closely parallels that of loss of iPLA2beta activity. No amino acid residues other than Cys were found to be modified, suggesting that Cys alkylation is the covalent modification of iPLA2beta responsible for loss of activity, and the alkylating species appears to be a diffusible hydrolysis product of BEL rather than a tethered acyl-enzyme intermediate.

Amino Acid Sequence↗
PubMed1999

The Effect of Rapeseed Oil Uptake on the Production of Erythromycin and Triketide Lactone by Saccharopolyspora erythraea.

Saccharopolyspora erythraea was grown in an oil-based process medium at two different laboratory scales. The initial concentration of rapeseed oil in the medium was shown not to affect the growth, while addition of oil significantly increased erythromycin A production. Increasing the agitation speed at the 2 L scale increased the growth of the culture and the production of erythromycin A but had little effect on the level of oil remaining in the fermentation. Maximum oil utilization of 50% (w/w) was obtained in both 2 and 7 L cultures. Gas chromatography analysis of the process medium showed that there was no accumulation of fatty acids and glycerides during the fermentations. The specific oil utilization by the recombinant strain of S. erythraea was significantly lower compared to the wild-type strain grown at the same scale and initial oil concentration; the recombinant strain also produced lower concentrations of the novel polyketide, triketide lactone.

Journal Article↗
PubMed2002

Novel isomerically pure tetrasubstituted allylboronates: stereocontrolled synthesis of alpha-exomethylene gamma-lactones as aldol-like adducts with a stereogenic quaternary carbon center.

In spite of their inherent isomerization tendency and low reactivity, 1-alkoxycarbonyl vinylcopper(I) intermediates from the conjugate addition of organocuprates onto acetylenic esters were trapped with very high cis-addition selectivity with iodomethylboronic esters in the presence of HMPA. The resulting isomerically pure 3,3-disubstituted allylboronates react with aldehydes in a highly diastereo- and enantioselective manner, providing alpha-exomethylene gamma-lactones with a stereogenic quaternary beta-carbon center.

Journal Article↗
PubMed2004

Rational pathway engineering of type I fatty acid synthase allows the biosynthesis of triacetic acid lactone from D-glucose in vivo.

Metabolic pathway engineering is a powerful tool to synthesize structurally diverse and complex chemicals via genetic manipulation of multistep catalytic systems involved in cell metabolism. Here, we report the rational design of a fatty acid biosynthetic pathway, Brevibacterium ammoniagenes fatty acid synthase B (FAS-B), that allows the microbial synthesis of triacetic acid lactone (TAL) from an inexpensive feedstock, d-glucose. TAL can be chemically converted to phloroglucinol, which is a core structure for the synthesis of various high value bioactive compounds and energetic compounds such as 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Synthesis of phloroglucinol from d-glucose using this combined biological and chemical synthesis may offer significant advantages over the current phloroglucinol manufacture, including environmental friendliness and reduction in the cost of phloroglucinol. More importantly, it represents a novel strategy for the benzene-free synthesis of aromatic chemicals.

Bacterial Proteins↗
PubMed2003

A GaCl3-catalyzed [4+1] cycloaddition of alpha,beta-unsaturated carbonyl compounds and isocyanides leading to unsaturated gamma-lactone derivatives.

A GaCl3-catalyzed reaction of alpha,beta-unsaturated ketones with isocyanides leading to the formation of unsaturated lactone derivatives is described. This is the first example of the catalytic [4+1] cycloaddition of alpha,beta-unsaturated ketones and isocyanides. GaCl3 is an excellent catalyst due to its lower oxophilicity, which is desirable for all of the key steps, such as E/Z isomerization, cyclization, and deattachment from the products.

Journal Article↗