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Treatment of pi-allyltricarbonyliron lactone complexes bearing an adjacent leaving group, with lithium naphthalenide causes decomplexation to acyclic dienols in excellent yield and without any scrambling of the allylic centre.
A graphite felt electrode modified with (6S,7R,10R)-4-amino-2,2,7-trimethyl-10-isopropyl-1-azaspiro[5.5]undecane N-oxyl was prepared for electrocatalytic oxidation of diols; electrolysis of diols on the modified electrode yielded optically active lactones (92.0-96.4%), with an enantiopurity of 82-99% ee.
A novel approach to chiral succinimides and derived compounds has been developed that involves chiral lithium amide desymmetrisation of an N-ortho-tert-butylphenyl succinimide to generate a putative atropisomeric intermediate enolate, alkylation of which enables access to the lignan lactone (+)-hinokinin.
Parallel solution-phase synthesis of sulfide AHL analogues (10a-s) by one-pot or a sequential approach is reported. The corresponding sulfoxides 13a-e and sulfones 14a-e were prepared to expand the diversity of the 19-member array of sulfides . Likewise, dithianes 12a-c were prepared with similarity both to sulfides 10a-s and to bioactive structures from garlic. Design and biological screening of all compounds presented in this work targeted inhibition of quorum-sensing comprising competitive inhibition of transcriptional regulators LuxR and LasR. The design was based on critical interactions within the binding-site and structural motifs in molecular components isolated from garlic, 7 and 8, shown to be quorum-sensing inhibitors but not antibiotics. A potent quorum-sensing inhibitor N-(heptylsulfanylacetyl)-l-homoserine lactone (10c) was identified. Together with data collected for the other analogues, the resulting structure-activity relationship led to a hypothesis in which competitive binding was assumed.
Exposure of cyclic alkenes bearing a carboxylic acid and a malonate group to manganese(III) acetate and an appropriate copper(II) salt provides the corresponding tricyclic gamma-lactones in good yield.
1. The incorporation of dl-[2-(14)C]mevalonic acid lactone into beta-carotene and the phytol side chain of chlorophyll has been investigated in cotyledons of four species of pine seedlings (Pinus silvestris, P. contorta, P. radiata and P. jeffrei) grown in darkness and in light. 2. The relative incorporation of label into beta-carotene and the phytol side chain of chlorophyll is similar to that observed in experiments on monocotyledons and dicotyledons. 3. The relative incorporation of (14)CO(2) into beta-carotene and phytol is much higher than the incorporation of [2-(14)C]mevalonic acid.
(23S)-23,25-Dihydroxycholecalciferol was converted into at least five metabolites in kidney homogenates prepared from 1,25-dihydroxycholecalciferol-treated chickens. One of these has been positively identified as 23,25,26-trihydroxycholecalciferol by u.v.-absorbance analysis, mass spectrometry and chemical formation of derivatives. 23,25,26-Trihydroxycholecaciferol produces 25-hydroxycholecalciferol-26,23-lactone when incubated in chick kidney homogenates.
A pseudomonad was separated having a pantothenase that produced beta-alanine and pantoic acid. The pantothenase from an old strain, Pseudomonas fluorescens UK-1, was shown to produce beta-alanine and pantoyl lactone. The pantoic acid-producing pantothenase was characterized and compared with the pantothenase from the strain UK-1. The Mr was 240,000; it apparently consists of four subunits. The Km value for pantothenate is 3 mM. The enzymic activity is affected by an ionizable group of pK 8.4, the enzyme is active at higher pH, and V but not Km is affected by pH. This pantothenase is not inhibited by di-isopropyl phosphorofluoridate or phenylmethanesulphonyl fluoride, unlike the enzyme from the strain UK-1. Both pantothenases are inhibited by m-aminophenylboronic acid, oxalate, oxaloacetate and Cl- ions. The pantoic acid-producing pantothenase is inhibited also by SO4(2-) ions. The strong inhibitions by many compounds make this pantothenase unsuitable for the assay of pantothenic acid.
We report the development of a new spectrophotometric assay for 6-phosphogluconolactonase. The labile substrate 6-phosphoglucono-delta-lactone is prepared from glucose 6-phosphate by enzymes co-immobilized on Sepharose beads. The assay has the advantages of high sensitivity for routine determination of enzyme activity and allows determination of both Km and Vmax. from a single assay. A method for estimating the contribution of spontaneous hydrolysis to total hydrolysis is described. This assay overcomes the problems encountered with all previous assays.
Vitamin C deficient pigs, when fed a diet lacking L-ascorbic acid (AscA), manifest deformity of the legs, multiple fractures, osteoporosis, growth retardation and haemorrhagic tendencies. This trait was shown by others to be controlled by a single autosomal recessive allele designated as od (osteogenic disorder). The inability of AscA biosynthesis in primates and guinea pigs that exhibit similar symptoms, when they are not supplemented with AscA in the food, was traced to the lack of L-gulono-gamma-lactone oxidase, which catalyzes the terminal step in the biosynthesis of AscA. The non-functional GULOP was mapped to human chromosome 8p21 that corresponds to an evolutionarily conserved segment on either porcine chromosome 4 (SSC4) or 14 (SSC14). We investigated linkage between OD and SSC4- and 14-specific microsatellite loci in order to map the OD locus. Twenty-seven informative meioses in families from one sire and three dams revealed linkage of od with microsatellites SW857 and S0089, located in the subcentromeric region of SSC14. We isolated part of the GULO gene of the pig by screening a porcine genomic library using a pig GULO cDNA as a probe, and mapped it to SSC14q14 by fluorescence in situ hybridization (FISH). Thus, the porcine GULO gene is both a good physiological and positional candidate gene for vitamin C deficiency in pigs.
Many bacteria sense an appropriate growth condition or a critical population density for gene expression by producing acylhomoserine lactones (acyl-HSLs) that act as intercellular autoinduction signals. We recently showed that, in Ralstonia (Pseudomonas) solanacearum, a phytopathogenic bacterium, acyl-HSL production requires soll, which encodes a putative acyl-HSL synthase, and that its expression is positively regulated by the acyl-HSL-responsive SolR transcriptional regulator. This acyl-HSL-dependent autoinduction system is noteworthy because (i) it is regulated by a 'higher level' autoinducer system (responsive to 3-hydroxypalmitic acid methyl ester) via PhcA, a LysR-type transcriptional regulator and (ii) acyl-HSL production requires two additional unlinked loci. As reported here, cloning and sequencing of one of these other loci revealed that it encodes a homologue of RpoS, an alternative sigma factor (sigmaS) that in other bacteria activates gene expression during stationary phase or in response to stress conditions. R. solanacearum RpoS (RpoS(Rso)) was demonstrated to function as a sigma factor because when introduced in trans into an Escherichia coli rpoS mutant it largely restored expression of the RpoS-dependent bolAp1 gene. Mutation of rpoS(Rso) in R. solanacearum reduced survival during starvation and low pH conditions, but did not affect survival during exposure to hydrogen peroxide, high osmolarity or high temperature. This mutant was also altered in its production of several virulence factors and wilted tomato plants several days more slowly than the wild-type parent. Transcription of solR and soll were decreased in an rpoS(Rso) background (thereby reducing acyl-HSL production), but neither mutations in solR, soll or phcA nor addition of acyl-HSLs affected rpoS(Rso) expression. Therefore, in R. solanacearum the acyl-HSL-dependent autoinduction system is controlled both by a second autoinduction system and by the RpoS(Rso) sigma factor.
In higher plants, the terminal step of L-ascorbic acid (AsA) biosynthesis is catalyzed by the enzyme L-galactono-1,4-lactone dehydrogenase (EC 1.3.2.3, GalLDH). We generated AsA-deficient transgenic tobacco BY-2 cell lines by antisense expression of the GalLDH cDNA that was amplified from BY-2 cells using PCR. Two transgenic cell-lines, AS1-1 and AS2-2, having a marked expression of antisense RNA were analyzed. Antisense suppression of GalLDH mRNA led to a significant decline in the GalLDH activity. The AsA levels in the transgenic cell lines were found to be 30% lower than the wild-type BY-2 cells. In synchronous cultures, division of AS1-1 and AS2-2 cells was restrained with a concomitant decrease in mitotic index that was probably due to a decline in AsA levels. The rate of cell growth was also found to be less than that of the wild-type cells. Interestingly, there was a significant phenotypic difference between the transgenic and wild-type cells. The calli of AS1-1 and AS2-2 appeared to be sticky and soft. Back extrusion method also showed that AsA-deficient BY-2 callus was rheologically soft. Furthermore, microscopic analysis revealed that AS1-1 and AS2-2 cells were abnormally slender, suggesting a potential for a significant and a uni-axial elongation. Thus, we observed that decline in the AsA levels has an adverse effect on the division, growth and structure of a plant cell.
Toxins from three Bacillus licheniformis strains connected to a fatal food poisoning were isolated and their structures elucidated. Toxins were purified from methanol extracts of the B. licheniformis biomass using boar sperm cells as the toxicity indicator. The HPLC purified toxins showed protonated masses m/z 1007, 1021 and 1035 in MALDI-TOF-MS. The toxins isolated from the strains of different origins contained the same three components of which and each had a same amino-acid residues L-Gln, L-Leu, D-Leu, L-Val, L-Asp, D-Leu and L-Ile in that order. Toxins were identified as lichenysin A, a cyclic lactonic heptalipopeptide in which the main 3-hydroxy fatty acids are 13-15 carbons in length. We showed that the toxins from food and food poisoning isolates of B. licheniformis were identical to lichenysin A both in the structure and in the toxic symptoms induced to boar spermatozoa. Confocal laser scanning microscopy showed that the acrosome and the plasma membrane of boar spermatozoa were the targets of lichenysin A toxicity.
The purpose of this study was to investigate the production of N-acyl-homoserine lactone (AHL) signal molecules in ocular gram-negative bacteria. A total of 91 ocular strains isolated from contact lens adverse response patients and asymptomatic subjects were used in the study. These included Acinetobacter, Aeromonas hydrophila, Escherichia coli, Haemophilus influenzae, Klebsiella oxytoca, Pseudomonas aeruginosa, Serratia liquefaciens, Serratia marcescens, and Stenotrophomonas maltophilia. The biosensor strains Chromobacterium violaceum mutant CV026 and Agrobacterium tumefaciens A136 were used for detection of AHL signal molecules. The majority of A. hydrophila, P. aeruginosa, and S. liquefaciens strains produced more than one AHL molecule. Serratia marcescens strains were AHL positive only under detection of A136. The rest of the test species did not show any AHL production under the current detection system. These findings indicate that AHL-mediated quorum-sensing systems are present in some of the ocular bacteria, and the different signal molecules may be involved with the quorum-sensing pathway in the other bacterial species.
The soft-rotting bacterium, Erwinia carotovora ssp. carotovora (E. c. carotovora), produces an array of extracellular enzymes (= exoenzymes), including pectate lyase (Pel), polygalacturonase (Peh), cellulase (Cel) and protease (Prt), as well as HarpinEcc, the elicitor of hypersensitive reaction (HR). The production of these exoenzymes and HarpinEcc responds to plant products and the quorum-sensing signal [N-(3-oxohexanoyl)-L-homoserine lactone; OHL] and is subject to both transcriptional and post-transcriptional regulation. hexA of E. c. carotovora strain Ecc71 (hereafter hexA71), like that of another E. c. carotovora strain, negatively controls the production of exoenzymes, OHL and virulence in E. c. carotovora strain Ecc71. In addition to exoenzymes, HexA71 negatively regulates the expression of hrpNEcc, the structural gene for HarpinEcc. Exoenzyme overproduction is abolished by OHL deficiency in a HexA- and Ohll- double mutant, indicating that HexA and OHL are components of a common regulatory pathway controlling exoenzyme production. HexA71 negatively affects RpoS, as the levels of this alternative sigma factor are higher in the HexA- mutant than in the HexA+ strain. However, a HexA- and RpoS double mutant produces higher levels of exoenzymes and transcripts of pel-1, peh-1 and celVgenes than the HexA- and RpoS+ parent. Thus, the elevated levels of RpoS protein in the HexA- mutant do not account for exoenzyme overproduction. The following evidence associates for the first time the phenotypic changes in the HexA mutant to overproduction of rsmB RNA, a global regulator of exoenzymes, HarpinEcc, OHL and secondary metabolites. Analyses of rsmB transcripts and expression of an rsmB-lacZoperon fusion in E. c. carotovora strain Ecc71 revealed that HexA71 negatively regulates transcription of rsmB. Multiple copies of hexA71+ DNA suppress various phenotypes, including exoenzyme production in E. c. carotovora strain Ecc71, and concomitantly inhibit the production of rsmB, pel-1, peh-1, celV and hrpNEcc transcripts. Multiple copies of rsmB+ DNA, on the other hand, stimulate exoenzyme production by relieving the negative effects of a chromosomal copy of hexA+. The occurrence of hexA homologues and the negative effect of the dosage of hexA71 DNA on rsmB transcripts were also detected in other E. c. carotovora strains as well as Erwinia carotovora atroseptica and Erwinia carotovora betavasculorum. Extrapolating from the findings with LrhA, the Escherichia coli homologue of HexA, and the presence of sprE homologues in E. carotovora subspecies, we propose that HexA71 controls several regulatory pathways in E. carotovora including rsmB transcription and the production of SprEEcc which, in turn, affects RpoS levels. A model is presented that integrates the findings presented here and our current knowledge of the major regulatory network that controls exoprotein production in soft-rotting Erwinia carotovora subspecies.
The present study was to examine whether andrographolide, a diterpenoid lactone isolated from the anti-inflammatory herbal medicine Andrographis paniculata (Burm. f.) Nees. (Acanthaceae), has the ability to prevent phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion by rat neutrophils. Results demonstrated that PMA (100 ng/ml) induced rapid accumulation of H2O2 and O2. in neutrophils within 30 minutes. Andrographolide (0.1 to 10 microM) pretreatment (10 min, 37 degrees C) significantly attenuated the accumulation of these two oxygen radical metabolites. Administration of andrographolide also significantly prevented fMLP-induced neutrophil adhesion. These data suggest that preventing ROS production and neutrophils adhesion may confer andrographolide the ability to be an anti-inflammatory drug.
The leishmanicidal compounds isolated from whole plants of Elephantopus mollis H.B.K. were identified as follows. Three new sesquiterpenoid lactones, 2,5-epoxy-2beta-hydroxy-8alpha-(2-methylpropenoyloxy)-4(15),10(14),11(13)-germacratrien-12,6alpha-olide, (4betaH)-8alpha-(2-methylpropenoyloxy)-2-oxo-1(5),10(14), 11(13)-guaiatrien-12,6alpha-olide and (4betaH)-5alpha-hydroxy-8alpha-(2-methylpropenoyloxy)-1(10),11(13)-guaiadiene-12,6alpha-olide, were isolated from Peruvian and Brazilian collections together with four known sesquiterpenoids, molephantin, elephantopin, isoelephantopin and 2-deethoxy-2beta-methoxyphantomolin. They exhibited potent in vitro leishmanicidal activities against Leishmania major. The alpha-methylene-gamma-butyrolactone moiety was found to be essential to the potent leishmanicidal effect observed.
Artemisinin 1, dihydro-epideoxyarteannuin B 2 and deoxyartemisinin 3 were isolated from the sequiterpene lactone-enriched fraction obtained from the crude ethanolic extract of Artemisia annua L. These compounds were tested on ethanol and indomethacin-induced ulcer models. Compound 1 did not afford cytoprotection under the experimental models tested. Only compounds 2 and 3 decreased the ulcerative lesion index produced by ethanol and indomethacin in rats. These compounds did not demonstrate antiulcerogenic activity when tested on the ethanol-induced ulcer model, with previous administration of indomethacin, suggesting that the antiulcerogenic activity is a consequence of prostaglandin synthesis increase.