共查询到20条相似文献,搜索用时 31 毫秒
1.
Yang B Liu Z Deng B Zeng Y Hu J Li W Hu Z 《The Journal of General and Applied Microbiology》2011,57(6):379-386
Microorganisms able to bioconvert DL-2-amino-Δ(2)-thiazoline-4-carboxylic acid (DL-ATC) into L-cysteine were originally isolated from 10 soil samples with DL-ATC as the sole nitrogen source. Ninety-seven L-cysteine-producing bacterial strains were screened out and obtained in pure culture. Among them, a strain, designated as HUT-78, was selected as the best producer, with a molar bioconversion rate of 60%. Based on the 16S rRNA gene sequence analysis, this isolate was placed within the genus Pseudomonas. A novel mutant of this strain with a significantly reduced activity of L-cysteine desulfhydrase, a L-cysteine-decomposing enzyme, was derived by UV-mutagenesis. This mutant, designated as mHUT-78, exhibited a 42% increase in L-cysteine producing activity. Moreover, the bioconversion reactions in both the parent and the mutant strain were significantly accelerated by co-overexpression of the two key enzymes, AtcB and AtcC, involved in the bioconversion reaction. 相似文献
2.
l-2-Amino-Δ2-thiazoline-4-carboxylic acid hydrolase (ATC hydrolase) was purified and characterized from the crude extract of Escherichia coli, in which the gene for ATC hydrolase of Pseudomonas sp. strain ON-4a was expressed. The results of SDS–polyacrylamide gel electrophoresis and gel filtration on Sephacryl S-200 suggested that the ATC hydrolase was a tetrameric enzyme consisted of identical 25-kDa subunits. The optimum pH and temperature of the enzyme activity were pH 7.0 and 30–35°C, respectively. The enzyme did not require divalent cations for the expression of the activity, and Cu2+ and Mn2+ ions strongly inhibited the enzyme activity. An inhibition experiment by diethylpyrocarbonic acid, 2-hydroxy-5-nitrobenzyl bromide, and N-bromosuccinimide suggested that tryptophan, cysteine, or/and histidine residues may be involved in the catalytic site of this enzyme. The enzyme was strictly specific for the l-form of d,l-ATC and exhibited high activity for the hydrolysis of l-ATC with the values of K
m (0.35 mM) and V
max (69.0 U/mg protein). This enzyme could not cleave the ring structure of derivatives of thiazole, thiazoline, and thiazolidine tested, except for d,l- and l-ATC. These results show that the ATC hydrolase is a novel enzyme cleaving the carbon–sulfur bond in a ring structure of l-ATC to produce N-carbamoyl-l-cysteine. 相似文献
3.
《Bioscience, biotechnology, and biochemistry》2013,77(9):2262-2267
Two novel genes (tsB, tsC) involved in the conversion of DL-2-amino-Δ2-thiazoline-4-carboxylic acid (DL-ATC) to L-cysteine through S-carbamyl-L-cysteine (L-SCC) pathway were cloned from the genomic DNA library of Pseudomonas sp. TS1138. The recombinant proteins of these two genes were expressed in Escherichia coli BL21, and their enzymatic activity assays were performed in vitro. It was found that the tsB gene encoded an L-ATC hydrolase, which catalyzed the conversion of L-ATC to L-SCC, while the tsC gene encoded an L-SCC amidohydrolase, which showed the catalytic ability to convert L-SCC to L-cysteine. These results suggest that tsB and tsC play important roles in the L-SCC pathway and L-cysteine biosynthesis in Pseudomonas sp. TS1138, and that they have potential applications in the industrial production of L-cysteine. 相似文献
4.
Sujay Basu Philip Prathipati Sachin Thorat Shariq Ansari Meena Patel Vaibhav Jain Ramana R. Jinugu Sanjay Niranjan Siddhartha De Satyanarayana Reddy 《Bioorganic & medicinal chemistry》2017,25(1):67-74
A series of novel amino-carboxylic based pyrazole as protein tyrosine phosphatase 1B (PTP1B) inhibitors were designed on the basis of structure-based pharmacophore model and molecular docking. Compounds containing different hydrophobic tail (1,2-diphenyl ethanone, oxdiadizole and dibenzyl amines) were synthesized and evaluated in PTP1B enzymatic assay. Structure–activity relationship based optimization resulted in identification of several potent, metabolically stable and cell permeable PTP1B inhibitors. 相似文献
5.
Chizuko Yatome Hiroki Matsufuru Toru Taguchi Toshihiko Ogawa 《Applied microbiology and biotechnology》1993,39(6):778-781
4-Dimethylaminoazobenzene-2-carboxylic acid (DMBC) was utilized as a necessary carbon and nitrogen source by Pseudomonas stutzeri IAM 12097. o-Aminobenzoic acid (o-ABA), N,N-dimethyl-p-phenylenediamine (DMPA) and cathecol were identified as intermediates of DMBC degradation. DMBC was degraded at a concentration below 70 mol dm–3. The ability to utilize DMBC in P. stutzeri was lost spontaneously to some extent. When P. stutzeri was cured of plasmid DNA (approximately 8 MDal) by treatment with mitomycin C, acridine orange, and chloramphenicol, DMBC was not utilized by the resultant strain. These facts suggest that the degradative ability on DMBC in P. stutzeri is controlled by plasmid DNA.
Correspondence to: C. Yatome 相似文献
6.
K. Wakabayashi K. Soga T. Hoson S. Kamisaka H. Yoshimura K. Shibata 《Plant Growth Regulation》2001,33(3):169-173
The effect of two -amino acids, 2-amino-3-cyclopropyl-butanoicacid (ACPBA) and 2-amino-5-chloro-4-pentenoic acid (ACPA) on the growth oflettuce (Lactuca sativa L.) roots was investigated. BothACPBA and ACPA at 10–4 significantly inhibitedgrowth of roots of light-grown seedlings, while they had no effect on hypocotylgrowth. The lengths of cortical cells in the mature region of roots that hadbeen exposed to either compound were significantly shorter than those ofcontrolroots. Treatment with ACPBA and ACPA significantly decreased the mechanicalextensibility of root cell walls prior to the start of inhibition of rootgrowth. On the other hand, these compounds did not decrease the osmoticconcentration of the cell sap in root tissues. These results suggest that ACPBAand ACPA inhibit the cell elongation process of lettuce roots by decreasing themechanical extensibility of cell walls. 相似文献
7.
Yan Lu Zhao Wang Chien-Ming Li Jianjun Chen James T. Dalton Wei Li Duane D. Miller 《Bioorganic & medicinal chemistry》2010,18(2):477-495
A series of (2RS,4R)-2-arylthiazolidine-4-carboxylic acid amide (ATCAA) was synthesized. Antiproliferative activity against melanoma and prostate cancer cells compared with control cells (fibroblast and RH7777, respectively) was evaluated. Compound 3id showed the best selectivity and growth-inhibition activity against three melanoma cell lines (B16-F1, A375, and WM-164). Compounds 15b and 3ac had good selectivity and potency against four prostate cancer cell lines (DU 145, PC-3, LNCaP, and PPC-1). The structure–activity relationship (SAR) of the side chain, the thiazolidine ring, and phenyl substituents is discussed. Cell cycle analysis showed that the percentage of cancer cells undergoing apoptosis (sub-G1 phase) increased after treatment with 1b and 3ad, which also strongly inhibited melanoma colony formation. In vivo studies on nude mice bearing A375 melanoma tumors showed that compound 1b inhibited tumor growth in a dose-dependent manner. At a dose of 10 mg/kg, 1b significantly inhibited melanoma tumor growth and showed higher efficacy than did dacarbazine at 60 mg/kg. 相似文献
8.
The l-amino acid oxidase of Mytilus edulis has been used to oxidize l-lysine on a large scale in the presence of catalase. The alpha-oxo acid derived from lysine cyclizes to a Schiff base, which readily dimerizes. The dimer undergoes spontaneous dehydration and decarboxylation to form 1,2,3,4,5,6,7,8-octahydropyrido[3,2-a]-indolizin-10(4bH)-one. This structure was established by a study of its molecular weight and infrared, nuclear-magnetic-resonance and mass spectra. 相似文献
9.
Kapić S Fajdetić A Koštrun S Cikoš A Paljetak HČ Antolović R Holmes DJ Alihodžić S 《Bioorganic & medicinal chemistry》2011,19(23):7270-7280
A set of novel macrolones containing the flexible C8 basic linker and quinolone 3-(2'-hydroxyethyl)carboxamido group has been prepared and structurally characterized by NMR and IR spectroscopy, mass spectrometry and molecular modeling. The new compounds were evaluated in vitro against a panel of erythromycin-susceptible and erythromycin-resistant Gram-positive and Gram-negative bacterial strains. Compared to azithromycin, most of the compounds exhibited improved in vitro potency against the key respiratory pathogens. 相似文献
10.
The rate limiting enzyme of heme biosynthesis, δ-aminolevulinic acid synthetase (ALA synthetase), and the second enzyme in the heme biosynthetic pathway, δ-aminolevulinic acid dehydrase (ALA dehydrase), were inhibited by the olefinic amino acid L-2-amino-4-methoxy - -3-butenoic acid (AMTB). Administration of AMTB (20 mg/kg; i.p.) to rats inhibited ALA synthetase and ALA dehydrase in control animals and in animals with markedly elevated activity of ALA synthetase which resulted from the administration of 3,5-dicarbethoxy-1,4-dimethyl-collidine (DDC, 200 mg/kg, i.p.) or allylisopropylacetamide (200 mg/kg, s.c.). AMTB also blocked the synthesis of rat hepatic porphyrins and inhibited the increase in the urinary excretion of δ-aminolevulinic acid and porphobilinogen following DDC (150 mg/kg, p.o.) administration. Preincubation of AMTB with liver mitochondria or a soluble fraction of liver decreased the activity of mitochondrial ALA synthetase and soluble ALA dehydrase, respectively. 相似文献
11.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,732(1):155-164
High-performance liquid chromatography with electrospray ionization mass spectrometry was used to determine 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in urine. After basic hydrolysis of conjugates, the compound was extracted using SPEC-PLUS-3ML-C18 solid-phase extraction columns. A deuterium labelled internal standard (d3-THC-COOH) was added prior to hydrolysis. Separation was performed on a reversed-phase Zorbax Eclipse XDB-C8 analytical column (150×3.0 mm I.D.) using a gradient program from 60 to 80% acetonitrile (4 mM formic acid) at a flow-rate of 0.5 ml/min. The compounds were detected by single ion monitoring of m/z 345 and m/z 348 for the protonated molecules [THC-COOH+H]+ and [d3-THC-COOH+H]+, respectively. The precision and accuracy were tested on spiked urine samples in the range 2.5–125 ng/ml. The mean recovery was 95% (n=58), coefficients of variations were 2.2–4.3% and the limit of detection 2 ng/ml. Diagnostic qualifying ions of THC-COOH (m/z 327 and m/z 299) and d3-THC-COOH (m/z 330) were generated using up-front collision-induced dissociation. The relative ion intensities in clinical samples (n=21) were within ±20% deviation compared with standards. Using this tolerance and the presence of the ions m/z 327 and m/z 299 at the correct retention times as the acceptance criteria for identification of THC-COOH positive samples, the limit of detection was 15 ng/ml. The LC–MS method complies with the current recommendations on drugs of abuse testing, in which mass spectrometric detection is emphasized. 相似文献
12.
Joseph C. Besharse 《Neurochemical research》1992,17(1):75-80
Rhythmic photoreceptor metabolism in relationship to light-dark cycles is now thought be regulated through a retinal feed-back mechanism with dopamine serving as a principal signal initiating light-evoked events. In order to test the hypothesis that depolarizing ON-bipolar neurons participate in the retinal signalling pathway, we determined the effects of L-2-amino-4-phosphonobutyrate (L-APB) on light-evoked cone contraction in eye cups fromXenopus laevis. L-APB blocked the response stereospecifically when applied over a broad concentration range. The high specificity of L-APB in retina suggests that sign-inverting bipolar neurons which depolarize in light are in the signalling pathway. One possibility is that this pathway conveys signals that regulate dopamine release.Special issue dedicated to Dr. Frederick E. Samson. 相似文献
13.
Cociorva OM Li B Nomanbhoy T Li Q Nakamura A Nakamura K Nomura M Okada K Seto S Yumoto K Liyanage M Zhang MC Aban A Leen B Szardenings AK Rosenblum JS Kozarich JW Kohno Y Shreder KR 《Bioorganic & medicinal chemistry letters》2011,21(19):5948-5951
The synthesis, GSK-3β inhibitory activity, and anti-microbial activity of bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3-carboxylic acid scaffold were studied. Kinase selectivity profiling indicated that members of this class were potent and highly selective GSK-3 inhibitors. 相似文献
14.
《Phytochemistry》1986,25(11):2651-2652
Exogenously applied 1-amino-4-sulphonate-β-naphthol increased the oil content and altered the fatty acid composition of the semispreading variety C-501 of peanut. The content of oleic acid decreased while that oflinoleic acid increased in the kernels of treated plants. 相似文献
15.
The optimum geometries and binding energies of the complexes formed by AMPA and Kainic acid, as well as their anions with
tyrosine, proline and some tripeptides are investigated with quantum chemical calculations (HF/6-31G**). It was found that
receptors featuring the Tyr-Ala-Pro sequence exhibit stronger binding energies to the substrates than the Tyr-Ser-Pro and
Tyr-Ser-Ser. As expected, the anions are more bound than the neutral species. This work can lead to investigations on the
effect of AMPA receptors mutations on the brain functions, possibly related to criminal tendencies. 相似文献
16.
Methods for quantitative analysis of the carboxylated amino acids, aminomalonic acid, β-carboxyaspartic acid, and γ-carboxyglutamic acid, are presented. These substances are acid labile and thus can be measured only after alkaline hydrolysis of proteins and peptides. Half-times for decarboxylation in 1 m HCl at 100°C are: aminomalonic acid (1.2 min); β-carboxyaspartic acid (1.7 min); and γ-carboxyglutamic acid (8.6 min). This property is useful for unequivocal identification in complex hydrolysates. 相似文献
17.
《Bioorganic & medicinal chemistry》2019,27(20):114923
Diosgenyl 2-amino-2-deoxy-β-d-glucopyranoside is a semisynthetic saponin with antimicrobial and antitumor activities. To search for more effective analogues, N-aminoacyl and N-hydroxyacyl derivatives of this saponin were synthesized conventionally and with microwave assistance, and tested against the human pathogenic fungi and Gram-positive and Gram-negative bacteria. None of the tested compounds exhibit activity against Gram-negative bacteria. Almost all of the synthesized N-aminoacyl saponins exhibit antifungal activity and act effectively against Gram-positive bacteria, some better than the parent compound. The best acting saponins are the same size and possess sarcosine or l- or d-alanine attached to the parent glucosaminoside. Shorter and longer aminoacyl residues are less advantageous. d-Alanine derivative is the most effective against Gram positive bacteria. Structure-activity relationship (SAR) analysis indicates that the free α-amino group in aminoacyl residue is necessary for antimicrobial activities of the tested saponins. (N-Acetyl)aminoacyl and N-hydroxyacyl analogs are inactive. Measurements of the hemolytic activities demonstrate that the best acting saponins are not toxic towards human red blood cells. 相似文献
18.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1996,675(1):162-167
The main active cannabis (Marijuana and hashish) derivative Δ9-tetrahydrocannabinol is, in vivo, transformed and excreted mainly as 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) and its glucuronide. The method presented here allows the confirmation of the presence of THC-COOH by means of a basic hydrolysis, solid-phase extraction clean-up on reversed-phase (RP) disposable cartridges followed by analysis on a C8 RP column and UV detection; the mobile phase used was a 55% acetonitrile solution in acid phosphate buffer. Over 600 samples both from drug addicts in therapeutic communities and subjects who were not on any drugs therapy were analysed. This method was precise with a linearity range from 10 to more than 500 ng/ml [the lower limit proposed by the National Institute on Drug Abuse (NIDA) for cannabinoid confirmation method is 15 ng/ml]. The sample preparation is simple and fast, allowing the analysis of large numbers of samples. Perfect correlation was observed between data from the HPLC method and a fluorescence polarization immunoassay screening method. The THC-COOH metabolite was found to constitute 30% of all the cannabinoids excreted in urine of abusers. 相似文献
19.
Tyler S. Beyett Xinmin Gan Shannon M. Reilly Andrew V. Gomez Louise Chang John J.G. Tesmer Alan R. Saltiel Hollis D. Showalter 《Bioorganic & medicinal chemistry》2018,26(20):5443-5461
The non-canonical IκB kinases TANK-binding kinase 1 (TBK1) and inhibitor of nuclear factor kappa-B kinase ε (IKKε) play a key role in insulin-independent pathways that promote energy storage and block adaptive energy expenditure during obesity. Utilizing docking calculations and the x-ray structure of TBK1 bound to amlexanox, an inhibitor of these kinases with modest potency, a series of analogues was synthesized to develop a structure activity relationship (SAR) around the A- and C-rings of the core scaffold. A strategy was developed wherein R7 and R8 A-ring substituents were incorporated late in the synthetic sequence by utilizing palladium-catalyzed cross-coupling reactions on appropriate bromo precursors. Analogues display IC50 values as low as 210?nM and reveal A-ring substituents that enhance selectivity toward either kinase. In cell assays, selected analogues display enhanced phosphorylation of p38 or TBK1 and elicited IL-6 secretion in 3T3-L1 adipocytes better than amlexanox. An analogue bearing a R7 cyclohexyl modification demonstrated robust IL-6 production in 3T3-L1 cells as well as a phosphorylation marker of efficacy and was tested in obese mice where it promoted serum IL-6 response, weight loss, and insulin sensitizing effects comparable to amlexanox. These studies provide impetus to expand the SAR around the amlexanox core toward uncovering analogues with development potential. 相似文献
20.
《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2017,1862(5):561-571
Human 5-lipoxygenase (5-LO-WT) initiates the leukotriene (LT) biosynthesis. LTs play an important role in diseases like asthma, atherosclerosis and in many types of cancer. In this study, we investigated the 5-LO isoforms 5-LO∆13, 5-LO∆4 and 5-LOp12, lacking the exons 13, 4 or a part of exon 12, respectively. We were able to detect the mRNA of the isoforms 5-LO∆13 and 5-LOp12 in B and T cell lines as well as in primary B and T cells and monocytes. Furthermore, we found that expression of 5-LO and particularly of the 5-LO∆13 and 5-LOp12 isoforms is increased in monocytes from patients with rheumatoid arthritis and sepsis. Confocal microscopy of HEK293T cells stably transfected with tagged 5-LO-WT and/or the isoforms revealed that 5-LO-WT is localized in the nucleus whereas all isoforms are located in the cytosol. Additionally, all isoforms are catalytically inactive and do not seem to influence the specific activity of 5-LO-WT. S271A mutation in 5-LO-WT and treatment of the cells with sorbitol or KN-93/SB203580 changes the localization of the WT enzyme to the cytosol. Despite colocalization with the S271A mutant, the isoforms did not affect LT biosynthesis. Analysis of the phosphorylation pattern of 5-LO-WT and all the isoforms revealed that 5-LOp12 and 5-LO∆13 are highly phosphorylated at Ser271 and 5-LOp12 at Ser523. Furthermore, coexpression of the isoforms inhibited or stimulated 5-LO-WT expression in transiently and stably transfected HEK293T cells suggesting that the isoforms have other functions than canonical LT biosynthesis. 相似文献