Microorganisms--degraders of polychlorinated biphenyls

Four strains belonging to the genus Bacillus, capable of degrading polychlorinated biphenyls (PCB), were isolated by screening the collection strains of soil bacteria, degrading a organochlorine pesticide, hexachlorocyclohexane (HCCH). A method for production of tritium-labeled PCB was developed. Consumption and degradation of PCB by the soil bacterial strains selected were studied using tritium-labeled PCB and GLC. It was demonstrated that PCB are degradable both in culture media and under in model soil samples.     

Aerobic degradation of polychlorinated biphenyls

The microbial degradation of polychlorinated biphenyls (PCBs) has been extensively studied in recent years. The genetic organization of biphenyl catabolic genes has been elucidated in various groups of microorganisms, their structures have been analyzed with respect to their evolutionary relationships, and new information on mobile elements has become available. Key enzymes, specifically biphenyl 2,3-dioxygenases, have been intensively characterized, structure/sequence relationships have been determined and enzymes optimized for PCB transformation. However, due to the complex metabolic network responsible for PCB degradation, optimizing degradation by single bacterial species is necessarily limited. As PCBs are usually not mineralized by biphenyl-degrading organisms, and cometabolism can result in the formation of toxic metabolites, the degradation of chlorobenzoates has received special attention. A broad set of bacterial strategies to degrade chlorobenzoates has recently been elucidated, including new pathways for the degradation of chlorocatechols as central intermediates of various chloroaromatic catabolic pathways. To optimize PCB degradation in the environment beyond these metabolic limitations, enhancing degradation in the rhizosphere has been suggested, in addition to the application of surfactants to overcome bioavailability barriers. However, further research is necessary to understand the complex interactions between soil/sediment, pollutant, surfactant and microorganisms in different environments.     

Bacterial metabolism of polychlorinated biphenyls

Microbial metabolism is responsible for the removal of persistent organic pollutants including PCBs from the environment. Anaerobic dehalogenation of highly chlorinated congeners in aquatic sediments is an important process, and recent evidence has indicated that Dehalococcoides and related organisms are predominantly responsible for this process. Such anaerobic dehalogenation generates lower chlorinated congeners which are easily degraded aerobically by enzymes of the biphenyl upper pathway (bph). Initial biphenyl 2,3-dioxygenases are generally considered the key enzymes of this pathway which determine substrate range and extent of PCB degradation. These enzymes have been subject to different protein evolution strategies, and subsequent enzymes have been considered as crucial for metabolism. Significant advances have been made regarding the mechanistic understanding of these enzymes, which has also included elucidation of the function of BphK glutathione transferase. So far, the genomes of two important PCB-metabolizing organisms, namely Burkholderia xenovorans strain LB400 and Rhodococcus sp. strain RHA1, have been sequenced, with the rational to better understand their overall physiology and evolution. Genomic and proteomic analysis also allowed a better evaluation of PCB toxicity. Like all bph gene clusters which have been characterized in detail, particularly in strains LB400 and RHA1, these genes were localized on mobile genetic elements endowing single strains and microbial communities with a high flexibility and adaptability. However, studies show that our knowledge on enzymes and genes involved in PCB metabolism is still rather fragmentary and that the diversity of bacterial strategies is highly underestimated. Overall, metabolism of biphenyl and PCBs should not be regarded as a simple linear pathway, but as a complex interplay between different catabolic gene modules.     

A chromosomal study on blood lymphocytes of patients poisoned by polychlorinated biphenyls

Chromosome studies were carried out on peripheral blood lymphocytes from 36 PCB-poisoned patients and on ten PCB-unexposed healthy controls. Nineteen out of 36 patients (52.7%) had either chromosome or chromatid aberrations, while none of the controls had. The highest percentage of cells with chromosome or chromatid aberrations in a single individual was 34.0. The blood PCB level ranged from 6.4 to 101.8 ppb, with a mean of 34.1 ppb. No correlation was observed between the level of blood PCB and the presence or absence of chromosome or chromatid aberrations.     

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.     

Peptide-membrane interactions and a new principle in quantitative structure-activity relationships.

Ideas about “active conformations” of peptides as the basis of their biological action are reviewed and put into perspective with recent work on the possible role of the lipid phase of the target cell membrane in mediating receptor subtype selectivity.     

Comparative quantitative structure-activity study of radical scavengers

Classic and three-dimensional (3-D) QSAR analyses of 13 radical scavengers (1-13) were performed to derive two classic, two Apex-3-D and one comparative field analysis (CoMFA) models. Two classical models with predictive cross-validated r2 (Q2) over 0.96 indicated that the activity was attributed to the electronic COH and ELUMO, steric molar refractivity (MR) and lipophilic log P. Three-dimensional quantitative structure-activity relationship (3-D-QSAR) studies were performed by 3-D pharmacophore generation (Apex-3-D) and CoMFA techniques. For Apex-3-D studies, two best models with high Q2 (0.94 and 0.97) were yielded. Structural properties contributing to the activity were not only lipophilic but also the optimum steric property and geometry of side-chain composition. For CoMFA studies, the sp3 C(+1) probe provided the best Q2 of 0.79 with steric and electrostatic contributions of 42.3 and 57.7%, respectively. The activity of four new compounds (14-17) not included in the derivation were predicted with these models. Although the derived models were from limited data, the statistic relation was predictive. The linear correlations between the experimental IC50 values and the predicted values from classical and Apex-3-D models were found to be high and significant. The predicted activity of 17 from CoMFA was much lower than the experimental value; this deviation occurred according to the missing of hydrophobic field in standard CoMFA study. In vitro and ex vivo antilipid peroxidation in mouse brain and ESR studies of 14-17 were investigated for the radical-scavenging ability. The difference between the in vitro results, antilipid peroxidation and electron spin resonance (ESR) and ex vivo results in coumarin series was found. Thus, other properties for good bioavailability besides log P should also be taken into consideration.     

Cytotoxicity of salicylaldehyde benzoylhydrazone analogs and their transition metal complexes: quantitative structure-activity relationships

A series of salicylaldehyde benzoylhydrazone derivatives, their copper(II) complexes and a range of transition metal complexes of the unsubstituted ligand has been synthesized and evaluated for cytotoxicity against a human adenocarcinoma cell line. A QSAR analysis revealed ligand cytotoxicity is strongly correlated with electronic and transport factors and can be modeled by treating each 'half' of the molecule as an isolated unit. Activity increases when substituents in the benzoyl ring were electron withdrawing whereas, for the salicylaldehyde ring, electron donation was required. The cytotoxicity of the Cu(II) complexes was greater than, and paralleled the ligands. Activity for the transition metal complexes of the unsubstituted ligand mirrored charge density on the metal.     

微生物降解多氯联苯的研究进展

多氯联苯是一种持续性有机污染物,在自然环境中很难降解。在目前研究的降解方法中,微生物降解最具潜力。本文对多氯联苯微生物降解的研究进展进行了综述,包括厌氧还原脱氯,好氧氧化以及生物表面活性剂的作用,介绍了几种降解方法耦合应用的现状和前景,指出了应用中存在的问题和今后的发展方向。     

Epibatidine structure-activity relationships

Epibatidine is a potent but nonselective nAChR agonist. Its biological effects appear to be mediated largely by alpha4beta2 nAChRs. Surprisingly, only a limited number of epibatidine analogues have been synthesized and evaluated in in vitro assays. Even fewer analogues have received in vivo pharmacological evaluation. In this paper, SAR studies directed toward epibatidine analogues will be reviewed.     

Strategies for bioremediation of polychlorinated biphenyls

Polychlorinated biphenyls (PCBs) are serious environmental pollutants that threaten both the natural ecosystem and human health. For remediation of environments contaminated with PCBs, several approaches that exploit the potential of microbes to degrade PCBs have been developed. These approaches include improvement of PCB solubilization and entry into the cell, pathway and enzyme engineering, and control of enzyme expression. In this mini-review, we briefly summarize these strategies and provide potentially useful knowledge for the further improvement of the bacterial breakdown of PCBs.     

Microbial reductive dehalogenation of polychlorinated biphenyls

Under anaerobic conditions, microbial reductive dechlorination of polychlorinated biphenyls (PCBs) occurs in soils and aquatic sediments. In contrast to dechlorination of supplemented single congeners for which frequently ortho dechlorination has been observed, reductive dechlorination mainly attacks meta and/or para chlorines of PCB mixtures in contaminated sediments, although in a few instances ortho dechlorination of PCBs has been observed. Different microorganisms appear to be responsible for different dechlorination activities and the occurrence of various dehalogenation routes. No axenic cultures of an anaerobic microorganism have been obtained so far. Most probable number determinations indicate that the addition of PCB congeners, as potential electron acceptors, stimulates the growth of PCB-dechlorinating microorganisms. A few PCB-dechlorinating enrichment cultures have been obtained and partially characterized. Temperature, pH, availability of naturally occurring or of supplemented carbon sources, and the presence or absence of H(2) or other electron donors and competing electron acceptors influence the dechlorination rate, extent and route of PCB dechlorination. We conclude from the sum of the experimental data that these factors influence apparently the composition of the active microbial community and thus the routes, the rates and the extent of the dehalogenation. The observed effects are due to the specificity of the dehalogenating bacteria which become active as well as changing interactions between the dehalogenating and non-dehalogenating bacteria. Important interactions include the induced changes in the formation and utilization of H(2) by non-dechlorinating and dechlorinating bacteria, competition for substrates and other electron donors and acceptors, and changes in the formation of acidic fermentation products by heterotrophic and autotrophic acidogenic bacteria leading to changes in the pH of the sediments.     

多氯联苯的生物修复

多氯联苯(Polychlorinated biphenyls,PCBs)是一种持久性有机污染物,对人类和自然环境具有很大的威胁,降解PCBs一直是研究的热点。在目前的研究方法中生物降解最具潜力,生物降解主要分为微生物降解、植物修复和微生物-植物共同修复3个方面。文章着重介绍了微生物降解PCBs菌株的分离,降解相关基因的克隆和改造;同时对植物修复,植物与微生物共同修复以及植物转基因修复进行了讨论。     

Hologram quantitative structure-activity relationships for a series of farnesoid X receptor activators

The farnesoid X receptor (FXR) is an attractive drug target for the development of novel therapeutic agents for the treatment of dyslipidemia and cholestasis. Hologram quantitative structure-activity relationship (HQSAR) studies were conducted on a series of potent FXR activators originated from natural product-like libraries. A training set containing 82 compounds served to establish the models. The best HQSAR model was generated using atoms, bonds, connections, chirality, and donor and acceptor as fragment distinction and fragment size default (4-7) with six components. The model was used to predict the potency of 20 test set compounds that were not included in the training set, and the predicted values were in good agreement with the experimental results. The final HQSAR model and the information obtained from HQSAR 2D contribution maps should be useful for the design of novel FXR ligands having improved potency.     

Conformational analysis of rhazinilam and three-dimensional quantitative structure-activity relationships of rhazinilam analogues

3D QSAR of rhazinilam (1), an alkaloid isolated from Rhazya stricta (Apocynaceae) with an activity involving disassembly of microtubules and its derivatives was investigated by using the comparative molecular field analysis (CoMFA). In an effort to get a better understanding of the correlation between conformation and antitubulin activity of 1, most probable minimum energy conformation in solution of 1 was analyzed on the basis of NMR data of 1 in solution. The results indicated a correlation between the antitubulin activity of these alkaloids and the steric and electrostatic factors, which modulate their biological activity, and accounted for the potent activities of 1 with suitable relationship for the overall conformation.