变异链球菌UA140产生的细菌素(mutacin和mutacin)

细菌素是由细菌核糖体合成的肽类抗生素。根据翻译后的修饰作用情况 ,将革兰氏阳性菌细菌素分为2类 : 类 ,修饰的细菌素 ,即 lanbiotic类 ; 类 ,未修饰的细菌素 ,即非 lanbiotic类。lanbiotic类为含羊毛硫氨酸的小肽抗生素 ,通过翻译后的修饰作用形成脱水氨基酸残基和硫脂桥。非 lanbiotic类细菌素可以分为 2类 :单肽细菌素和双肽细菌素。非 lanbiotic类细菌素的生物合成涉及一个前肽的合成 ,该前肽由一个在加工位点具有 2个甘氨酸的先导肽和成熟肽部分组成 ,在成熟过程中 ,通过 1个专门的蛋白酶在 2个甘氨酸后的区域切下先导肽 ,释放出成熟…     

硫醚抗生素生物合成的遗传学

1988年Sehnell等首次创造了硫醚抗生素(lantibiotics)这个词，用于描述数目激增的细菌来源的并特征性地带有羊毛硫氨酸等硫醚氨基酸的肽类抗生紊。硫醚氨基酸最先是在一种广泛应用于食品防腐的抗微生物小肽乳链菌肽(nisin)中发现的。乳链菌肽舍有     

一株产广谱细菌素乳酸菌S3菌株的菌种鉴定

乳酸菌广泛分布于自然界,细菌素是由某些细菌通过核糖体合成机制产生的一类具有抑菌生物活性的蛋白质,抑菌范围不仅仅局限于同源的细菌,产生菌对其细菌素有自身免疫性。当革兰阳性菌产生的羊毛硫抗生素乳链菌肽(nisin)被科研人员发现并被认为可作为天然防腐剂以替代化学防腐剂应用在     

湖泊放线菌SIIA-A16124的分类鉴定及基因组挖掘

目的 对湖泊放线菌SIIA-A16124进行分类鉴定和基因组挖掘。方法 采用多相分类法对菌株的形态学、生理生化、细胞壁化学组分、16S rRNA基因序列进行测定和分类鉴定,采用基因组挖掘分析生物合成基因簇,经发酵培养、抗菌活性检测及活性产物质谱分析,推测其活性产物的化合物结构类别。结果 菌株SIIA-A16124的16S rRNA基因与菌株Actinokineospora inagensis NRRL B-24050T同源性最高为99%;菌株SIIA-A16124在ISP3培养基上中等产孢和水解淀粉的特性与模式菌株存在明显差异;鉴定菌株SIIA-A16124为动孢菌Actinokineospora sp.,具有羊毛硫肽生物合成基因簇,其活性次级代谢产物属于羊毛硫肽类抗生素。结论 首次发现动孢菌属放线菌具有生物合成羊毛硫肽类抗生素的能力。     

羊毛硫抗生素的研究进展及其应用

抗生素耐药性病原体在全球范围内的出现使得目前大多数使用的抗生素失去了原有的治疗效果,这就迫使人们急切需要开发出新的抗菌药物.羊毛硫抗生素(Lantibiotics)是革兰阳性菌通过核糖体合成机制产生的一类抗菌肽,可抑制微生物尤其是革兰阳性菌株的生长,有望可以代替传统抗生素控制耐药性病原菌.本文根据目前羊毛硫抗生素的研究,对羊毛硫抗生素的分类,作用机制和耐药性以及羊毛硫抗生素生物工程和应用进展进行了综述,并简单介绍了与羊毛硫抗生素相关的细菌素数据库.     

脂多糖缺失所致多黏菌素耐药的鲍曼不动杆菌研究进展

多黏菌素E(黏菌素)和多黏菌素B已成为治疗广泛耐药的革兰阴性菌感染的“最后一条防线”。但是，近年来有关鲍曼不动杆菌对多黏菌素的耐药性时有报道，尤其是有关脂多糖(LPS)缺失或修饰导致多黏菌素耐药的鲍曼不动杆菌各方面性质的改变，如细菌适应性下降，外膜合成相关基因表达增加，对其他抗生素敏感性提高，机械强度降低，细菌毒力下降，固有免疫因子水平变化等。本文将对近年来有关LPS缺失引起的鲍曼不动杆菌各方面性质变化的研究进行简要的综述。     

刺糖多胞菌合成多杀菌素的基因研究

多杀菌素是由刺糖多孢菌产生的一种新型大环内酯类混合次级代谢产物,为新型、高效、安全的生物杀虫剂。该类化合物由一个12元大环内酯以及一个中性糖和一个胺糖构成。多杀菌素生物合成基因大部分聚集在刺糖多孢菌基因组上约80kb大小的区域中。该区域DNA已被完全测序,并通过破坏目的基因的方法,对这一区域DNA的特性和功能进行了深入研究。多杀菌素生物合成基因簇包括5个编码Ⅰ型聚酮合成酶的基因和14个与大环内酯结构修饰有关的基因,另外还有4个编码鼠李糖的基因未包含在上述基因簇中。     

匹马菌素的生物合成研究进展

匹马菌素是纳塔链霉菌产生的一种安全、高效的多烯大环类真菌抑制剂,广泛应用于医药领域与食品工业.作为26元环的糖基化多烯大环聚酮,其生物合成基因簇长度约110kb,包含19个基因,编码5个聚酮合酶、10个修饰和转运蛋白及4个调控因子.本文分析了匹马菌素生物合成的基因基础、多烯聚酮合成过程、氧化和糖基化修饰与调控机理等最新研究进展,展望了利用组合生物合成进行基因簇改造的方案与应用前景.     

组合生物合成技术在药物研发中的应用

介绍组合生物合成技术在药物发现中的应用情况及研究进展。近年来迅速发展的组合生物合成技术为微生物活性代谢产物的结构修饰提供了新的方法,利用该技术,通过基因水平的改造,可获得结构新颖的化合物,为药物筛选拓宽了来源。     

阿维菌素产生菌的生物技术改造研究进展

目的综述近年来运用基因工程技术对阿维菌素产生菌改良的研究进展。方法在查阅国内外文献近100篇的基础上,介绍了阿维菌素的生物合成途径,产生多组分的3个关键酶及阿维菌素产生菌改良的研究进展,包括选择性生产有效组分,产生新抗生素、杂合抗生素,改进生产工艺以及提高菌种产抗生素量。结果目前国内外均已经构建了只产生B组分及寡霉素基因缺失或失活的工程菌。分别运用突变结合理性化筛选和特定基因重组提高活性高的组分的产量,并且通过基因改造产生多种阿维菌素的衍生物;将透明颤菌的血红蛋白基因引入阿维菌素产生菌,改进氧的供应,阿维菌素的产量不断提高。阿维菌素生物合成调控机制和组合生物学改造聚酮合成酶等方面仍需深入研究。结论利用生物技术改造阿维菌素产生菌在组分改造、结构修饰、产品收率、生产工艺改进等方面已取得显著进展。对阿维菌素和其他聚酮体药物产生菌的生物合成、基因改造起着重要作用,使生产简化,成本降低,药物应用更广泛。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.