变温培养对泰乐菌素发酵的影响

在泰乐菌素发酵过程中的不同阶段采用不同的培养温度,通过实验考察其对泰乐菌素发酵的影响。实验结果表明,变温培养的发酵水平要高于其它恒温培养的发酵水平。     

泰乐菌素及其衍生物研究进展

泰乐菌素是目前国际上广泛使用的兽用抗生素,国外对泰乐菌素的研究一直没有停止过。目前国内外通过生物转化和化学合成的手段,生产出一系列泰乐菌素的衍生物。这些衍生物在药效上大大高于泰乐菌素,在药物残留方面比泰乐菌素表现出很大的优势,有逐渐取代泰乐菌素的趋势。本文综述了目前国际上各种泰乐菌素的衍生物的结构性质及合成方法,并重点介绍了运用生物转化法合成乙酰异戊酰泰乐菌素的研究进展,对了解和研究泰乐菌素衍生物,制备新一代的高效低毒抗生素具有指导意义。     

双拷贝tylD、tylF和tylJ弗氏链霉菌工程菌株构建及其发酵性能研究

以弗氏链霉菌工业生产菌株基因组DNA为模板，扩增泰乐星生物合成及组分转化关键基因tylD、tylF和tylJ，构建双拷贝tylD、tylF、tylJ弗氏链霉菌工程菌株。通过摇瓶发酵验证了工程菌株泰乐菌素发酵效价，并对筛选的一株工程菌利用荧光定量PCR检测其tylD、tylF和tylJ基因表达情况。研究结果表明，双拷贝tylD、tylF、tylJ弗氏链霉菌工程菌株泰乐菌素摇瓶发酵效价较出发菌株最高提高了28.1%，该菌株tylD、tylF、tylJ表达水平高于出发菌株，并且在进入稳定期后期表达量达到最大值。构建双拷贝tylD、tylF、tylJ弗氏链霉菌工程菌株可解除泰乐菌素合成限速环节，大幅度的提高泰乐菌素产量。     

泰乐星在碳糊电极上的伏安行为研究及应用

目的 研究表面活性剂增敏作用下泰乐星(TLS)在碳糊电极(CPE)上的电化学行为,建立一种测定TLS的电化学分析方法 .方法 用循环伏安法(cyclic voltammetry,CV)和线性扫描伏安法(linear sweep voltammetry,LSV)探讨了TLS在CPE上的电化学行为及其影响因素.结果 阴离子表面活性剂十二烷基苯磺酸钠(SDBS)存在下TLS在CPE上有一显著的不可逆氧化峰,峰电位(Ep)为0.735V.结论 TLS氧化峰电流与其浓度在1.2×10-5～1.0 × 10-3mol/L范围内呈良好的线性关系,r=0.9974,检出限1.7×10-7mol/L,以此建立TLS含量的电化学分析方法 .测定结果 RSD1.6～2.4%,加样回收率98.6%～101.1%.该方法 简便快捷,测定结果 令人满意.     

16-membered macrolide antibiotics: a review

The 16-membered macrolide antibiotics (e.g. tylosin A and josamycin) are mainly used in veterinary medicine, and are much less studied than their 14- and 15-membered erythromycin-based cousins. Although these antibiotics have similar antibacterial profiles, with activity primarily against Gram-positive and a limited range of Gram-negative organisms, the 16–membered macrolides show some advantages. These include better gastrointestinal tolerance, lack of drug-drug interactions, and activity against certain resistant bacterial strains by extension of the peptide tunnel reach allowing additional interactions. In addition to antibacterial activity, the most famous representative of the class, tylosin A, as well as some derivatives of desmycosin (tylosin B), have shown antimalarial activity. Such activity has also been observed in the 14-membered macrolide antibiotics, azithromycin, solithromycin and clindamycin. This antimalarial activity provides the opportunity to investigate these drugs as cheap and effective antimalarials. This is an overview of the latest research on biosynthesis, structure, chemical properties and mode of action of 16-membered macrolides, with special emphasis on their most explored members: tylosin A and josamycin.     

透明颤菌血红蛋白基因在弗氏链霉菌中的表达及其对菌体生长和泰乐星合成的影响

质粒 p IJ4 0 2 6和 p RK4 0 4 - vhb分别含有红霉素抗性基因启动子 (Perm E)和透明颤菌血红蛋白基因 (vhb) ,先用 PCR分别扩增二者 ,再用 SOE- PCR(Splicing by overlap extension PCR)将不含自身启动子的vhb基因置于 Perm E之下 ;将 SOE- PCR产物克隆到链霉菌整合性载体 p SET15 2上 ,构建成 vhb基因表达载体 p WQ2 0 0 4。通过大肠埃希氏菌 -链霉菌属间接合转移的方式将 p WQ2 0 0 4导入弗氏链霉菌 (Streptomycesfradiae)中 ,利用 p WQ2 0 0 4上 Φ C31整合性位点使 vhb基因整合到弗氏链霉菌染色体上。PCR验证表明 ,vhb基因已整合到染色体上 ,CO结合差光谱分析则表明 vhb基因在弗氏链霉菌中成功表达。摇瓶与上罐发酵显示 vhb基因的表达可明显促进菌体生长与泰乐星的生物合成     

大孔吸附树脂提取泰乐星的研究

用几种典型的大孔吸附树脂对发酵过渡液中泰乐星吸附,筛选出Ｈ－３型树脂为吸附剂。静态实验表明,Ｈ－３型大孔吸附树脂对泰乐星吸附量达１５５。．９ｍｇ／ｇ干树脂,最佳吸附ＰＨ在７．５～８．０,吸附剂投入放量７％～８％（ｗ／Ｖ）,吸附时间６为最适宜吸附条件。其吸附等温线服从Ｆｒｅｕｎｄｌｉｃｈ吸曙式。以甲醇－柠檬酸缓冲液体系做洗脱剂,解吸率达８４．６％。选出以Ｄ２９０大孔碱性树脂为脱色剂。动态实验确定吸附     

纳滤膜技术在泰乐星提炼过程中的应用

泰乐星提炼过程中原工艺脱色液用薄膜真空浓缩,本试验改进为耐溶纳滤膜浓缩,料液不需要加热即可浓缩,防止了料液的高温分解破坏, 缩收率明显提高;在浓缩的同时,部分小分子杂质可以随水分子一起通过纳滤膜而除掉,成品质量明显提高,解决了用原工艺成品酪胺、溶解度不合格的质量问题;     

Aerobic degradation of tylosin in cattle,chicken, and swine excreta

Tylosin, a fermentation-derived macrolide antibiotic, was tested to determine its aerobic degradation rate in cattle, chicken, and swine excreta. For chicken, excreta from a hen administered 14C-tylosin as part of a metabolism study were used. For cattle and swine, 14C-tylosin was added to control excreta. The formation of 14C volatile breakdown products and 14CO2 was not observed throughout the study. Material balance for the carbon-14 label ranged between 94% and 104%. Initial, day-0, concentrations of tylosin-A averaged 119.52+/-4.39, 35.01+/-1.34, and 62.82+/-2.11 microg/g (dry weight basis) for cattle, chicken, and swine excreta samples, respectively. After 30 days, samples averaged 4.16+/-0.69 and 4.11+/-0.69 microg/g tylosin-A in cattle and swine excreta, respectively. No residues of tylosin-A or its factors were apparent in the chicken excreta samples after 30 days of incubation. In each case, tylosin declined to less than 6.5% of the initial level after 30 days. Calculated first-order half-lives under the test conditions were 6.2 days, <7.6 days, and 7.6 days for cattle, chicken, and swine excreta, respectively. The results indicate that tylosin residues degrade rapidly in animal excreta. Therefore, tylosin residues should not persist in the environment.