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提高抗生素有效组分产量的生物学方法 总被引:1,自引:0,他引:1
综述了提高抗生素有效组分产量的4类生物学方法。随机诱变筛选和定向推理选育;在发酵培养基中添加前体或诱导物;改变培养基组成或控制发酵条件;基因工程理性化筛选。 相似文献
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青霉素高产菌株的推理选育 总被引:3,自引:0,他引:3
抗生素产生菌的推理选育是建立在抗生素生物合成机制已知或较清楚的基础上按需要定向选育的一种方法。近几年研究较多,应用较广,成效亦较为显著。就青霉素而言,经过多年的研究,其代谢机理已较清楚。实践证明,推理选育在青霉素育种上的应用其效果远比传统的随机筛选优越得多,只需适量筛选,即可达到所期望的目的。1 材料与方法1.1 材料1.1.1 菌株 青霉素产生菌H-106#。1.1.2 培养基斜面分离培养基(%)蛋白胨:0.6,葡萄糖:1.5,NaCl:0.5,KCl:0.05,KH2PO4:0.03,MgS… 相似文献
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阿维拉霉素高产菌株的选育 总被引:3,自引:0,他引:3
目的诱变选育阿维拉霉素高产菌株。方法紫外线随机诱变结合阿维拉霉素、2-氧-D-葡萄糖和高浓度CaCl2抗性筛选的推理选育方案。结果通过选育获得了抗CaCl2的高产菌株Avl-104,其阿维拉霉素产量为800mg/L,产量较出发菌株提高了217.4%。稳定性研究发现Avl-104具有遗传不稳定的特性,菌种高产特性退化严重,但通过自然分纯的方法,得到菌株Avl-104-312,其阿维拉霉素产量达1 222 mg/L。结论紫外随机诱变结合高浓度CaCl2抗性推理选育辅以自然分纯可以提高阿维拉霉素的产素能力。利用阿维拉霉素高产菌株的遗传不稳定性,通过自然分纯,不但可以维持其原有的高产特性,也可以进一步提高高产菌株的产素能力。 相似文献
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替考拉宁产生菌TA2—2组分高含量菌种的推理选育 总被引:4,自引:1,他引:3
以缬氨酸氧肟酸为筛选剂,对替考拉宁产生菌替考游动放线菌(Actinoplanes teichomyceticus)进行了推理选育,获得了发酵总效价和TA2-2组分含量均较出发菌株高的缬氨酸氧肟酸抗性变株98-1-227。传代试验表明菌株0227的遗传特性较。对菌株980-10227和出发菌株97-4-74的形态、生代特性进行比较。 相似文献
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选育优良微生物菌株对微生物药物研发尤其是对微生物制药实现产业化具有至关重要的意义。抗生素抗性筛选基于微生物对抗生素产生抗性,因其实验操作简便、效果显著而在有用微生物菌株选育中得到广泛应用。在微生物药物领域抗生素抗性筛选技术主要用来筛选获取高产菌株,但近来发现微生物的抗生素抗性突变可赋予突变株新生次级产物的代谢生产能力,因此在拓展药源微生物资源领域具有潜在应用价值。本文主要综述抗生素抗性筛选在微生物菌株选育中的作用以及相关新近研究进展。 相似文献
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目的:建立原发性高血压合理用药类别筛选模型并检验其在实践中的应用。方法:抽取大连医科大学附属第二医院2017年3月至2018年12月心内科门诊和住院的原发性高血压患者的医嘱记录,共计4 597条,再从以上记录中筛选出满足纳入标准的549条记录。医嘱记录均为高血压治疗达标患者,且为单药治疗,患者信息完整。判别分析模型建立过程中,分组变量的选择是根据管理学80/20法则找出占比例80%以上的药物分类,自变量的选择是采用单变量分析的方法筛选。用549条记录中的384条(70%)建立模型,求解判别函数,剩余165条(30%)用于训练模型,以验证模型的预测效果。结果:分析得出,纳入病例中血管紧张素类、β受体阻滞剂类、钙拮抗类三类药品的应用合占所有用药类别的94%,将它们作为判别分析的分组变量,然后从10个自变量中采用单变量分析方法筛选出对用药分类筛选具有显著统计学意义的自变量,结果年龄、就诊时情况、既往用药和主要合并疾病被选为自变量(P<0.05),用于建模,模型拟合良好,可以进行原发性高血压合理用药类别筛选。通过验证,该模型的准确率在50%左右。结论:原发性高血压合理用药类别筛选模型可提高原发性高血压治疗中的合理用药水平。 相似文献
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Introduction: Dysregulation of energy homeostasis has been implicated in a number of human chronic diseases including diabetes, obesity, cancer, and inflammation. Given the functional attributes as a central regulator of energy homeostasis, AMP-activated protein kinase (AMPK) is emerging as a therapeutic target for these diseases, and lines of evidence have highlighted the need for rational and robust screening systems for identifying specific AMPK modulators with a therapeutic potential for preventing and/or curing these diseases.Areas covered: Here, the authors review the recent advances in the understanding of three-dimensional structures of AMPK in relationship with the regulatory mechanisms, potentials of AMPK as a therapeutic target in human chronic diseases, and prospects of computer-based drug design for AMPK.Expert opinion: Accumulating information of AMPK structure has provided us with deep insight into the molecular basis underlying the regulatory mechanisms, and further discloses several structural domains, which can be served for a target site for computer-based drug design. Molecular docking and simulations provides useful information about the binding sites between potent drugs and AMPK as well as a rational screening format to discover isoform-specific AMPK modulators. For these reasons, the authors suggest that computer-aided virtual screening methods hold promise as a rational approach for discovering more specific AMPK modulators. 相似文献
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Shoemaker RH Scudiero DA Melillo G Currens MJ Monks AP Rabow AA Covell DG Sausville EA 《Current topics in medicinal chemistry》2002,2(3):229-246
Increasing insight into the genetics and molecular biology of cancer has resulted in the identification of an increasing number of potential molecular targets for anti-cancer drug discovery and development. These targets can be approached through exploitation of emerging structural biology, "rational" drug design, screening of chemical libraries, or a combination of these methods. In this article we discuss the application of high-throughput screening to anti-cancer drug discovery, with special reference to approaches used at the U.S. National Cancer Institute. 相似文献
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目的:制定某院老年2型糖尿病患者合理用药的评价标准,为保障临床合理用药提供依据。方法:将美国老年医学会发布的2019版老年人潜在不适当用药标准(Beers)、中国老年人潜在不适当用药判断标准(2017年版)、老年人不适当处方筛查工具(STOPP)、老年人处方遗漏筛查工具(START)、中国2型糖尿病防治指南(2017年版)和降糖药物最新版说明书中老年用药项下的内容汇总,提取相关条目并筛重整理,得到老年2型糖尿病患者合理用药的初始标准并形成调研问卷,再通过德尔菲法开展两轮专家问卷调研,得到最终标准。结果:参与本研究的专家共13人,两轮问卷的回收率均为100%、权威系数分别为0.75和0.78,以指标均数>3.5且变异系数<0.25为入选标准,本研究最终纳入21个警示指标。结论:本标准的制定结合了理论与临床经验,更具应用价值,可为该院老年2型糖尿病患者的合理用药提供依据,也可为药学人员处方审核提供参考。 相似文献
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Novel drugs presently introduced in the market are largely not discovered by rational design or by random screening but, rather, are products of evolution of existing leads (analogue research). It is suggested that this will change in the near future. Progress in a number of scientific disciplines will make it likely that drug design, but also systematic screening, will contribute more and more to novel drug discovery. 相似文献
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Zhao H Xin Z Liu G Schaefer VG Falls HD Kaszubska W Collins CA Sham HL 《Journal of medicinal chemistry》2004,47(27):6655-6657
A case study of rational design of an efficient, specific, and proprietary molecular scaffold based on the structure-activity relationship (SAR) information on a screening hit is described. Potent, selective, and orally bioavailable tetralin carboxamide growth hormone secretagogue receptor (GHS-R) antagonists were discovered. Union of rational design and high throughput synthesis provided a quick access to high quality chemical leads. 相似文献