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Identifying Natural Product Biosynthetic Genes from a Soil Metagenome by Using T7 Phage Selection

机译:通过使用T7噬菌体选择从土壤基因组中鉴定天然产物生物合成基因

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Microbes from the natural environment have long been a major source of therapeutic reagents. During the golden age of antibiotic discovery, the natural products penicillin, vancomycin, and tetracycline were identified from bacterial culture and achieved historic success in mankind’s battle against infectious diseases. Currently, natural product molecules continue to contribute to the drug development pipeline. However, the poor yield of new chemical entities from bacterial culture has forced the pharmaceutical industry to scale down drug discovery programs based on natural products.One reason for the low success rate in the isolation of new bioactive compounds of bacterial origin is that less than 1% of microorganisms in nature are cultivable with current laboratory techniques.Consequently, only a minimal fraction of the natural product repertoire is accessible for activity-based screening with conventional cell culturing methods.
机译:长期以来,来自自然环境的微生物一直是治疗试剂的主要来源。在抗生素发现的黄金时代,从细菌培养物中鉴定出了天然产物青霉素,万古霉素和四环素,它们在人类与传染病的斗争中取得了历史性的成功。当前,天然产物分子继续为药物开发渠道做出贡献。然而,细菌培养产生的新化学实体收率不高,迫使制药行业缩减了基于天然产物的药物发现计划的规模。分离细菌来源的新生物活性化合物成功率低的原因之一是,不到1自然界中有%的微生物可以通过当前的实验室技术进行培养。因此,使用常规细胞培养方法进行基于活性的筛选时,只有极少部分的天然产物可以用于活性筛选。

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