Expression and isolation of antimicrobial small molecules from soil DNA libraries.
Expression and isolation of antimicrobial small molecules from soil DNA libraries.
复制标题
土壤 DNA 文库中抗菌小分子的表达和分离。
DOI：
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发表时间：
2001
影响因子：
1.2
通讯作者：
M. Osburne
中科院分区：
文献类型：
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作者：
I. Macneil;C. L. Tiong;C. Minor;P. August;T. Grossman;K. Loiacono;B. Lynch;T. Phillips;S. Narula;R. Sundaramoorthi;A. Tyler;T. Aldredge;H. Long;M. Gilman;D. Holt;M. Osburne
天然产物一直是临床相关小分子疗法的重要来源。然而，抗菌剂分子的新结构类别的发现率有所下降。最近，越来越多的证据表明，从土壤中种植的物种数量不到总人口的1%，这为这些未培养的物种提供了一个巨大的未开发的池塘，从中可以发现新的天然产品，这是一种令人兴奋的可能性。我们构建了一个含有直接从土壤生物中分离的基因组片段(5-120kb)的细菌人工染色体文库(S-DNA)，并在大肠杆菌中表达。通过对文库的筛选，鉴定了不同重组克隆表达的几种抗菌活性。一个克隆(mg1.1)已经被部分鉴定并发现表达几个与靛玉红相关的小分子，并且包括它。这些结果表明，参与天然产物合成的基因可以直接从S的脱氧核糖核酸中克隆并在异源宿主中表达，支持了这一技术有可能从丰富的环境微生物多样性中提供新的天然产物的想法，是潜在的重要的药物发现的新工具。
Natural products have been a critically important source of clinically relevant small molecule therapeutics. However, the discovery rate of novel structural classes of antimicrobial molecules has declined. Recently, increasing evidence has shown that the number of species cultivated from soil represents less than 1% of the total population, opening up the exciting possibility that these uncultured species may provide a large untapped pool from which novel natural products can be discovered. We have constructed and expressed in E. coli a BAC (bacterial artificial chromosome) library containing genomic fragments of DNA (5-120kb) isolated directly from soil organisms (S-DNA). Screening of the library resulted in the identification of several antimicrobial activities expressed by different recombinant clones. One clone (mg1.1) has been partially characterized and found to express several small molecules related to and including indirubin. These results show that genes involved in natural product synthesis can be cloned directly from S-DNA and expressed in a heterologous host, supporting the idea that this technology has the potential to provide novel natural products from the wealth of environmental microbial diversity and is a potentially important new tool for drug discovery.
影响因子：
4.4
作者：
Osoegawa, K;Woon, PY;de Jong, PJ
通讯作者：
de Jong, PJ