Global biogeographic sampling of bacterial secondary metabolism.
Global biogeographic sampling of bacterial secondary metabolism.
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DOI：
10.7554/elife.05048
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发表时间：
2015-01-19
期刊：
影响因子：
7.7
通讯作者：
Brady SF
中科院分区：
文献类型：
--
作者：
Charlop-Powers Z;Owen JG;Reddy BV;Ternei MA;Guimarães DO;de Frias UA;Pupo MT;Seepe P;Feng Z;Brady SF
最近的细菌（Meta）基因组测序的努力表明，存在一个巨大的未开发的天然产物编码的生物合成基因簇在环境中的水库。在这里，我们使用焦磷酸测序的PCR扩增子来自两个非核糖体肽腺苷酸化结构域和聚酮合酶结构域比较生物合成的多样性，在土壤微生物从周围的地球仪。除了最接近的和生物群系相似的样品外，我们发现所有样品的结构域群体存在很大差异，这表明大多数微生物组将编码大量不同的细菌次级代谢产物。我们的数据表明两个因素之间的相关性，地理距离和生物群系类型，以及土壤环境中发现的生物合成多样性。通过将读段分配给已知的基因簇，我们确定了生物医学相关的生物合成多样性的热点。这些观察不仅为自然界提供了新的见解，还为指导未来的天然产物发现工作提供了路线图。DOI：http://dx.doi.org/10.7554/eLife.05048.001许多最有用的药物--包括抗生素和抗癌药物--都是从生活在土壤中的细菌中提取的，这些细菌在其自然生命周期中产生这些化学物质。这些化学物质中有许多是通过在实验室中培养细菌发现的，但这种方法是有限的，因为它只提供了我们可以以这种方式培养的一小部分细菌物种产生的化学物质。此外，许多细菌在这些人工条件下生长时不会产生许多不同的化学物质，而不是在自然环境中生长。这表明，生活在环境中的细菌可能会提供额外的新化学物质来源，这些化学物质可能具有药用价值。在这里，Charlop-Powers等人通过采用高通量遗传方法来评估土壤细菌产生具有生物活性的化合物的潜力来解决这个问题。他们直接从五大洲收集的土壤样本中提取DNA，部分是通过一个名为“泥土中的毒品”（drugsfromdirt.org）的公民科学项目的努力。这些样本来自许多不同的环境，包括热带雨林，沙漠和沿海沉积物。从土壤样本中提取DNA后，Charlop-Powers等人专注于对编码NRPS和PKS酶的基因进行测序。这些酶参与生产一系列不同的化合物，包括许多临床上有用的抗生素。通过比较在不同土壤中发现的基因序列，可以估计基因在每个样本中的普遍程度，并比较在不同土壤类型中发现的基因集合。这种比较表明，编码NRPS和PKS的基因的DNA序列在土壤样品中差异很大，除了来自彼此接近的相似环境的样品。这些发现表明，生活在不同地点的土壤细菌种群可能会产生相关的，但不同的，大部分未开发的天然化合物，这些化合物可能有潜力用于药物治疗或其他行业。DOI：http://dx.doi.org/10.7554/eLife.05048.002
Recent bacterial (meta)genome sequencing efforts suggest the existence of an enormous untapped reservoir of natural-product-encoding biosynthetic gene clusters in the environment. Here we use the pyro-sequencing of PCR amplicons derived from both nonribosomal peptide adenylation domains and polyketide ketosynthase domains to compare biosynthetic diversity in soil microbiomes from around the globe. We see large differences in domain populations from all except the most proximal and biome-similar samples, suggesting that most microbiomes will encode largely distinct collections of bacterial secondary metabolites. Our data indicate a correlation between two factors, geographic distance and biome-type, and the biosynthetic diversity found in soil environments. By assigning reads to known gene clusters we identify hotspots of biomedically relevant biosynthetic diversity. These observations not only provide new insights into the natural world, they also provide a road map for guiding future natural products discovery efforts. DOI: http://dx.doi.org/10.7554/eLife.05048.001 Many of the most useful medicinal drugs—including antibiotics and cancer drugs—are derived from bacteria living in the soil that produce these chemicals as part of their natural life cycle. Many of these chemicals have been found by culturing bacteria in the laboratory, but this approach is limited because it only provides access to the chemicals produced by the small fraction of bacteria species that we can culture in this way. Also, many bacteria do not produce as many different chemicals when they are grown under these artificial conditions, instead of their natural environment. This suggests that bacteria living in the environment are likely to provide an additional source of new chemicals that could have medicinal benefits. Here, Charlop-Powers et al. tackle this issue by employing a high-throughput genetic method for assessing the potential of soil-dwelling bacteria to make compounds with biological activity. They extracted DNA directly from soil samples collected from five continents, in part through the efforts of a citizen-science project called ‘Drugs from Dirt’ (drugsfromdirt.org). These samples came from many different environments, including rainforests, deserts, and coastal sediments. After extracting the DNA from the soil samples, Charlop-Powers et al. focused on sequencing the genes that encode enzymes called NRPS and PKS. These enzymes are involved in the production of a range of diverse compounds, including many clinically useful antibiotics. By comparing the sequences of the genes found in the different soils, it was possible to estimate how common the genes were in each sample, and also to compare the collections of genes found in different soil types. This comparison revealed that the DNA sequences of the genes encoding NRPS and PKS vary widely among the soil samples, except for samples that came from similar environments in close proximity to each other. These findings show that populations of soil-dwelling bacteria living in different locations are likely to produce related, but different and largely unexplored, natural compounds that could have the potential to be used in drug therapies or in other industries. DOI: http://dx.doi.org/10.7554/eLife.05048.002