天然的化合物曾经一度是FDA批准新药的主要来源，而且细菌是这些治疗性化合物最大的单一来源。许多细菌衍生的抗生素和抗癌制剂都是通过培养环境中的细菌所得到的，但是环境中大部分的细菌都不能在实验室中进行培养，这就建议我们应该加大对于这些环境中细菌的研究力度，并且发现其潜在未知的机制。
近日，刊登在国际杂志Applied and Environmental Microbiology上的一篇文章中，来自霍华休斯医学研究中心研究者Sean Brady和其同事从美国西南地区的土壤中提取出了土壤细菌的DNA，随后研究者用DNA来构建宏基因组DNA文库，用主要的三种小分子生物合成系统来筛选这些文库，这三种小分子生物合成系统包括一型模块化多酮类化合物；二型迭代多酮类化合物和非核糖体肽类。
研究者使用PCR的方法来扩增来自三种文库中筛选得到的基因片段，并且比较收集其相似性和区别，Brady表示，我们的研究工作揭示了，环境中细菌的基因组可以编码很多类似药物的小分子，当然其中有些小分子化合物是具有潜在的治疗价值的。我们的研究只是一项规模很小的研究，我们鼓励别的科学家也投入到这项研究中来，这样就可以提供更为宽广的序列分析，因为我们认为环境中的细菌具有很大的潜力，来产生潜在治疗价值的新药。（生物谷：T.Shen编译）
doi:10.1128/AEM.00102-12
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PMID:
Natural Product Biosynthetic Gene Diversity in Geographically Distinct Soil Microbiomes
Boojala Vijay B. Reddy, Dimitris Kallifidas, Jeffrey H. Kim, Zachary Charlop-Powers, Zhiyang Feng and Sean F. Brady
The number of bacterial species estimated to exist on Earth has increased dramatically in recent years. This newly recognized species diversity has raised the possibility that bacterial natural product biosynthetic diversity has also been significantly underestimated by previous culture-based studies. Here, we compare 454-pyrosequenced nonribosomal peptide adenylation domain, type I polyketide ketosynthase domain, and type II polyketide ketosynthase alpha gene fragments amplified from cosmid libraries constructed using DNA isolated from three different arid soils. While 16S rRNA gene sequence analysis indicates these cloned metagenomes contain DNA from similar distributions of major bacterial phyla, we found that they contain almost completely distinct collections of secondary metabolite biosynthetic gene sequences. When grouped at 85% identity, only 1.5% of the adenylation domain, 1.2% of the ketosynthase, and 9.3% of the ketosynthase alpha sequence clusters contained sequences from all three metagenomes. Although there is unlikely to be a simple correlation between biosynthetic gene sequence diversity and the diversity of metabolites encoded by the gene clusters in which these genes reside, our analysis further suggests that sequences in one soil metagenome are so distantly related to sequences in another metagenome that they are, in many cases, likely to arise from functionally distinct gene clusters. The marked differences observed among collections of biosynthetic genes found in even ecologically similar environments suggest that prokaryotic natural product biosynthesis diversity is, like bacterial species diversity, potentially much larger than appreciated from culture-based studies.
