天然的化合物曾經(jīng)一度是FDA批準(zhǔn)新藥的主要來源,，而且細(xì)菌是這些治療性化合物最大的單一來源,。許多細(xì)菌衍生的抗生素和抗癌制劑都是通過培養(yǎng)環(huán)境中的細(xì)菌所得到的，但是環(huán)境中大部分的細(xì)菌都不能在實(shí)驗(yàn)室中進(jìn)行培養(yǎng),，這就建議我們應(yīng)該加大對于這些環(huán)境中細(xì)菌的研究力度,，并且發(fā)現(xiàn)其潛在未知的機(jī)制,。
近日,，刊登在國際雜志Applied and Environmental Microbiology上的一篇文章中,，來自霍華休斯醫(yī)學(xué)研究中心研究者Sean Brady和其同事從美國西南地區(qū)的土壤中提取出了土壤細(xì)菌的DNA，隨后研究者用DNA來構(gòu)建宏基因組DNA文庫,，用主要的三種小分子生物合成系統(tǒng)來篩選這些文庫，這三種小分子生物合成系統(tǒng)包括一型模塊化多酮類化合物,；二型迭代多酮類化合物和非核糖體肽類,。
研究者使用PCR的方法來擴(kuò)增來自三種文庫中篩選得到的基因片段，并且比較收集其相似性和區(qū)別,，Brady表示,，我們的研究工作揭示了，環(huán)境中細(xì)菌的基因組可以編碼很多類似藥物的小分子,，當(dāng)然其中有些小分子化合物是具有潛在的治療價值的,。我們的研究只是一項(xiàng)規(guī)模很小的研究，我們鼓勵別的科學(xué)家也投入到這項(xiàng)研究中來,，這樣就可以提供更為寬廣的序列分析,，因?yàn)槲覀冋J(rèn)為環(huán)境中的細(xì)菌具有很大的潛力，來產(chǎn)生潛在治療價值的新藥,。（生物谷：T.Shen編譯）
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.
