Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.
Bacterial natural product biosynthetic domain composition in soil correlates with changes in latitude on a continent-wide scale.
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DOI：
10.1073/pnas.1710262114
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发表时间：
2017-10-31
影响因子：
11.1
通讯作者：
Brady, Sean F
中科院分区：
文献类型：
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作者：
Lemetre, Christophe;Maniko, Jeffrey;Brady, Sean F
虽然细菌的生物活性代谢物一直是最丰富的来源之一的铅结构的小分子治疗的发展，很少有人知道的环境因素与变化的次生代谢在整个自然环境。环境微生物组的大规模测序有可能揭示隐藏在环境中的细菌生物合成多样性的丰富性，它如何从一个环境到下一个环境变化，以及哪些环境因素与生物合成多样性的变化相关。在这项研究中，使用引物靶向聚酮生物合成或腺苷酸化结构域从非核糖体肽生物合成的酮合酶域产生的PCR扩增子的测序被用来评估生物合成结构域的组成和丰富的土壤中收集在澳大利亚大陆。使用在每个土壤站点收集的环境变量，我们寻找与高的整体域丰富度或域组成的变化相关的环境因素。在我们测量的环境变量中，生物合成结构域组成的变化与纬度的变化最密切相关，在较小程度上与pH值的变化相关。尽管目前还不清楚可能驱动生物合成结构域组成与纬度之间关系的确切因素组合，从实践的角度来看，确定土壤宏基因组生物合成结构域组成差异的纬度基础，未来的天然产物发现工作。
Although bacterial bioactive metabolites have been one of the most prolific sources of lead structures for the development of small-molecule therapeutics, very little is known about the environmental factors associated with changes in secondary metabolism across natural environments. Large-scale sequencing of environmental microbiomes has the potential to shed light on the richness of bacterial biosynthetic diversity hidden in the environment, how it varies from one environment to the next, and what environmental factors correlate with changes in biosynthetic diversity. In this study, the sequencing of PCR amplicons generated using primers targeting either ketosynthase domains from polyketide biosynthesis or adenylation domains from nonribosomal peptide biosynthesis was used to assess biosynthetic domain composition and richness in soils collected across the Australian continent. Using environmental variables collected at each soil site, we looked for environmental factors that correlated with either high overall domain richness or changes in the domain composition. Among the environmental variables we measured, changes in biosynthetic domain composition correlate most closely with changes in latitude and to a lesser extent changes in pH. Although it is unclear at this time the exact mix of factors that may drive the relationship between biosynthetic domain composition and latitude, from a practical perspective the identification of a latitudinal basis for differences in soil metagenome biosynthetic domain compositions should help guide future natural product discovery efforts.