Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, NY 10065.
Terrestrial Ecosystems Research Network, University of Adelaide, Adelaide, SA 5005, Australia.
Proc Natl Acad Sci U S A. 2017 Oct 31;114(44):11615-11620. doi: 10.1073/pnas.1710262114. Epub 2017 Oct 18.
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.
虽然细菌生物活性代谢产物一直是小分子治疗药物开发中小分子治疗药物的主要先导结构来源之一，但对于与自然环境中次级代谢变化相关的环境因素知之甚少。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程度、它在不同环境之间的变化情况，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，使用针对聚酮生物合成的酮合酶结构域或非核糖体肽生物合成的腺苷酸化结构域的引物扩增子的测序用于评估在澳大利亚大陆各地采集的土壤中的生物合成结构域组成和丰富度。使用在每个土壤点收集的环境变量，我们寻找与总体结构域丰富度或结构域组成变化相关的环境因素。在所测量的环境变量中，生物合成结构域组成的变化与纬度的变化最密切相关，与 pH 值的变化次之。尽管目前尚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，但从实际的角度来看，确定土壤宏基因组生物合成结构域组成差异的纬度基础应该有助于指导未来的天然产物发现工作。
