In soil ecosystems, microorganisms produce diverse secondary metabolites such as antibiotics, antifungals and siderophores that mediate communication, competition and interactions with other organisms and the environment1,2. Most known antibiotics are derived from a few culturable microbial taxa3, and the biosynthetic potential of the vast majority of bacteria in soil has rarely been investigated4. Here we reconstruct hundreds of near-complete genomes from grassland soil metagenomes and identify microorganisms from previously understudied phyla that encode diverse polyketide and nonribosomal peptide biosynthetic gene clusters that are divergent from well-studied clusters. These biosynthetic loci are encoded by newly identified members of the Acidobacteria, Verrucomicobia and Gemmatimonadetes, and the candidate phylum Rokubacteria. Bacteria from these groups are highly abundant in soils5–7, but have not previously been genomically linked to secondary metabolite production with confidence. In particular, large numbers of biosynthetic genes were characterized in newly identified members of the Acidobacteria, which is the most abundant bacterial phylum across soil biomes5. We identify two acidobacterial genomes from divergent lineages, each of which encodes an unusually large repertoire of biosynthetic genes with up to fifteen large polyketide and nonribosomal peptide biosynthetic loci per genome. To track gene expression of genes encoding polyketide synthases and nonribosomal peptide synthetases in the soil ecosystem that we studied, we sampled 120 time points in a microcosm manipulation experiment and, using metatranscriptomics, found that gene clusters were differentially co-expressed in response to environmental perturbations. Transcriptional co-expression networks for specific organisms associated biosynthetic genes with two-component systems, transcriptional activation, putative antimicrobial resistance and iron regulation, linking metabolite biosynthesis to processes of environmental sensing and ecological competition. We conclude that the biosynthetic potential of abundant and phylogenetically diverse soil microorganisms has previously been underestimated. These organisms may represent a source of natural products that can address needs for new antibiotics and other pharmaceutical compounds.Metagenomic and soil microcosm analyses identify abundant biosynthetic gene clusters in genomes of microorganisms from a northern Californian grassland ecosystem that provide a potential source for the future development of bacterial natural products.

中文翻译：

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新型土壤细菌具有多种次生代谢物生物合成基因

在土壤生态系统中，微生物会产生多种次生代谢物，例如抗生素、抗真菌剂和铁载体，它们可以调节与其他生物体和环境的交流、竞争和相互作用 1,2。大多数已知的抗生素来自少数可培养的微生物分类群 3，并且很少研究土壤中绝大多数细菌的生物合成潜力 4。在这里，我们从草地土壤宏基因组中重建了数百个近乎完整的基因组，并从先前研究不足的门中识别出微生物，这些微生物编码多种聚酮化合物和非核糖体肽生物合成基因簇，这些基因簇与经过充分研究的簇不同。这些生物合成基因座由新发现的酸杆菌属、疣孢菌属和 Gemmatimonadetes 成员以及候选门 Rokubacteria 编码。来自这些组的细菌在土壤中非常丰富 5-7，但以前没有信心十足地在基因组上与次生代谢物的产生相关联。特别是，大量生物合成基因在新发现的酸杆菌成员中得到表征，酸杆菌是土壤生物群落中最丰富的细菌门 5。我们从不同的谱系中识别出两个酸杆菌基因组，每个基因组都编码一个异常大的生物合成基因库，每个基因组有多达 15 个大聚酮​​化合物和非核糖体肽生物合成基因座。为了跟踪我们研究的土壤生态系统中编码聚酮化合物合酶和非核糖体肽合成酶的基因的基因表达，我们在微观操作实验中对 120 个时间点进行了采样，并使用宏转录组学，发现基因簇在响应环境扰动时有差异地共表达。特定生物体的转录共表达网络与双组分系统、转录激活、假定的抗菌素耐药性和铁调节相关的生物合成基因，将代谢物生物合成与环境传感和生态竞争过程联系起来。我们得出的结论是，先前低估了丰富且系统发育多样的土壤微生物的生物合成潜力。这些生物体可能是天然产物的来源，可以满足对新抗生素和其他药物化合物的需求。