Despite decades of cultivating microorganisms for use in drug discovery, few attempts have been made to measure the extent to which common cultivation techniques have accessed existing chemical space. Metagenomic studies have shown that cultivable bacteria represent a fraction of those that exist in the environment, and that uncultivated populations in sediment have genes that encode for a high diversity of novel natural product (NP) biosynthetic enzymes. Quantifying these genes in both sediment and cultivatable bacterial populations allows us to assess how much diversity is present on nutrient agar and is critical to guiding the trajectory of future NP discovery platforms. Herein, we employed next-generation amplicon sequencing to assess the NP biosynthetic gene populations present in two Lake Huron sediment samples, and compared these with populations from their corresponding cultivatable bacteria. We highlight three findings from our study: (1) after cultivation, we recovered between 7.7% and 23% of three common types of NP biosynthetic genes from the original sediment population; (2) between 76.3% and 91.5% of measured NP biosynthetic genes from nutrient agar have yet to be characterized in known biosynthetic gene cluster databases, indicating that readily cultivatable bacteria harbor the potential to produce new NPs; and (3) even though the predominant taxa present on nutrient media represented some of the major producers of bacterial NPs, the sediment harbored a significantly greater pool of NP biosynthetic genes that could be mined for structural novelty, and these likely belong to taxa that typically have not been represented in microbial drug discovery libraries.

中文翻译：

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评估栽培技术从沉积物中恢复天然产物生物合成基因种群的效率

尽管培养了用于药物发现的微生物数十年，但很少有人尝试测量常见的培养技术进入现有化学空间的程度。元基因组学研究表明，可培养细菌仅占环境中细菌的一小部分，未沉积物的沉积物种群中的基因编码的新型天然产物（NP）生物合成酶的多样性很高。定量分析沉积物和可培养细菌种群中的这些基因，使我们能够评估营养琼脂上存在多少多样性，这对于指导未来NP发现平台的发展轨迹至关重要。在这里，我们采用了下一代扩增子测序来评估两个休伦湖沉积物样品中存在的NP生物合成基因种群，并将其与来自其相应可培养细菌的种群进行比较。我们着重从研究中得出三个发现：（1）培养后，我们从原始沉积物种群中恢复了三种常见类型的NP生物合成基因的7.7％至23％；（2）来自营养琼脂的76.3％至91.5％的已测NP生物合成基因尚未在已知的生物合成基因簇数据库中表征，这表明易于培养的细菌具有产生新NP的潜力；（3）尽管营养培养基上存在的主要分类单元代表了细菌NP的一些主要产生者，但沉积物中仍蕴藏着大量的NP生物合成基因，可用于结构新颖性的挖掘，