Department of Pharmaceutical Sciences, Center for Biomolecular Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60607, United States.
German Centre for Infection Research (DZIF), Interfaculty Institute of Microbiology and Infection Medicine Tübingen, University of Tübingen, Auf der Morgenstelle 28, Tübingen 72076, Germany.
ACS Chem Biol. 2021 Nov 19;16(11):2623-2631. doi: 10.1021/acschembio.1c00653. Epub 2021 Oct 4.
Environmental microorganisms continue to serve as a major source of bioactive natural products (NPs) and as an inspiration for many other scaffolds in the toolbox of modern medicine. Nearly all microbial NP-inspired therapies can be traced to field expeditions to collect samples from the environment. Despite the importance of these expeditions in the search for new drugs, few studies have attempted to document the extent to which NPs or their corresponding production genes are distributed within a given environment. To gain insights into this, the geographic occurrence of NP ketosynthase (KS) and adenylation (A) domains was documented across 53 and 58 surface sediment samples, respectively, covering 59,590 square kilometers of Lake Huron. Overall, no discernible NP geographic distribution patterns were observed for 90,528 NP classes of nonribosomal peptides and polyketides detected in the survey. While each sampling location harbored a similar number of A domain operational biosynthetic units (OBUs), a limited overlap of OBU type was observed, suggesting that at the sequencing depth used in this study, no single location served as a NP "hotspot". These data support the hypothesis that there is ample variation in NP occurrence between sampling sites and suggest that extensive sample collection efforts are required to fully capture the functional chemical diversity of sediment microbial communities on a regional scale.
环境微生物仍然是生物活性天然产物 (NPs) 的主要来源,也是现代医学工具包中许多其他支架的灵感来源。几乎所有受微生物 NP 启发的治疗方法都可以追溯到从环境中收集样本的实地考察。尽管这些考察对于寻找新药非常重要,但很少有研究试图记录给定环境中 NP 或其相应生产基因的分布程度。为了深入了解这一点,分别在 53 个和 58 个表层沉积物样本中记录了 NP 酮合酶 (KS) 和腺苷酸化 (A) 结构域的地理发生情况,涵盖了休伦湖 59590 平方公里的面积。总的来说,在所调查的非核糖体肽和聚酮类 90528 种 NP 类中,没有观察到明显的 NP 地理分布模式。虽然每个采样点都含有相似数量的 A 结构域操作生物合成单元 (OBU),但观察到 OBU 类型的有限重叠,表明在本研究中使用的测序深度下,没有一个单一的地点是 NP 的“热点”。这些数据支持了这样一种假设,即在采样点之间 NP 的出现存在很大的差异,并表明需要进行广泛的样本采集工作,才能在区域尺度上充分捕获沉积物微生物群落的功能化学多样性。