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Detection of Natural Products and Their Producers in Ocean Sediments

机译：海洋沉积物中天然产物及其生产者的检测

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Thousands of natural products have been identified from cultured microorganisms, yet evidence of their production in the environment has proven elusive. Technological advances in mass spectrometry, combined with public databases, now make it possible to address this disparity by detecting compounds directly from environmental samples. Here, we used adsorbent resins, tandem mass spectrometry, and next-generation sequencing to assess the metabolome of marine sediments and its relationship to bacterial community structure. We identified natural products previously reported from cultured bacteria, providing evidence they are produced in situ, and compounds of anthropogenic origin, suggesting this approach can be used as an indicator of environmental impact. The bacterial metabolite staurosporine was quantified and shown to reach physiologically relevant concentrations, indicating that it may influence sediment community structure. Staurosporine concentrations were correlated with the relative abundance of the staurosporine-producing bacterial genus Salinispora and production confirmed in strains cultured from the same location, providing a link between compound and candidate producer. Metagenomic analyses revealed numerous biosynthetic gene clusters related to indolocarbazole biosynthesis, providing evidence for noncanonical sources of staurosporine and a path forward to assess the relationships between natural products and the organisms that produce them. Untargeted environmental metabolomics circumvents the need for laboratory cultivation and represents a promising approach to understanding the functional roles of natural products in shaping microbial community structure in marine sediments.IMPORTANCE Natural products are readily isolated from cultured bacteria and exploited for useful purposes, including drug discovery. However, these compounds are rarely detected in the environments from which the bacteria are obtained, thus limiting our understanding of their ecological significance. Here, we used environmental metabolomics to directly assess chemical diversity in marine sediments. We identified numerous metabolites and, in one case, isolated strains of bacteria capable of producing one of the compounds detected. Coupling environmental metabolomics with community and metagenomic analyses provides opportunities to link compounds and producers and begin to assess the complex interactions mediated by specialized metabolites in marine sediments.
机译：从培养的微生物中已经鉴定出成千上万的天然产物，但是在环境中生产这些产物的证据已被证明难以捉摸。质谱技术的进步与公共数据库相结合，使得通过直接从环境样品中检测化合物来解决这一差距成为可能。在这里，我们使用了吸附树脂，串联质谱和下一代测序技术来评估海洋沉积物的代谢组及其与细菌群落结构的关系。我们鉴定了以前从培养细菌中报告的天然产物，提供了它们是就地产生的证据，以及人为来源的化合物，这表明该方法可以用作环境影响的指标。细菌代谢物星形孢菌素被定量并显示达到生理相关浓度，表明它可能影响沉积物群落结构。星形孢菌素的浓度与产生星形孢菌素的细菌Salinispora的相对丰度相关，并在同一位置培养的菌株中证实了其产生，从而提供了化合物与候选生产者之间的联系。元基因组学分析揭示了许多与吲哚并咔唑生物合成有关的生物合成基因簇，为星形孢菌素的非规范来源提供了证据，并为评估天然产物与生产它们的生物之间的关系提供了一条途径。非目标环境代谢物组学无需实验室培养，是了解天然产物在塑造海洋沉积物中微生物群落结构中的功能的有前途的方法。重要信息天然产物易于从培养的细菌中分离出来，并用于包括药物发现在内的有用目的。但是，这些化合物很少在获得细菌的环境中检测到，因此限制了我们对它们的生态意义的理解。在这里，我们使用环境代谢组学直接评估了海洋沉积物中的化学多样性。我们鉴定了许多代谢产物，在一种情况下，鉴定出了能够产生一种所检测化合物的分离菌株。环境代谢组学与社区和宏基因组学分析的耦合提供了将化合物与生产者联系起来并开始评估由海洋沉积物中的专门代谢物介导的复杂相互作用的机会。

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