Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, California, USA.
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
Appl Environ Microbiol. 2019 Apr 4;85(8). doi: 10.1128/AEM.02830-18. Print 2019 Apr 15.
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 , 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 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. 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.
已经从培养的微生物中鉴定出数千种天然产物，但在环境中证明它们的存在却一直难以捉摸。质谱技术的进步，结合公共数据库，现在使得通过直接从环境样本中检测化合物来解决这种差异成为可能。在这里，我们使用吸附树脂、串联质谱和下一代测序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道的天然产物，为它们是在环境中产生的提供了证据，以及人为来源的化合物，表明这种方法可以用作环境影响的指标。细菌代谢产物司替戊醇被定量，并显示出达到生理相关浓度，表明它可能影响沉积物群落结构。司替戊醇浓度与产生司替戊醇的细菌属的相对丰度相关，并且在从同一地点培养的菌株中得到了证实，为化合物和候选生产者之间建立了联系。宏基因组分析揭示了许多与吲哚咔唑生物合成相关的生物合成基因簇，为司替戊醇的非典型来源提供了证据，并为评估天然产物与产生它们的生物体之间的关系提供了途径。非靶向环境代谢组学避免了实验室培养的需要，代表了一种很有前途的方法，可以了解天然产物在塑造海洋沉积物中微生物群落结构方面的功能作用。天然产物很容易从培养的细菌中分离出来，并被用于有用的目的，包括药物发现。然而，这些化合物在它们被获得的环境中很少被检测到，从而限制了我们对它们生态意义的理解。在这里，我们使用环境代谢组学直接评估海洋沉积物中的化学多样性。我们鉴定了许多代谢物，在一种情况下，还分离出了能够产生检测到的一种化合物的细菌菌株。将环境代谢组学与群落和宏基因组分析相结合，为化合物和生产者的联系提供了机会，并开始评估海洋沉积物中特殊代谢物介导的复杂相互作用。
