Prioritizing Natural Product Diversity in a Collection of 146 Bacterial Strains Based on Growth and Extraction Protocols.
Prioritizing Natural Product Diversity in a Collection of 146 Bacterial Strains Based on Growth and Extraction Protocols.
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DOI：
10.1021/acs.jnatprod.6b00722
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发表时间：
2017-03-24
影响因子：
5.1
通讯作者：
Moore BS
中科院分区：
文献类型：
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作者：
Crüsemann M;O'Neill EC;Larson CB;Melnik AV;Floros DJ;da Silva RR;Jensen PR;Dorrestein PC;Moore BS
为了加速新型特殊代谢物的快速高效发现和分离，同时尽量减少在已知化合物重新发现上的资源浪费，开发用于菌株优先级排序、快速去重复以及评估有利的培养和提取条件的有效方法至关重要。在此，我们通过液相色谱 - 串联质谱（LC - MS/MS）分析系统地评估培养和提取参数，并随后通过全球天然产物社会分子网络（GNPS）平台进行去重复，从而对细菌菌株进行研究。所开发的方法快速，所需时间和样品材料极少，并且与高通量提取物分析兼容，从而简化了菌株优先级排序和培养参数的评估。通过这种方法，我们分析了146株海洋盐孢菌属（Salinispora）和链霉菌属（Streptomyces）菌株，这些菌株使用多种不同的方案进行培养和提取。总共分析了603个样品，产生了大约180万个质谱。我们构建了一个全面的分子网络，并鉴定出15个不同天然产物及其类似物的分子家族。在比较生长和提取条件时，该网络的规模和广度显示出分子多样性方面具有统计学支持的趋势。该网络对菌株集合的生物合成能力进行了广泛的调查，并提供了一种基于代谢物的多样性和新颖性比较菌株的方法。这种方法使我们能够快速识别代谢物产生的模式，这些模式可与分类学、培养条件和提取方法相关联，并为最有价值的生长和提取条件提供信息。
In order to expedite the rapid and efficient discovery and isolation of novel specialized metabolites, whilst minimizing the waste of resources on rediscovery of known compounds, it is crucial to develop efficient approaches for strain prioritization, rapid dereplication, and the assessment of favored cultivation and extraction conditions. Herein we interrogated bacterial strains by systematically evaluating cultivation and extraction parameters with LC-MS/MS analysis and subsequent dereplication through the Global Natural Product Social Molecular Networking (GNPS) platform. The developed method is fast, requiring minimal time and sample material, and is compatible with high throughput extract analysis, thereby streamlining strain prioritization and evaluation of culturing parameters. With this approach, we analyzed 146 marine Salinispora and Streptomyces strains that were grown and extracted using multiple different protocols. In total, 603 samples were analyzed, generating approximately 1.8 million mass spectra. We constructed a comprehensive molecular network and identified 15 molecular families of diverse natural products and their analogues. The size and breadth of this network shows statistically supported trends in molecular diversity when comparing growth and extraction conditions. The network provides an extensive survey of the biosynthetic capacity of the strain collection and a method to compare strains based on the variety and novelty of their metabolites. This approach allows us to quickly identify patterns in metabolite production that can be linked to taxonomy, culture conditions, and extraction methods, as well as informing the most valuable growth and extraction conditions.