Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA, 92093, USA.
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA, 92093, USA.
Nat Commun. 2024 Jun 19;15(1):5230. doi: 10.1038/s41467-024-49367-x.
Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products. Applications across diverse marine habitats reveal biome-specific metabolomic signatures and levels of chemical diversity in concordance with sequence-based predictions. Expanded deployments, in situ cultivation, and metagenomics facilitate compound discovery, enhance yields, and link compounds to candidate producing organisms, although microbial community complexity creates challenges for the later. This compound-first approach to natural product discovery provides access to poorly explored chemical space and has implications for drug discovery and the detection of chemically mediated biotic interactions.
基于培养的微生物天然产物发现策略未能实现对地球微生物组中检测到的非凡生物合成潜力的挖掘。在这里，我们介绍了小分子原位树脂捕获（SMIRC）技术，这是一种无需培养即可从其产生的环境中直接获得天然产物的方法。我们使用 SMIRC 捕获了许多化合物，包括两种新的碳骨架，它们通过 NMR 进行了表征，并且包含了在我们的知识范围内，在天然产物中前所未有的结构特征。在不同的海洋生境中的应用揭示了生物群特异性的代谢组学特征和与基于序列的预测一致的化学多样性水平。扩展部署、原位培养和宏基因组学有助于化合物的发现、提高产量，并将化合物与候选产生生物联系起来，尽管微生物群落的复杂性给后期工作带来了挑战。这种以化合物为先导的天然产物发现方法可以进入探索较少的化学空间，并对药物发现和化学介导的生物相互作用的检测具有重要意义。
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