新しい創薬手法で海洋化合物の宝庫を解き明かす可能性(New Drug Discovery Technique May Unlock Trove of Marine Compounds)

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2024-08-13 カリフォルニア大学サンディエゴ校(UCSD)

サンディエゴの研究者たちは、新しい手法「SMIRC」を開発し、海中で化合物を直接捕獲して新薬や製品の開発に役立てることができるようになりました。この方法により、がん細胞への効果や心臓機能への影響が期待される新しい化合物が発見されました。SMIRCは、従来の微生物培養による手法に比べ、効率的に新たな化合物を特定できるため、新薬開発の加速に寄与する可能性があります。

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低分子の直接樹脂捕捉が天然物発見に化合物ファーストのアプローチを提供す Small molecule in situ resin capture provides a compound first approach to natural product discovery

Alexander Bogdanov,Mariam N. Salib,Alexander B. Chase,Heinz Hammerlindl,Mitchell N. Muskat,Stephanie Luedtke,Elany Barbosa da Silva,Anthony J. O’Donoghue,Lani F. Wu,Steven J. Altschuler,Tadeusz F. Molinski & Paul R. Jensen

Nature Communications  Published:19 June 2024

DOI:https://doi.org/10.1038/s41467-024-49367-x

新しい創薬手法で海洋化合物の宝庫を解き明かす可能性(New Drug Discovery Technique May Unlock Trove of Marine Compounds)

Abstract

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.

有機化学・薬学
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