Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity,Angewandte Chemie International Edition

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Crowdsourcing Natural Products Discovery to Access Uncharted Dimensions of Fungal Metabolite Diversity
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2013-11-27 , DOI: 10.1002/anie.201306549
Lin Du ₁ , Andrew J Robles , Jarrod B King , Douglas R Powell , Andrew N Miller , Susan L Mooberry , Robert H Cichewicz

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A fundamental component for success in drug discovery is the ability to assemble and screen compounds that encompass a broad swath of biologically relevant chemical‐diversity space. Achieving this goal in a natural‐products‐based setting requires access to a wide range of biologically diverse specimens. For this reason, we introduced a crowdsourcing program in which citizen scientists furnish soil samples from which new microbial isolates are procured. Illustrating the strength of this approach, we obtained a unique fungal metabolite, maximiscin, from a crowdsourced Alaskan soil sample. Maximiscin, which exhibits a putative combination of polyketide synthase (PKS), non‐ribosomal peptide synthetase (NRPS), and shikimate pathway components, was identified as an inhibitor of UACC‐62 melanoma cells (LC50=0.93 μM). The metabolite also exhibited efficacy in a xenograft mouse model. These results underscore the value of building cooperative relationships between research teams and citizen scientists to enrich drug discovery efforts.

中文翻译：

众包天然产品发现，了解真菌代谢物多样性的未知维度

药物发现成功的一个基本要素是能够组装和筛选涵盖广泛的生物相关化学多样性空间的化合物。在基于天然产品的环境中实现这一目标需要获得广泛的生物多样性样本。因此，我们推出了一项众包计划，公民科学家提供土壤样本，从中采购新的微生物分离株。为了说明这种方法的优势，我们从众包的阿拉斯加土壤样本中获得了一种独特的真菌代谢物 maximiscin。 Maximiscin 假定是聚酮合酶 (PKS)、非核糖体肽合成酶 (NRPS) 和莽草酸途径成分的组合，被鉴定为 UACC-62 黑色素瘤细胞的抑制剂 (LC50=0.93 μM )。该代谢物还在异种移植小鼠模型中表现出功效。这些结果强调了在研究团队和公民科学家之间建立合作关系以丰富药物发现工作的价值。

更新日期：2013-11-27

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