An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.
An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products.
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DOI：
10.1038/ncomms9421
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发表时间：
2015-09-28
影响因子：
16.6
通讯作者：
Magarvey NA
中科院分区：
文献类型：
--
作者：
Johnston CW;Skinnider MA;Wyatt MA;Li X;Ranieri MR;Yang L;Zechel DL;Ma B;Magarvey NA
细菌天然产物是一组多样而有价值的小分子，基因组测序表明绝大多数尚未发现。从生物合成装配线预测天然产物结构可以促进它们的发现，但需要高度自动化，准确和集成的系统来挖掘广谱的测序细菌基因组。在这里，我们提出了一个基因组引导的天然产物发现工具，自动预测，combinatorialize和识别聚酮化合物和非核糖体肽的生物合成装配线使用LC-MS/MS数据的粗提取物在高通量的方式。我们详细介绍了直接识别和分离的六个遗传预测聚酮和非核糖体肽使用我们的基因组天然产物平台。这一高度自动化、用户友好的程序提供了一种实现基因编码天然产品潜力的手段。 微生物天然产物代表了一个潜在的药物制剂的大水库。在此，约翰斯顿等人描述了一种计算机自动化程序，用于将基因组序列与鉴定和分离的天然产物连接起来。
Bacterial natural products are a diverse and valuable group of small molecules, and genome sequencing indicates that the vast majority remain undiscovered. The prediction of natural product structures from biosynthetic assembly lines can facilitate their discovery, but highly automated, accurate, and integrated systems are required to mine the broad spectrum of sequenced bacterial genomes. Here we present a genome-guided natural products discovery tool to automatically predict, combinatorialize and identify polyketides and nonribosomal peptides from biosynthetic assembly lines using LC–MS/MS data of crude extracts in a high-throughput manner. We detail the directed identification and isolation of six genetically predicted polyketides and nonribosomal peptides using our Genome-to-Natural Products platform. This highly automated, user-friendly programme provides a means of realizing the potential of genetically encoded natural products. Microbial natural products represent a large reservoir of potential pharmaceutical agents. Here, Johnston et al. describe a computer-automated programme for connecting genome sequences with identified and isolated natural products.