Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM).
Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM).
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DOI：
10.1093/nar/gkv1012
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发表时间：
2015-11-16
影响因子：
14.9
通讯作者：
Magarvey NA
中科院分区：
文献类型：
--
作者：
Skinnider MA;Dejong CA;Rees PN;Johnston CW;Li H;Webster AL;Wyatt MA;Magarvey NA
微生物天然产物是进化的生物活性小分子和药物的宝贵来源。下一代和宏基因组测序表明基因组潜力尚未开发，但已知代谢物的高重新发现率越来越阻碍传统的天然产物筛选计划。因此，将生物合成基因簇连接到新型化学支架的新方法对于有针对性地发现基因编码的天然产物至关重要。在这里，我们展示了 PRISM，一种计算资源，用于识别生物合成基因簇、预测遗传编码的非核糖体肽以及 I 型和 II 型聚酮化合物，以及已知天然产物的生物和化学信息去复制。 PRISM 采用新颖的算法，使其能够独特地预测 II 型聚酮化合物、脱氧糖和起始单元，使其成为全面的基因组引导化学结构预测引擎。当多个潜在底物与生物合成逻辑一致时，可利用包含 57 个剪裁反应的库来生成组合支架库。我们将 PRISM 的准确性与现有基因组分析平台进行比较。 PRISM 是一个开源、用户友好的 Web 应用程序，可在 http://magarveylab.ca/prism/ 上获取。
Microbial natural products are an invaluable source of evolved bioactive small molecules and pharmaceutical agents. Next-generation and metagenomic sequencing indicates untapped genomic potential, yet high rediscovery rates of known metabolites increasingly frustrate conventional natural product screening programs. New methods to connect biosynthetic gene clusters to novel chemical scaffolds are therefore critical to enable the targeted discovery of genetically encoded natural products. Here, we present PRISM, a computational resource for the identification of biosynthetic gene clusters, prediction of genetically encoded nonribosomal peptides and type I and II polyketides, and bio- and cheminformatic dereplication of known natural products. PRISM implements novel algorithms which render it uniquely capable of predicting type II polyketides, deoxygenated sugars, and starter units, making it a comprehensive genome-guided chemical structure prediction engine. A library of 57 tailoring reactions is leveraged for combinatorial scaffold library generation when multiple potential substrates are consistent with biosynthetic logic. We compare the accuracy of PRISM to existing genomic analysis platforms. PRISM is an open-source, user-friendly web application available at http://magarveylab.ca/prism/.