Computational approaches to natural product discovery.

Computational approaches to natural product discovery.
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DOI:
10.1038/nchembio.1884
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发表时间:
2015-09
影响因子:
14.8
通讯作者:
Fischbach, Michael A.
Fischbach, Michael A.
中科院分区:
生物学1区
文献类型:
--
作者:
Medema, Marnix H.;Fischbach, Michael A.

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从最早的链霉菌基因组序列开始,天然产物基因组挖掘的前景就一直令人着迷:基因组学和生物信息学将把化合物发现从临时追求转变为高通量努力。然而,直到最近,基因组挖掘对天然产品的发现只起到了一定的促进作用。在这里,我们认为挖掘不断增长的(元)基因组数据的算法的发展将使基因组挖掘的前景成为现实。我们回顾了已经开发的用于识别基因组序列中的生物合成基因簇并预测其产物的化学结构的计算策略。然后我们讨论联网策略,可以系统化大量的遗传和化学数据,并将基因组信息与新陈代谢和表型数据联系起来。最后,我们提供了未来天然产品发现可能是什么样子的愿景,特别是考虑了微生物生态学中关于代谢物在物种间相互作用中的作用的长期存在的问题。
From the earliest Streptomyces genome sequences, the promise of natural product genome mining has been captivating: genomics and bioinformatics would transform compound discovery from an ad hoc pursuit to a high-throughput endeavor. Until recently, however, genome mining has advanced natural product discovery only modestly. Here, we argue that the development of algorithms to mine the continuously increasing amounts of (meta)genomic data will enable the promise of genome mining to be realized. We review computational strategies that have been developed to identify biosynthetic gene clusters in genome sequences and predict the chemical structures of their products. We then discuss networking strategies that can systematize large volumes of genetic and chemical data, and connect genomic information to metabolomic and phenotypic data. Finally, we provide a vision of what natural product discovery might look like in the future, specifically considering long-standing questions in microbial ecology regarding the roles of metabolites in interspecies interactions.
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