Molecular networking and pattern-based genome mining improves discovery of biosynthetic gene clusters and their products from Salinispora species.

Molecular networking and pattern-based genome mining improves discovery of biosynthetic gene clusters and their products from Salinispora species.
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DOI:
10.1016/j.chembiol.2015.03.010
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发表时间:
2015-04-23
影响因子:
--
通讯作者:
Jensen PR
Jensen PR
中科院分区:
生物1区
文献类型:
--
作者:
Duncan KR;Crüsemann M;Lechner A;Sarkar A;Li J;Ziemert N;Wang M;Bandeira N;Moore BS;Dorrestein PC;Jensen PR

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基因组测序显示,细菌包含的生物合成基因簇比基于迄今发现的次级代谢产物数量所预测的要多得多。虽然这种生物合成的水库已经培养了人们对天然产物发现新工具的兴趣,但基因簇检测和化合物发现之间仍然存在差距。在这里,我们应用分子网络和基于模式的基因组挖掘的新概念,35 Salinispora菌株,包括30个基因组序列草案,可用于本研究或获得。结果提供了一种方法,同时比较了大量的复杂的微生物提取物,这有利于识别介质成分,已知的化合物及其衍生物,以及新的化合物,可以优先进行结构解析。这些努力揭示了相当大的代谢物多样性,并导致了几个分子家族基因簇配对,其中奎诺霉素型缩肽瑞替霉素A的特点和连接到基因簇NRPS40使用模式为基础的生物信息学方法。
Genome sequencing has revealed that bacteria contain many more biosynthetic gene clusters than predicted based on the number of secondary metabolites discovered to date. While this biosynthetic reservoir has fostered interest in new tools for natural product discovery, there remains a gap between gene cluster detection and compound discovery. Here we apply molecular networking and the new concept of pattern-based genome mining to 35 Salinispora strains including 30 for which draft genome sequences were either available or obtained for this study. The results provide a method to simultaneously compare large numbers of complex microbial extracts, which facilitated the identification of media components, known compounds and their derivatives, and new compounds that could be prioritized for structure elucidation. These efforts revealed considerable metabolite diversity and led to several molecular family-gene cluster pairings, of which the quinomycin-type depsipeptide retimycin A was characterized and linked to gene cluster NRPS40 using pattern-based bioinformatic approaches.
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