Duncan Katherine R, Crüsemann Max, Lechner Anna, Sarkar Anindita, Li Jie, Ziemert Nadine, Wang Mingxun, Bandeira Nuno, Moore Bradley S, Dorrestein Pieter C, Jensen Paul R
Center for Marine Biotechnology & Biomedicine, Scripps Institution of Oceanography, University of California San Diego, La Jolla, CA 92093, USA.
Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA 92093, USA.
Chem Biol. 2015 Apr 23;22(4):460-471. doi: 10.1016/j.chembiol.2015.03.010. Epub 2015 Apr 9.
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.
基因组测序显示，细菌中含有的生物合成基因簇比根据迄今发现的次级代谢产物数量预测的要多得多。虽然这种生物合成库激发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存在差距。在这里，我们将分子网络和基于模式的基因组挖掘这一新概念应用于35株盐孢菌菌株，其中包括30株本研究可获取或已获得基因组草图序列的菌株。结果提供了一种同时比较大量复杂微生物提取物的方法，这有助于鉴定培养基成分、已知化合物及其衍生物，以及可优先进行结构解析的新化合物。这些研究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，其中通过基于模式的生物信息学方法对喹霉素型缩肽雷替霉素A进行了表征，并将其与基因簇NRPS40联系起来。
