Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.
Pep2Path: automated mass spectrometry-guided genome mining of peptidic natural products.
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DOI：
10.1371/journal.pcbi.1003822
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发表时间：
2014-09
影响因子：
4.3
通讯作者：
Breitling R
中科院分区：
文献类型：
--
作者：
Medema MH;Paalvast Y;Nguyen DD;Melnik A;Dorrestein PC;Takano E;Breitling R
非核糖体和核糖体合成的生物活性多肽构成了具有重要生物医学意义的分子的来源，包括抗生素(如青霉素)、免疫抑制剂(如环孢菌素)和细胞抑制剂(如博莱霉素)。最近，一种创新的基于质谱学的策略，即肽基因组学，已经被率先用于有效地从微生物菌株中挖掘出新的肽类代谢物。尽管质谱肽检测可以非常快速地进行，但真正的高通量天然产物发现方法仍然受到无法快速将鉴定的串联质谱图与负责相应化合物的生物合成的基因簇相匹配的限制。通过Pep2Path，我们推出了一个软件包，通过将质谱图与其相应的生物合成基因簇进行快速贝叶斯概率匹配，实现肽基因组学方法的完全自动化。对该方法的详细基准测试表明，该方法足以正确识别基因簇，即使在由数百个基因组组成的数据集中也是如此，这也使得将来自未测序生物的化合物与其他基因组中密切相关的生物合成基因簇进行匹配成为可能。将Pep2Path应用于一个未知生物合成路线的化合物数据集，我们能够识别出五个重要化合物生物合成的候选基因簇。值得注意的是，在变形杆菌亚门的基因组中检测到了其中的一个，而不是最初鉴定的分子。总而言之，我们的方法为高通量发现新肽类天然产品铺平了道路。Pep2Path可以从用PYTHON实现的http://pep2path.sourceforge.net/，免费获得，按照GNU通用公共许可证v3许可，并在MS Windows、Linux和MacOSX上受支持。
Nonribosomally and ribosomally synthesized bioactive peptides constitute a source of molecules of great biomedical importance, including antibiotics such as penicillin, immunosuppressants such as cyclosporine, and cytostatics such as bleomycin. Recently, an innovative mass-spectrometry-based strategy, peptidogenomics, has been pioneered to effectively mine microbial strains for novel peptidic metabolites. Even though mass-spectrometric peptide detection can be performed quite fast, true high-throughput natural product discovery approaches have still been limited by the inability to rapidly match the identified tandem mass spectra to the gene clusters responsible for the biosynthesis of the corresponding compounds. With Pep2Path, we introduce a software package to fully automate the peptidogenomics approach through the rapid Bayesian probabilistic matching of mass spectra to their corresponding biosynthetic gene clusters. Detailed benchmarking of the method shows that the approach is powerful enough to correctly identify gene clusters even in data sets that consist of hundreds of genomes, which also makes it possible to match compounds from unsequenced organisms to closely related biosynthetic gene clusters in other genomes. Applying Pep2Path to a data set of compounds without known biosynthesis routes, we were able to identify candidate gene clusters for the biosynthesis of five important compounds. Notably, one of these clusters was detected in a genome from a different subphylum of Proteobacteria than that in which the molecule had first been identified. All in all, our approach paves the way towards high-throughput discovery of novel peptidic natural products. Pep2Path is freely available from http://pep2path.sourceforge.net/, implemented in Python, licensed under the GNU General Public License v3 and supported on MS Windows, Linux and Mac OS X.
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影响因子：
--
作者：
Guthals A;Watrous JD;Dorrestein PC;Bandeira N
通讯作者：
Bandeira N
影响因子：
14.9
作者：
de Jong A;van Heel AJ;Kok J;Kuipers OP
通讯作者：
Kuipers OP
影响因子：
14.9
作者：
Blin K;Medema MH;Kazempour D;Fischbach MA;Breitling R;Takano E;Weber T
通讯作者：
Weber T
影响因子：
14.9
作者：
de Jong A;van Hijum SA;Bijlsma JJ;Kok J;Kuipers OP
通讯作者：
Kuipers OP
影响因子：
4.2
作者：
Roach, Patrick J.;Laskin, Julia;Laskin, Alexander
通讯作者：
Laskin, Alexander