Imaging mass spectrometry and genome mining via short sequence tagging identified the anti-infective agent arylomycin in Streptomyces roseosporus.
Imaging mass spectrometry and genome mining via short sequence tagging identified the anti-infective agent arylomycin in Streptomyces roseosporus.
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DOI：
10.1021/ja2040877
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发表时间：
2011-11-16
影响因子：
15
通讯作者：
Dorrestein, Pieter C.
中科院分区：
文献类型：
--
作者：
Liu, Wei-Ting;Kersten, Roland D.;Yang, Yu-Liang;Moore, Bradley S.;Dorrestein, Pieter C.
本文报道了在一株工业用达托霉素产生菌玫瑰孢链霉菌中发现的抗感染剂芳霉素及其生物合成基因簇。这是通过使用MALDI成像质谱（IMS）沿着肽基因组方法来实现的，其中我们已经扩展到本文所述的短序列标记（SST）。使用IMS，我们观察到在产生达托霉素之前，S.玫瑰孢菌，并与葡萄球菌细胞生长下降相关。进一步采用SST肽基因组学方法，该方法依赖于从串联质谱数据生成序列标签并查询基因组以鉴定生物合成基因，我们能够将这三种分子（1-3）鉴定为芳基霉素，芳基霉素是一类靶向I型信号肽酶的广谱抗生素。在S.然后鉴定玫瑰孢菌。从深入研究的微生物中鉴定芳霉素及其生物合成基因簇突出了IMS和MS指导的基因组挖掘方法在有效弥合表型、化学型和基因型之间的差距方面的优势。
Here, we described the discovery of anti-infective agent arylomycin and its biosynthetic gene cluster in an industrial daptomycin producing strain Streptomyces roseosporus. This was accomplished via the use of MALDI imaging mass spectrometry (IMS) along with peptidogenomic approach in which we have expanded to short sequence tagging (SST) described herein. Using IMS we have observed that prior to the production of daptomycin, a cluster of ions (1–3) were produced by S. roseosporus and correlated well with the decreased staphylococcal cell growth. Further adopted SST peptidogenomics approach, which relies on the generation of sequence tags from tandem mass spectrometric data and query against genomes to identify the biosynthetic genes, we were able to identify these three molecules (1–3) to arylomycins, a class of broad-spectrum antibiotics that targets type I signal peptidase. The gene cluster responsible for arylomycin production in S. roseosporus was then identified. The identification of arylomycins and their biosynthetic gene cluster from intensely studied microorganism highlights the strength of IMS and MS guided genome mining approaches in effectively bridging the gap between phenotypes, chemotypes and genotypes.
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DOI：
10.1073/pnas.1008368107
发表时间：
2010-09-14
影响因子：
11.1
作者：
Liu, Wei-Ting;Yang, Yu-Liang;Dorrestein, Pieter C.
通讯作者：
Dorrestein, Pieter C.
DOI：
10.1126/science.1176667
发表时间：
2009-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Fischbach MA;Walsh CT
通讯作者：
Walsh CT
影响因子：
2.8
作者：
Bockstael, Katrijn;Geukens, Nick;Van Aerschot, Arthur
通讯作者：
Van Aerschot, Arthur
影响因子：
4.8
作者：
Pylypenko, O;Vitali, F;Schlichting, I
通讯作者：
Schlichting, I
影响因子：
--
作者：
Imker HJ;Krahn D;Clerc J;Kaiser M;Walsh CT
通讯作者：
Walsh CT