Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093, Unites States.
J Am Chem Soc. 2011 Nov 16;133(45):18010-3. doi: 10.1021/ja2040877. Epub 2011 Oct 24.
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 observed that prior to the production of daptomycin, a cluster of ions (1-3) was produced by S. roseosporus and correlated well with the decreased staphylococcal cell growth. With a 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 target type I signal peptidase. The gene cluster was then identified. This highlights the strength of IMS and MS guided genome mining approaches in effectively bridging the gap between phenotypes, chemotypes, and genotypes.
在这里，我们描述了在工业生产达托霉素的玫瑰孢链霉菌中发现的抗感染剂arylomycin 及其生物合成基因簇。这是通过使用 MALDI 成像质谱 (IMS) 以及肽基因组学方法实现的，我们在此基础上扩展了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，玫瑰孢链霉菌会产生一簇离子 (1-3)，并且与金黄色葡萄球菌细胞生长减少密切相关。采用进一步的 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，并针对基因组进行查询以鉴定生物合成基因，我们能够将这三个分子 (1-3) 鉴定为 arylomycins，一类针对 I 型信号肽酶的广谱抗生素。然后鉴定了基因簇。这突显了 IMS 和 MS 引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差距方面的优势。
