Wu Changsheng, Du Chao, Gubbens Jacob, Choi Young Hae, van Wezel Gilles P
Leiden Institute of Chemistry, Leiden University , Einsteinweg 55, 2333 CC Leiden, The Netherlands.
J Nat Prod. 2015 Oct 23;78(10):2355-63. doi: 10.1021/acs.jnatprod.5b00276. Epub 2015 Oct 6.
Actinomycetes are a major source of antimicrobials, anticancer compounds, and other medically important products, and their genomes harbor extensive biosynthetic potential. Major challenges in the screening of these microorganisms are to activate the expression of cryptic biosynthetic gene clusters and the development of technologies for efficient dereplication of known molecules. Here we report the identification of a previously unidentified isatin-type antibiotic produced by Streptomyces sp. MBT28, following a strategy based on NMR-based metabolomics combined with the introduction of streptomycin resistance in the producer strain. NMR-guided isolation by tracking the target proton signal resulted in the characterization of 7-prenylisatin (1) with antimicrobial activity against Bacillus subtilis. The metabolite-guided genome mining of Streptomyces sp. MBT28 combined with proteomics identified a gene cluster with an indole prenyltransferase that catalyzes the conversion of tryptophan into 7-prenylisatin. This study underlines the applicability of NMR-based metabolomics in facilitating the discovery of novel antibiotics.
放线菌是抗菌剂、抗癌化合物和其他医学上重要产品的主要来源，其基因组具有广泛的生物合成潜力。筛选这些微生物的主要挑战在于激活隐秘生物合成基因簇的表达以及开发有效去除已知分子的技术。在此，我们报告了通过基于核磁共振代谢组学的策略并结合在生产菌株中引入链霉素抗性，鉴定出一种由链霉菌属MBT28产生的此前未鉴定的异吲哚酮类抗生素。通过追踪目标质子信号进行核磁共振引导的分离，得到了对枯草芽孢杆菌具有抗菌活性的7-异戊二烯基异吲哚酮（1）的表征。对链霉菌属MBT28进行代谢物引导的基因组挖掘并结合蛋白质组学，鉴定出一个含有吲哚异戊二烯基转移酶的基因簇，该酶催化色氨酸转化为7-异戊二烯基异吲哚酮。这项研究强调了基于核磁共振代谢组学在促进新型抗生素发现方面的适用性
