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Isolation and structure elucidation of lipopeptide antibiotic taromycin B from the activated taromycin biosynthetic gene cluster.
The Journal of Antibiotics ( IF 2.1 ) Pub Date : 2018-Feb-01 , DOI: 10.1038/ja.2017.146
Kirk A Reynolds , Hanna Luhavaya , Jie Li , Samira Dahesh , Victor Nizet , Kazuya Yamanaka , Bradley S Moore

In the ongoing effort to unlock the chemical potential of marine bacteria, genetic engineering of biosynthetic gene clusters (BGCs) is increasingly used to awake or improve expression of biosynthetic genes that may lead to discovery of novel bioactive natural products. Previously, we reported the successful capture, engineering and heterologous expression of an orphan BGC from the marine actinomycete Saccharomonospora sp. CNQ-490, which resulted in the isolation of the novel lipopeptide antibiotic taromycin A. Herein we report the isolation and structure elucidation of taromycin B, the second most abundant product of the taromycin biosynthetic series, and show that taromycins A and B exhibit complex chromatographic properties indicative of interconverting conformations. Taromycins A and B display potent activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium clinical isolates, suggestive that the taromycin molecular scaffold is a promising starting point for further derivatization to produce compounds with promising antibiotic characteristics.

中文翻译:

从活化的塔霉素生物合成基因簇中分离脂肽抗生素塔霉素B。

在努力释放海洋细菌的化学潜能的过程中,越来越多地使用生物合成基因簇(BGC)的基因工程来唤醒或改善生物合成基因的表达,这可能会导致发现新的具有生物活性的天然产物。以前,我们报道了从海洋放线菌Saccharomonospora sp中成功捕获,工程化和异源表达了孤儿BGC。CNQ-490,其导致了新的脂肽抗生素taromycin A的分离。在此,我们报道了taromycin B(taromycin生物合成系列的第二大产物)的分离和结构解析,并表明taromycin A和B显示出复杂的色谱图指示相互转化构象的特性。
更新日期:2017-11-29
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