天然的脱肽类抗生素结合细菌核糖体的E位点

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https://www.nature.com/articles/s41586-026-10589-2

解决抗生素耐药性危机的一个关键挑战是识别新的抗菌化合物1.尽管过去80年中大多数抗生素的来源都是真菌和细菌产生的天然产物，尤其是放线菌，但由于已知药物支架的频繁被重新发现，这些抗生素已逐渐被淘汰2.目前的看法是，产抗生素的放线菌已被过度开采，几乎没有新颖性可发。我们展示了通过改进的分馏方法富集此前被忽视的次要产物，即使是研究充分的抗生素产放线菌菌株，也能提供具有独特作用机制的新化学支架。通过分馏土壤细菌中的天然产物库，我们展示了著名抗生素土四环素的来源链霉菌（Streptomyces rimosus）能产生一种环状脱肽类抗生素，我们称之为美尼科霉素。曼尼可霉素能杀死多重耐药肠杆菌科，且不易出现临床抗生素相关耐药性。生化、遗传和结构分析显示，曼尼科霉素结合于细菌核糖体大亚基的E位点，阻止tRNA的3′端进入E位点，并有效阻碍蛋白质合成的易位步骤，且具有序列特定情境。据我们所知，曼尼霉素是首个针对核糖体亚基中关键但尚未充分探索的E位点的抗菌剂，凸显了其作为新抗生素开发引领价值的价值。

GEN - Genetic Engineering and Biotechnology News (https://www.genengnews.com/topics/infectious-diseases/new-antibiotic-manikomycin-acts-on-novel-ribosomal-target/)

New Antibiotic, Manikomycin, Acts on Novel Ribosomal Target (https://www.genengnews.com/topics/infectious-diseases/new-antibiotic-manikomycin-acts-on-novel-ribosomal-target/)
Researchers discover manikomycin, a novel antibiotic that kills drug-resistant bacteria by targeting a previously unknown ribosomal target.
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Medical Xpress – 3 Jun 26 (https://medicalxpress.com/news/2026-06-antibiotic-drug-resistant-bacteria-previously.html)

New antibiotic kills drug-resistant bacteria by targeting previously unknown... (https://medicalxpress.com/news/2026-06-antibiotic-drug-resistant-bacteria-previously.html)
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