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一种含硫的核酸抗生素来自Photorhabdus

Sangkeun Son¹, Negar Shahsavari¹, Thomas Privalsky¹

¹Department of Biology, Antimicrobial Discovery Center, Northeastern University, Boston, Massachusetts, USA.

|October 31, 2025

概括

我们发现了4'-thiothymidine (4'sT),一种来自Photorhabdus asymbiotica的新型核酸抗生素. 它对大肠杆菌等细菌的活性取决于蒂米丁的新陈代谢,突出了抗生素选择性的代谢背景.

科学领域:

微生物学微生物学
生物化学生物化学
药物发现药物发现药物发现

背景情况:

新型抗生素的发现对于对抗日益增长的抗菌素耐药性至关重要.
沉默的生物合成基因集群是新抗菌化合物的有希望的来源.
核类比物可以通过干扰DNA复制来作为抗生素.

研究的目的:

报告发现和描述4 -thiothymidine (4'sT),一种新型核酸抗生素.
阐明4'sT的生物合成途径和作用机制.
研究4'sT.对抗菌株选择性活动的因素.

主要方法:

从*Photorhabdus asymbiotica*中分离和描述4'sT.
4'sT生物合成基因集群的识别和异质表达.
抗微生物敏感性测试和涉及DNA结合和SOS响应的机制研究.
对耐药和易感细菌菌株中蒂米丁救援通路活性的分析.

主要成果:

发现了一种含硫的核酸抗生素4'sT,并阐明了它的结构.
生物合成基因集群,包括一个激进的SAM酶,被确定,证实了它的起源.
4'sT是一种由胺基酶激活的前药物,被纳入DNA,抑制复制.
对大肠杆菌的抗菌株选择性活性与蒂米丁代谢的差异有关,而不是目标变化.

结论:

4'sT是一种新型核酸抗生素,具有独特的4'-thiosugar部分.
代谢背景,特别是提米丁代谢,决定了4'sT的选择性活性.
里芬素耐药性查是发现静默生物合成基因集群和发现新抗生素的可行策略.

关键词:

埃舍里希亚大肠杆菌 (Escherichia coli) 是一个大肠杆菌.摄影工作室的摄影师.天然抗微生物产品天然抗微生物产品.核酸类型的类似物提米丁酶酶的使用方法

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