Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase
Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase
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DOI：
10.1007/s10295-018-2109-2
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发表时间：
2019-03-01
影响因子：
3.4
通讯作者：
Donadio, Stefano
中科院分区：
文献类型：
--
作者：
Maffioli, Sonia I.;Sosio, Margherita;Donadio, Stefano
假尿嘧啶霉素（PUM）是一种新型的含假尿嘧啶的肽基核苷类抗生素，通过与临床批准的利福霉素和非达霉素（fidaxomicin）类RNAP抑制剂不同的结合位点和机制抑制细菌RNA聚合酶（RNAP）。PUM是通过筛选RNAP抑制剂的微生物发酵提取物而发现的。在这篇综述中，我们描述了PUM的发现和表征。我们还描述了PUM的RNAP抑制和抗菌特性。最后，我们回顾了现有的PUM生物合成的基因簇和途径的信息，并通过搜索细菌基因组和宏基因组序列的PUM生物合成基因簇的pumJ，pseudouridine合酶基因类似的序列，发现额外的新的含pseudouridine核苷抗生素的潜力。
Pseudouridimycin (PUM) is a novel pseudouridine-containing peptidyl-nucleoside antibiotic that inhibits bacterial RNA polymerase (RNAP) through a binding site and mechanism different from those of clinically approved RNAP inhibitors of the rifamycin and lipiarmycin (fidaxomicin) classes. PUM was discovered by screening microbial fermentation extracts for RNAP inhibitors. In this review, we describe the discovery and characterization of PUM. We also describe the RNAP-inhibitory and antibacterial properties of PUM. Finally, we review available information on the gene cluster and pathway for PUM biosynthesis and on the potential for discovering additional novel pseudouridine-containing nucleoside antibiotics by searching bacterial genome and metagenome sequences for sequences similar to pumJ, the pseudouridine-synthase gene of the PUM biosynthesis gene cluster.