Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase. (1st March 2019)

• Record Type: Journal Article
• Authors: Maffioli, Sonia I; Sosio, Margherita; Ebright, Richard H; Donadio, Stefano
• Is Part Of: Journal of industrial microbiology & biotechnology. Volume 46:Number 3/4(2019)
• Page Start: 335
• Page End: 343
• Publication Date: 2019-03-01
• Subjects: Bacterial RNAP -- Nucleoside Analog Inhibitors -- Fidaxomicin -- Pseudouridine Synthase -- Microbial Natural Products; Industrial microbiology -- Periodicals; 660.62
• DOI: 10.1007/s10295-018-2109-2
• Languages: English
• ISSNs: 1367-5435

Abstract

Abstract: 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.