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Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase

Author:
Maffioli, Sonia I., Sosio, Margherita, Ebright, Richard H., Donadio, Stefano
Source:
Journal of industrial microbiology & biotechnology 2019 v.46 no.3-4 pp. 335-343
ISSN:
1367-5435
Subject:
DNA-directed RNA polymerase, antibacterial properties, binding sites, biosynthesis, fermentation, metagenomics, multigene family, nucleosides, screening
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.
Agid:
6324778