Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase
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.
This work was partially supported by NIH Grants GM041376 and AI104660 to RHE and partially supported from a Grant from MIUR Regione Lombardia to NAICONS. We are grateful to all coauthors of the two papers that provided the material for this review.
- 30.National Committee for Clinical Laboratory Standards (2010) Performance standards for Antimicrobial Susceptibility Testing; Twentieth Informational Supplement—CLSI document M100-S20 (2010) NCCLS. Wayne, PennsylvaniaGoogle Scholar