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

  • Natural Products - Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

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.

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(Figure adapted from Ref. [26])

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(Figure from Ref. [26])

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(Figure adapted from Ref. [37])

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Acknowledgements

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.

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Authors and Affiliations

  1. Naicons Srl, Viale Ortles 22/4, 20139, Milan, Italy

    Sonia I. Maffioli, Margherita Sosio & Stefano Donadio

  2. Waksman Institute of Microbiology and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ, 08854, USA

    Richard H. Ebright

Authors
  1. Sonia I. Maffioli
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  2. Margherita Sosio
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  3. Richard H. Ebright
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  4. Stefano Donadio
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Correspondence to Stefano Donadio.

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This article is part of the Special Issue “Natural Product Discovery and Development in the Genomic Era 2019”.

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Maffioli, S.I., Sosio, M., Ebright, R.H. et al. Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase. J Ind Microbiol Biotechnol 46, 335–343 (2019). https://doi.org/10.1007/s10295-018-2109-2

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  • DOI: https://doi.org/10.1007/s10295-018-2109-2

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