{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:57:29Z","timestamp":1789891049495,"version":"4.0.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"3-4","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM041376"],"award-info":[{"award-number":["GM041376"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI104660"],"award-info":[{"award-number":["AI104660"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["30190679"],"award-info":[{"award-number":["30190679"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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.<\/jats:p>","DOI":"10.1007\/s10295-018-2109-2","type":"journal-article","created":{"date-parts":[[2018,11,21]],"date-time":"2018-11-21T03:16:05Z","timestamp":1542770165000},"page":"335-343","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Discovery, properties, and biosynthesis of pseudouridimycin, an antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase"],"prefix":"10.1093","volume":"46","author":[{"given":"Sonia I","family":"Maffioli","sequence":"first","affiliation":[{"name":"Naicons Srl Viale Ortles 22\/4 20139 Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Sosio","sequence":"additional","affiliation":[{"name":"Naicons Srl Viale Ortles 22\/4 20139 Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H","family":"Ebright","sequence":"additional","affiliation":[{"name":"0000 0004 1936 8796 grid.430387.b Waksman Institute of Microbiology and Department of Chemistry and Chemical Biology Rutgers University 08854 Piscataway NJ USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Donadio","sequence":"additional","affiliation":[{"name":"Naicons Srl Viale Ortles 22\/4 20139 Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"2023072013285961800_CR1","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3389\/fphar.2015.00237","article-title":"Natural products and drug discovery: a survey of stakeholders in industry and academia","volume":"6","author":"Amirkia","year":"2015","journal-title":"Front Pharmacol"},{"key":"2023072013285961800_CR2","doi-asserted-by":"publisher","first-page":"E4178","DOI":"10.1073\/pnas.1502368112","article-title":"CBR antimicrobials inhibit RNA polymerase via at least two bridge-helix cap-mediated effects on nucleotide addition","volume":"112","author":"Bae","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072013285961800_CR3","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/nature07510","article-title":"Transcription inactivation through local refolding of the RNA polymerase structure","volume":"45","author":"Belogurov","year":"2009","journal-title":"Nature"},{"key":"2023072013285961800_CR4","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1038\/nature17042","article-title":"Antibacterial drug discovery in the resistance era","volume":"529","author":"Brown","year":"2016","journal-title":"Nature"},{"key":"2023072013285961800_CR5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1038\/ja.2016.72","article-title":"Antibiotics in the clinical pipeline at the end of 2015","volume":"70","author":"Butler","year":"2017","journal-title":"J Antibiot"},{"key":"2023072013285961800_CR6","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1016\/S0092-8674(01)00286-0","article-title":"Structural mechanism for rifampicin inhibition of bacterial RNA polymerase","volume":"104","author":"Campbell","year":"2001","journal-title":"Cell"},{"key":"2023072013285961800_CR7","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s11101-014-9367-z","article-title":"The pharmaceutical industry and natural products: historical status and new trends","volume":"14","author":"David","year":"2015","journal-title":"Phytochem Rev"},{"key":"2023072013285961800_CR8","doi-asserted-by":"publisher","first-page":"e02451","DOI":"10.7554\/eLife.02451","article-title":"Transcription inhibition by the depsipeptide antibiotic salinamide A","volume":"3","author":"Degen","year":"2014","journal-title":"eLife"},{"key":"2023072013285961800_CR9","doi-asserted-by":"publisher","first-page":"1857","DOI":"10.4155\/fmc-2017-0188","article-title":"Novel RNA polymerase inhibitor found in soil extracts provides hope for future antibacterial drugs","volume":"9","author":"Ebright","year":"2017","journal-title":"Future Med Chem"},{"key":"2023072013285961800_CR10","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1107\/S0907444904003506","article-title":"Expression, purification, crystallization and preliminary diffraction studies of the tRNA pseudouridine synthase TruD from Escherichia coli","volume":"60","author":"Ericsson","year":"2004","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"2023072013285961800_CR11","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1016\/j.str.2015.06.009","article-title":"Structural basis of transcription inhibition by CBR hydroxamidines and CBR pyrazoles","volume":"23","author":"Feng","year":"2015","journal-title":"Structure"},{"key":"2023072013285961800_CR12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.coph.2015.06.003","article-title":"The global challenge of new classes of antibacterial agents: an industry perspective","volume":"24","author":"Fernandes","year":"2015","journal-title":"Curr Opin Pharmacol"},{"key":"2023072013285961800_CR13","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/S1568-7864(03)00024-7","article-title":"Use of the rpoB gene to determine the specificity of base substitution mutations on the Escherichia coli chromosome","volume":"2","author":"Garibyan","year":"2003","journal-title":"DNA Repair"},{"key":"2023072013285961800_CR14","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1039\/C7NP00026J","article-title":"Actinomycetes: still a source of novel antibiotics","volume":"34","author":"Genilloud","year":"2017","journal-title":"Nat Prod Rep"},{"key":"2023072013285961800_CR15","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.chembiol.2006.09.009","article-title":"Pseudouridine synthases","volume":"13","author":"Hamma","year":"2006","journal-title":"Chem Biol"},{"key":"2023072013285961800_CR16","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.sbi.2009.10.010","article-title":"Structures of RNA polymerase\u2013antibiotic complexes","volume":"19","author":"Ho","year":"2009","journal-title":"Curr Opin Struct Biol"},{"key":"2023072013285961800_CR17","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/S0167-7012(03)00190-8","article-title":"A kinetic microplate method for quantifying the antibacterial properties of biological fluids","volume":"55","author":"Holowachuk","year":"2003","journal-title":"J Microbiol Methods"},{"key":"2023072013285961800_CR18","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1021\/cb400692w","article-title":"A glycosylated, labionin-containing lanthipeptide with marked antinociceptive activity","volume":"9","author":"Iorio","year":"2014","journal-title":"ACS Chem Biol"},{"key":"2023072013285961800_CR19","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/0022-2836(88)90517-7","article-title":"Mapping and sequencing of mutations in the Escherichia coli rpoB gene that lead to rifampicin resistance","volume":"202","author":"Jin","year":"1988","journal-title":"J Mol Biol"},{"key":"2023072013285961800_CR20","doi-asserted-by":"publisher","first-page":"14469","DOI":"10.1074\/jbc.M110.212902","article-title":"An activity map of the Escherichia coli RNA polymerase bridge helix","volume":"286","author":"Jovanovic","year":"2011","journal-title":"J Biol Chem"},{"key":"2023072013285961800_CR21","doi-asserted-by":"publisher","first-page":"3273","DOI":"10.1038\/s41467-018-05781-6","article-title":"Discovery of cationic nonribosomal peptides as Gram-negative antibiotics through global genome mining","volume":"9","author":"Li","year":"2018","journal-title":"Nat Comm"},{"key":"2023072013285961800_CR22","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.molcel.2017.03.001","article-title":"Structural basis of Mycobacterium tuberculosis transcription and transcription inhibition","volume":"66","author":"Lin","year":"2017","journal-title":"Mol Cell"},{"key":"2023072013285961800_CR23","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.molcel.2018.02.026","article-title":"Structural basis of transcription inhibition by fidaxomicin (lipiarmycin A3)","volume":"70","author":"Lin","year":"2018","journal-title":"Mol Cell"},{"key":"2023072013285961800_CR24","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1128\/MMBR.00055-15","article-title":"Bacterial transcription as a target for antibacterial drug development","volume":"80","author":"Ma","year":"2016","journal-title":"Microbiol Mol Biol Rev"},{"key":"2023072013285961800_CR25","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1007\/s10295-015-1703-9","article-title":"Advancing cell wall inhibitors towards clinical applications","volume":"43","author":"Maffioli","year":"2016","journal-title":"J Ind Microbiol Biotechnol"},{"key":"2023072013285961800_CR26","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1016\/j.cell.2017.05.042","article-title":"Antibacterial nucleoside-analog inhibitor of bacterial RNA polymerase","volume":"169","author":"Maffioli","year":"2017","journal-title":"Cell"},{"key":"2023072013285961800_CR27","doi-asserted-by":"publisher","first-page":"E17","DOI":"10.3390\/antibiotics5020017","article-title":"The oligopeptide permease Opp mediates illicit transport of the bacterial P-site decoding inhibitor GE81112","volume":"5","author":"Maio","year":"2016","journal-title":"Antibiotics"},{"key":"2023072013285961800_CR28","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1111\/1751-7915.12123","article-title":"Discovering new bioactive compounds from microbial sources","volume":"7","author":"Monciardini","year":"2014","journal-title":"Microb Biotechnol"},{"key":"2023072013285961800_CR29","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1016\/j.cell.2008.09.033","article-title":"The RNA polymerase \u201cswitch region\u201d is a target for inhibitors","volume":"135","author":"Mukhopadhyay","year":"2008","journal-title":"Cell"},{"key":"2023072013285961800_CR30","volume-title":"Performance standards for Antimicrobial Susceptibility Testing; Twentieth Informational Supplement\u2014CLSI document M100-S20 (2010) NCCLS","year":"2010"},{"key":"2023072013285961800_CR31","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1021\/acs.jnatprod.5b01055","article-title":"Natural products as sources of new drugs from 1981 to 2014","volume":"79","author":"Newman","year":"2016","journal-title":"J Nat Prod"},{"key":"2023072013285961800_CR32","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.tim.2014.10.007","article-title":"Nucleoside antibiotics: biosynthesis, regulation, and biotechnology","volume":"23","author":"Niu","year":"2015","journal-title":"Trends Microbiol"},{"key":"2023072013285961800_CR33","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1038\/ja.2014.16","article-title":"Isolation and structure elucidation of the nucleoside antibiotic strepturidin from Streptomyces albus DSM 40763","volume":"67","author":"Pesic","year":"2014","journal-title":"J Antibiot"},{"key":"2023072013285961800_CR34","doi-asserted-by":"publisher","first-page":"5601","DOI":"10.1073\/pnas.1614680114","article-title":"Retrospective analysis of natural products provides insights for future discovery trends","volume":"114","author":"Pye","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"2023072013285961800_CR35","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0021-9258(18)53981-8","article-title":"Dominant lethal mutations near the 5\u2032 substrate binding site affect RNA polymerase propagation","volume":"268","author":"Sagitov","year":"1993","journal-title":"J Biol Chem"},{"key":"2023072013285961800_CR36","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.2217\/fmb.15.67","article-title":"Natural products as a source of drug leads to overcome drug resistance","volume":"10","author":"Silver","year":"2016","journal-title":"Future Microbiol"},{"key":"2023072013285961800_CR37","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.chembiol.2018.02.008","article-title":"Analysis of the pseudouridimycin biosynthetic pathway provides insights into the formation of C-nucleoside antibiotics","volume":"25","author":"Sosio","year":"2018","journal-title":"Cell Chem Biol"},{"key":"2023072013285961800_CR38","doi-asserted-by":"publisher","first-page":"4202","DOI":"10.1093\/nar\/gki688","article-title":"The involvement of the aspartate triad of the active center in all catalytic activities of multisubunit RNA polymerase","volume":"33","author":"Sosunov","year":"2005","journal-title":"Nucl Acids Res"},{"key":"2023072013285961800_CR39","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.mib.2011.07.030","article-title":"New target for inhibition of bacterial RNA polymerase: \u201cswitch region\u201d","volume":"14","author":"Srivastava","year":"2011","journal-title":"Curr Opin Microbiol"},{"key":"2023072013285961800_CR40","doi-asserted-by":"publisher","first-page":"38087","DOI":"10.1074\/jbc.C400316200","article-title":"Discrimination against deoxyribonucleotide substrates by bacterial RNA polymerase","volume":"279","author":"Svetlov","year":"2004","journal-title":"J Biol Chem"},{"key":"2023072013285961800_CR41","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.molcel.2005.07.020","article-title":"Structural basis of transcription inhibition by antibiotic streptolydigin","volume":"19","author":"Temiakov","year":"2005","journal-title":"Mol Cell"},{"key":"2023072013285961800_CR42","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.cell.2005.07.017","article-title":"Inhibition of bacterial RNA polymerase by streptolydigin: stabilization of a straight-bridge-helix active-center conformation","volume":"122","author":"Tuske","year":"2005","journal-title":"Cell"},{"key":"2023072013285961800_CR43","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1039\/B816215H","article-title":"Antimicrobial antibiotics targeting cell wall assembly: recent advances in structure-function studies and nucleoside biosynthesis","volume":"27","author":"Winn","year":"2010","journal-title":"Nat Prod Rep"},{"key":"2023072013285961800_CR44","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1039\/C7NP00019G","article-title":"Opportunities for natural products in 21st century antibiotic discovery","volume":"34","author":"Wright","year":"2017","journal-title":"Nat Prod Rep"},{"key":"2023072013285961800_CR45","doi-asserted-by":"publisher","first-page":"115","DOI":"10.4161\/trns.19887","article-title":"Multiple active centers of multi-subunit RNA polymerases","volume":"3","author":"Yuzenkova","year":"2012","journal-title":"Transcription"},{"key":"2023072013285961800_CR46","first-page":"e02450","volume":"3","author":"Zhang","year":"2014","journal-title":"GE23077 binds to the RNA polymerase \u2018i\u2019 and \u2018i\u2009+\u20091\u2019 sites and prevents the binding of initiating nucleotides. eLife"}],"container-title":["Journal of Industrial Microbiology and Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10295-018-2109-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10295-018-2109-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jimb\/article-pdf\/46\/3-4\/335\/50915866\/jimb0335.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10295-018-2109-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/academic.oup.com\/jimb\/article-pdf\/46\/3-4\/335\/50915866\/jimb0335.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,20]],"date-time":"2023-07-20T12:20:05Z","timestamp":1689855605000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimb\/article\/46\/3-4\/335\/5997225"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,1]]},"references-count":46,"journal-issue":{"issue":"3-4","published-online":{"date-parts":[[2019,3,1]]},"published-print":{"date-parts":[[2019,3,1]]}},"URL":"https:\/\/doi.org\/10.1007\/s10295-018-2109-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/106906","asserted-by":"object"}]},"ISSN":["1476-5535","1367-5435"],"issn-type":[{"value":"1476-5535","type":"electronic"},{"value":"1367-5435","type":"print"}],"subject":[],"published-other":{"date-parts":[[2019,3,1]]},"published":{"date-parts":[[2019,3,1]]},"assertion":[{"value":"21 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 November 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}