{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:01:21Z","timestamp":1785416481938,"version":"3.56.0"},"reference-count":56,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2018-05949"],"award-info":[{"award-number":["RGPIN-2018-05949"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2025,9,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      \u03b2-Lactam antibiotics and \u03b2-lactamase inhibitor combinations are essential for combating antimicrobial resistance, with many \u03b2-lactams, including clavulanic acid (CA), themselves being products of specialized metabolic pathways in bacteria. CA is a potent \u03b2-lactamase inhibitor, and in known producers such as\n                      <jats:italic toggle=\"yes\">Streptomyces clavuligerus<\/jats:italic>\n                      , it is co-produced with the \u03b2-lactam antibiotic cephamycin C, and their biosynthetic gene clusters (BGCs) are always located adjacent on the chromosome. However, CA-like BGCs have also been identified in other bacteria, often without an accompanying cephamycin C BGC. Similarly, carbapenem BGCs (a subclass of \u03b2-lactams), such as those responsible for producing MM 4550, a member of the olivanic acid complex with both antibiotic and \u03b2-lactamase inhibitory properties, are also found in\n                      <jats:italic toggle=\"yes\">Streptomyces<\/jats:italic>\n                      species. This study investigated antimicrobial and \u03b2-lactamase inhibitory activity production in\n                      <jats:italic toggle=\"yes\">Streptomyces pratensis<\/jats:italic>\n                      and 10 environmental\n                      <jats:italic toggle=\"yes\">Streptomyces<\/jats:italic>\n                      isolates (JAC strains) containing CA-like and MM 4550-like BGCs but lacking cephamycin C BGCs. While the examined isolates do not produce CA, they synthesize predicted monocyclic \u03b2-lactam precursors of CA, which potentially represent a previously unrecognized, primordial form of \u03b2-lactamase inhibitor. Several JAC isolates also exhibited both \u03b2-lactamase inhibitory and \u03b2-lactam antibiotic activities, indicating that the carbapenem BGC is active in these strains. Gene disruption analysis confirmed that MM 4550-like carbapenem BGCs contribute to both antimicrobial and \u03b2-lactamase inhibitory activities, whereas CA-like clavam BGCs only contribute to \u03b2-lactamase inhibition. The findings also suggest that both \u03b2-lactam BGC types co-occur in nature more frequently than previously recognized, possibly with functional significance and potential applications in the discovery of novel antibiotic-inhibitor combinations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The global rise of antimicrobial resistance calls for innovative strategies to preserve the efficacy of existing antibiotics and identify new therapeutic agents. This study explores naturally occurring \u03b2-lactamase inhibitors and antibiotics beyond well-characterized systems. Investigation of clavulanic acid (CA)-like and MM 4550-like biosynthetic gene clusters (BGCs) in\n                      <jats:italic toggle=\"yes\">Streptomyces pratensis<\/jats:italic>\n                      and related environmental isolates revealed a broader occurrence of monocyclic \u03b2-lactam precursors and dual-function carbapenems in nature. These findings offer new insights into \u03b2-lactam co-production and further indicate that unlinked \u03b2-lactam BGCs may have functional significance. The study also highlights the importance of exploring silent counterparts of known BGCs as potential sources of bioactive metabolites, enhancing our understanding of \u03b2-lactam BGC diversity and evolution. Notably, it identifies \u03b2-lactamase inhibitor and antibiotic-producing strains, opening new avenues for discovering antibiotic-inhibitor combinations of relevance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00188-25","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T12:00:38Z","timestamp":1756123238000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Functional insights into\n                    <i>Streptomyces<\/i>\n                    isolates containing both clavulanic acid-like and carbapenem biosynthetic gene clusters"],"prefix":"10.1128","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2436-682X","authenticated-orcid":true,"given":"Kapil","family":"Tahlan","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04haebc03","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of 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