{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T19:20:56Z","timestamp":1793215256071,"version":"4.5.0"},"reference-count":83,"publisher":"National Academy of Sciences","issue":"34","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000072","name":"HHS | NIH | National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["R01DE032732"],"award-info":[{"award-number":["R01DE032732"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"NSF | NSF Graduate Research Fellowship Program","doi-asserted-by":"publisher","award":["DGE2146752"],"award-info":[{"award-number":["DGE2146752"]}],"id":[{"id":"10.13039\/100023581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,8,26]]},"abstract":"<jats:p>\n                    Despite extensive efforts, our understanding of the virulence factors contributing to oral biofilm formation\u2014a hallmark of dental caries\u2014remains incomplete. We present evidence that the specialized metabolism of the oral microbiome is a critical yet underexplored factor in oral biofilm formation. Through microbiome analysis, we identified a hybrid nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) encoding biosynthetic gene cluster that correlates with dental caries and is widely represented in oral pathogens, including\n                    <jats:italic toggle=\"yes\">Streptococcus mutans<\/jats:italic>\n                    . This gene cluster produces two major mutanoclumpin metabolites, MC-584 and MC-586, which feature molecular scaffolds differing in a C\u2013C macrocyclic linkage. Both metabolites synergistically promote robust biofilm formation of\n                    <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                    through a rare dual-metabolite mode of action. Further, each metabolite binds uniquely to the\n                    <jats:italic toggle=\"yes\">S. mutans<\/jats:italic>\n                    cell surface, resulting in distinct multicellular morphologies. The biosynthesis of mutanoclumpins employs a unique chemical logic that produces two major products, rare within PKS-NRPS assembly lines. This study underscores the importance of characterizing genes implicated in human diseases through microbiome analysis and lays the foundation for exploring strategies to inhibit streptococci-induced dental caries.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2504492122","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T13:58:36Z","timestamp":1755611916000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":8,"title":["Synergistic action of specialized metabolites from divergent biosynthesis in the human oral microbiome"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8310-0635","authenticated-orcid":false,"given":"McKenna","family":"Loop Yao","sequence":"first","affiliation":[{"name":"Department of Chemical and Biomolecular Engineering, University of California 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Chemical and Biomolecular Engineering, University of California 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