biostudies-literatureRush JSDOE | SC | Chemical Sciences, Geosciences, and Biosciences Division (Chemical Sciences, Geosciences, and Energy Biosciences)The Knut and Alice Wallenberg FoundationBLRD VANIDCR NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial ResearchVetenskapsrådetU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIAID NIH HHSDOE | SC | Chemical Sciences, Geosciences, and Biosciences DivisionU.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious DiseasesVetenskapsrådet (Swedish Research Council)NIGMS NIH HHS954https://www.ebi.ac.uk/biostudies/studies/S-EPMC11754754biostudies-literatureUnknown16(1)Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and SccQ glycosyltransferases, and α-Glc attached to position 4 of 2-rhamnose installed by SccN working in tandem with an unknown enzyme. Both the major and the minor β-Glc modifications control bacterial morphology, but only the GroP and major Glc modifications are critical for biofilm formation.Nature communicationsStructure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide.PMC11754754R01 DE0289162022-03014DE-SC0015662R01 AI143690R24 GM137782I01 BX005637IK6 BX006469Korotkova NKenner CWBlack IDeng PAzadi PHeiss CWidmalm GRush JSZamakhaeva SKorotkov KVMurner NRMorris AJfalseStructure and mechanism of biosynthesis of Streptococcus mutans cell wall polysaccharide.Streptococcus mutans, the causative agent of human dental caries, expresses a cell wall attached Serotype c-specific Carbohydrate (SCC) that is critical for cell viability. SCC consists of a polyrhamnose backbone of →3)α-Rha(1 → 2)α-Rha(1→ repeats with glucose (Glc) side-chains and glycerol phosphate (GroP) decorations. This study reveals that SCC has one predominant and two more minor Glc modifications. The predominant Glc modification, α-Glc, attached to position 2 of 3-rhamnose, is installed by SccN and SccM glycosyltransferases and is the site of the GroP addition. The minor Glc modifications are β-Glc linked to position 4 of 3-rhamnose installed by SccP and SccQ glycosyltransferases, and α-Glc attached to position 4 of 2-rhamnose installed by SccN working in tandem with an unknown enzyme. Both the major and the minor β-Glc modifications control bacterial morphology, but only the GroP and major Glc modifications are critical for biofilm formation.2025-01-01T00:00:00Z2025 Jan2026-06-01T18:05:45.607Z2025-04-04T22:07:05.52ZS-EPMC117547543984348710.1038/s41467-025-56205-1