title: Fungal biofilm inhibitors from a human oral microbiome-derived bacterium.
abstract: The human mouth is home to a rich assortment of native and transient microorganisms. One of the commonly encountered bacterial species, Streptococcus mutans, was shown to generate the novel hybrid polyketide-nonribosomal peptide metabolite mutanobactin A (1). We have characterized three new analogues, mutanobactins B-D (2-4), and subjected these compounds to further biomedical evaluation. Metabolites 1, 2, and 4 were found to inhibit biofilm formation by the fungal oral-pathogen Candida albicans. Compound 4 was the most potent metabolite with an IC(50) value of 5.3 ± 0.9 μM. Using a combination of Marfey's analysis, proton spin-spin coupling, and (1)H-(1)H NOESY data, we proposed absolute configuration assignments in toto for 1-3 and a partial assignment for 4. In addition, feeding studies with isotopically labeled precursor metabolites (acetate and amino acids) have helped to determine the biosynthetic origins of this unique natural product family.
authors.affiliation: Natural Products Discovery Group, Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK 73019, USA.
authors.forename: Xiaoru
authors.initials: X
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.forename: Jianlan
authors.initials: J
authors.lastname: You
authors.forename: Jarrod B
authors.initials: JB
authors.lastname: King
authors.forename: Robert H
authors.initials: RH
authors.lastname: Cichewicz
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy; D005285:Fermentation; D006801:Humans; D054892:Metagenome; D008958:Models, Molecular; D009055:Mouth / Q000382:microbiology*; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000494:pharmacology; D013295:Streptococcus mutans / Q000378:metabolism*
chemical_list: D000935:Antifungal Agents; D010456:Peptides, Cyclic