Streptococcus mutans is a common constituent of dental plaque and a major etiologic agent of dental caries (tooth decay). In this study, we elucidated the biosynthetic pathway encoded by muc, a hybrid polyketide synthase and nonribosomal peptide synthetase (PKS/NRPS) biosynthetic gene cluster (BGC), present in a number of globally distributed S. mutans strains. The natural products synthesized by muc included three N-acyl tetramic acid compounds (reutericyclin and two novel analogues) and an unacylated tetramic acid (mutanocyclin). Furthermore, the enzyme encoded by mucF was identified as a novel class of membrane-associated aminoacylases and was responsible for the deacylation of reutericyclin to mutanocyclin. A large number of hypothetical proteins across a broad diversity of bacteria were homologous to MucF, suggesting that this may represent a large family of unexplored acylases. Finally, S. mutans utilized the reutericyclin produced by muc to impair the growth of neighboring oral commensal bacteria. Since S. mutans must be able to out-compete these health-associated organisms to persist in the oral microbiota and cause disease, the competitive advantage conferred by muc suggests that this BGC is likely to be involved in S. mutans ecology and therefore dental plaque dysbiosis and the resulting caries pathogenesis.

中文翻译：

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致龋性变形链球菌可产生特异的四酸菌株抗生素，这些细菌会损害商业定居。

变形链球菌是牙菌斑的常见成分，也是龋齿（蛀牙）的主要病因。在这项研究中，我们阐明了muc，杂合聚酮化合物合酶和非核糖体肽合成酶（PKS / NRPS）生物合成基因簇（BGC）编码的生物合成途径，该基因簇存在于全球分布的变形链球菌菌株中。由muc合成的天然产物包括三种N-酰基四酸化合物（reutericyclin和两个新的类似物）和未酰化的四酸（mutanocyclin）。此外，由mucF编码的酶被鉴定为一类新的与膜相关的氨基酰基酶，并负责将reutericyclin脱酰基为mutanocyclin。跨多种细菌的大量假想蛋白质与MucF同源，提示这可能代表了一大批未开发的酰基转移酶。最后，变形链球菌利用由粘蛋白产生的reutericyclin损害邻近的口腔共生细菌的生长。由于变形链球菌必须能够与这些与健康相关的生物竞争，才能持久存在于口腔微生物群中并引起疾病，因此muc赋予的竞争优势表明该BGC可能与变形链球菌的生态有关，因此牙菌斑也可能参与其中。营养不良和由此引起的龋病发病机理。