Streptococcus mutans is the major etiological agent of dental caries in humans. S. mutans overgrowth within dental biofilms can trigger biofilm dysbiosis, ultimately leading to the initiation or progression of dental caries. Polyketides and nonribosomal peptides (PKs/NRPs) are secondary metabolites with complex structures encoded by a cluster of biosynthetic genes. Although not essential for microbial growth, PKs/NRPs play important roles in physiological regulation. Three main classes of hybrid PKs/NRPs in S. mutans have been identified, including mutanobactin, mutanocyclin, and mutanofactin, encoded by the mub, muc, and muf gene clusters, respectively. These three hybrid PKs/NRPs play important roles in environmental adaptation, biofilm formation, and interspecies competition of S. mutans. In this review, we provide an overview of the major hybrid PKs/NRPs of S. mutans, including mutanobactin, mutanocyclin, and mutanofactin and address their ecological roles in dental biofilms. We place specific emphasis on important questions that are yet to be answered to provide novel insights into the cariogenic mechanism of S. mutans and facilitate improved management of dental caries. We highlight that S. mutans PKs/NRPs may be potential novel targets for the prevention and treatment of S. mutans-induced dental caries. The development of genomics, metabolomics, and mass spectrometry, together with the integration of various databases and bioinformatics tools, will allow the identification and synthesis of other secondary metabolites. Elucidating their physicochemical properties and their ecological roles in oral biofilms is crucial in the identification of novel targets for the ecological management of dental caries.

中文翻译：

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变形链球菌的聚酮化合物/非核糖体肽及其在牙齿生物膜中的生态作用

变形链球菌是人类龋齿的主要病原体。牙齿生物膜内变形链球菌过度生长会引发生物膜失调，最终导致龋齿的发生或进展。聚酮化合物和非核糖体肽（PK/NRP）是由一组生物合成基因编码的具有复杂结构的次级代谢产物。尽管 PK/NRP 对微生物生长不是必需的，但它在生理调节中发挥着重要作用。已鉴定出变形链球菌中三种主要类型的混合 PK/NRP ，包括分别由mub、muc和muf基因簇编码的 mutanobactin、mutanocyclin 和 mutanofactin。这三种混合PK/NRP在变形链球菌的环境适应、生物膜形成和种间竞争中发挥着重要作用。在这篇综述中，我们概述了变形链球菌的主要混合 PK/NRP ，包括变细菌素、变环素和变法丁，并阐述了它们在牙齿生物膜中的生态作用。我们特别强调尚未解答的重要问题，以便为变形链球菌的致龋机制提供新的见解，并促进改善龋齿的管理。我们强调，变形链球菌PKs/NRPs 可能是预防和治疗变形链球菌引起的龋齿的潜在新靶点。基因组学、代谢组学和质谱的发展，加上各种数据库和生物信息学工具的集成，将允许其他次级代谢物的鉴定和合成。阐明它们的理化特性及其在口腔生物膜中的生态作用对于确定龋齿生态管理的新靶点至关重要。