国际口腔医学杂志

国际口腔医学杂志 ›› 2026, Vol. 53 ›› Issue (1): 98-106.doi: 10.7518/gjkq.2026204

• 综述 • 上一篇    下一篇

变异链球菌次级代谢产物Mutanobactin的研究进展

夏江澜(),程兴群,吴红崑()   

  1. 口腔疾病防治全国重点实验室 国家口腔医学中心 口腔疾病国家临床医学研究中心四川大学华西口腔医院老年口腔科 成都 610041
  • 收稿日期:2024-12-04 修回日期:2025-04-21 出版日期:2026-01-01 发布日期:2025-12-31
  • 通讯作者: 吴红崑
  • 作者简介:夏江澜，硕士，Email：1421934487@qq.com
  • 基金资助:
    国家自然科学基金青年项目(82101002);四川省重点研发计划(2021YFSY0011)

Research progress on the secondary metabolite Mutanobactin of Streptococcus mutans

Jianglan Xia(),Xingqun Cheng,Hongkun Wu()   

  1. State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Dept. of Geriatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2024-12-04 Revised:2025-04-21 Online:2026-01-01 Published:2025-12-31
  • Contact: Hongkun Wu
  • Supported by:
    National Natural Science Foundation of China(82101002);Key Research and Development Program of Sichuan Province(2021YFSY0011)

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摘要：

龋病是在以细菌为主的多因素作用下，发生于牙体硬组织的慢性感染性疾病，变异链球菌被认为是人类龋病的主要病原体。Mutanobactin，变异链球菌的次级代谢产物，是一种非核糖体肽/聚酮杂交产物，由位于TnSmu2基因岛中的mub基因合成，主要有Mutanobactin A、B、C、D 4种类型，能够体外合成。变异链球菌Mutanobactin在抵抗细菌氧化应激、生态竞争及免疫调节等中发挥作用，产量受细菌内多种调控机制、外界环境及共生菌的影响。本文主要针对Mutanobactin的合成、生理学作用及相关调控机制等方面进行综述，旨在为变异链球菌致龋毒力的机制探索提供新思路，为口腔微生态调节及龋病防治提供新途径。

关键词: 变异链球菌, 次级代谢产物, Mutanobactin, 龋病, 微生态平衡

Abstract:

Dental caries is a chronic infectious disease occurring in the hard tissue of teeth under the influence of bacteria. Streptococcus mutans (S. mutans) is considered the major etiological agent of dental caries in humans. Mutanobactin is one of the secondary metabolites of S. mutans. It is one of non-ribosomal peptide/polyketide hybrid products and is mainly synthesized by the mub gene located in the TnSmu2 gene island. Additionally, the major types of this product are Mutanobactin A, B, C, and D, which can be synthesized in vitro. The Mutanobactin of S. mutans plays an important role in physiological functions ranging from oxidative stress resistance and interspecies competition to immunoregulation. Moreover, its production is affected by various regulatory mechanisms in vivo, the external environment, and commensal bacteria. This work mainly reviews the synthesis, physiological role, and related regulatory mechanisms of Mutanobactin to provide a new horizon for elucidating the caries virulence of S. mutans and new methods for oral microecological regulation and management of caries.

Key words: Streptococcus mutans, secondary metabolite, Mutanobactin, dental caries, microecological balance

中图分类号: 

  • R78

图1

变异链球菌UA159 mub基因系统进化发育树分析"

图2

mub基因转录方向示意图"

表 1

变异链球菌UA159体内NRPS/PKS基因"

基因推定的功能
SMU.1334C（sfp）磷酸泛酰巯基乙胺基转移酶
SMU.1335C（fabK）烯酰（酰基载体蛋白）还原酶
SMU.1336C（pksD）丙二酰辅酶A转酰酶
SMU.1337Cα/β-水解酶
SMU.1338C（mefE）ABC转运蛋白，大环内酯通透酶
SMU.1339C（bacC<bacD>）杆菌肽合成酶
SMU.1340C（bacA 2）表面活性素合成酶（杆菌肽合成酶1）
SMU.1341C（grs）短杆菌肽S合成酶2（短杆菌肽S合成酶）
SMU.1342C（bac A）杆菌肽合成酶1
SMU.1343C（pksC）杂合非核糖体肽合成酶/聚酮合成酶（聚酮合成酶）
SMU.1344C（fabD）酰基载体蛋白S-丙二酰转移酶
SMU.1345C（ituA）类似枯草芽孢杆菌中MycA的酰基辅酶A合成酶/连接酶
SMU.1346C（bacT）Ⅱ型硫酯酶
SMU.1347C（ymbB<ylbB>）ABC转运蛋白通透酶
SMU.1348C（pasA<psaA>）ATP依赖性ABC转运蛋白
SMU.1349TetR家族转录调节因子

图3

Mutanobactin A合成示意图结构域简写：A，腺苷酸化；C，缩合；E，差向异构化；KS，酮合酶；R，还原；T，硫醇化。"

表 2

Mutanobactin生物合成调控"

调节因子推定的主要作用
FtsH降解堆积的Mutanobactin
VicR解除HLP对基因表达的抑制，促进基因表达
VicK促进合成基因表达（SMU.1334、SMU.1335、SMU.1336、SMU.1341、SMU.1342、SMU.1344）
SMU.833蛋白促进合成相关蛋白表达（SMU.1342、SMU.1340、SMU.1341）
TreR促进合成相关蛋白表达（SMU.1342、SMU.1344c、SMU.1340、SMU.1341s、SMU.1345c、SMU.1339、SMU.1336）
XIP促进合成相关基因表达（SMU.1335c-1340）
c-di-AMP促进合成相关基因表达（SMU.1334、SMU.1335c、SMU.1336、SMU.1337c）
ClpPΔclpP突变株表现出mubR表达上调，SMU.1339-SMU.1348显著下调

图4

Mutanobactin A、B、C、D的化学结构"

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