本项目拟针对丙酸蛛网菌（Arachnia propionica/Pseudopropionibacterium propionicum）这一人体口腔共生菌的次级代谢进行系统的研究。细菌的次级代谢物在其对外防御、种群调控、获取养分、物种交互等多个方面都具有重要功能。丙酸蛛网菌是人体口腔中广泛存在的一种厌氧细菌，但目前针对该共生菌的次级代谢没有系统的研究。本项目拟采用和成像质谱结合的高通量小分子激活剂筛选技术，实现对丙酸蛛网菌次级代谢生物合成基因簇的激活，分离表征被激活的次级代谢物并研究其生物功能。在此基础上，项目将针对丙酸蛛网菌和变异链球菌这一对口腔共生菌和病原菌构成的交互体系，探索细菌次级代谢物在口腔微生物组中具有的生态学功能，为研究口腔共生菌及其次级代谢在口腔疾病和健康中的作用提供基础。

Pseudopropionibacterium propionicum is a widely spread anaerobic commensal bacterium found in human oral microbiota. It accounts for a substantial amount of the oral microbiome, however so far there are no systematic reports about the secondary metabolism of P. propionicum. Bacterial secondary metabolites play important roles in bacterial survival, as they act as the defense warfare, quorum sensing signals, metal transporters, interspecies communication signals, etc. We have found that P. propionicum has at least three biosynthetic gene clusters corresponding to ribosomally synthesized and post-translational modified peptide, polyketide, and non-ribosomally synthesized peptide products. In this study, the secondary metabolite gene clusters of P. propionicum will be activated by imaging mass spectrometry assisted high-throughput elicitor screening. The activated secondary metabolites will be isolated, purified, and structurally elucidated. To understand the physiological and ecological functions of such secondary metabolites, the effects and regulation of the molecules will be investigated in the co-culture of P. propionicum and Streptococcus mutans. This interspecies interaction setting between oral commensal bacterium and pathogenic bacterium will help better understand how secondary metabolites from commensal bacteria help maintain the composition of human oral microbiota. The results may also lead to the discovery of new secondary metabolites from oral microbiome that can combat microbial pathogens.