School of Food and Health, Beijing Technology and Business University, Beijing, 100048, China.
Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University, Beijing, 100048, China.
World J Microbiol Biotechnol. 2024 Oct 26;40(11):366. doi: 10.1007/s11274-024-04172-y.
Bacteriocin is a kind of natural substance that can effectively inhibit bacteria, but its production usually limited by environment. Co-culture is a strategy to stimulate bacteriocin production. Bifidocin A produced by Bifidobacterium animalis BB04, is a novel bacteriocin with a broad-spectrum antimicrobial active of foodborne bacteria. In order to enhance bifidocin A production, bacteriocin-inducing strains were screened firstly in co-cultivation. Then, the molecular mechanism of co-cultural induction was investigated by transcriptomic and proteomic analysis. Finally, the key inducing metabolites were identified by using targeted metabolomic technology. The results showed that Wickerhamomyces anomalus Y-5 in co-cultivation could significantly enhance bifidocin A production, with a 3.00-fold increase compared to mono-culture. The induction may not depend on direct contact with cells and may instead be attributed to be continuous exposure to inducing substances at specific concentration. In co-cultivation, W. anomalus Y-5 up-regulated Hxk2 and Tap42 to activate Glucose-cAMP and Tor and HOG-MAPK pathway, stimulated the expression of the retrograde gene, produced glutamine and glycerol to maintain activity. During this process, glutamine, inosine, guanosine, adenine, uracil, fumaric acid and pyruvic acid produced by W. anomalus Y-5 could induce the synthesis of bifidocin A. In conclusion, W. anomalus Y-5 in co-cultivation induced the synthesis of bifidocin A by regulating various signaling pathways to produce inducing substances. These findings establish a foundation for high-efficient synthesis of bifidocin A and provide a new perspective into the industrial production of bacteriocin.
细菌素是一种能有效抑制细菌的天然物质，但它的生产通常受到环境的限制。共培养是一种刺激细菌素产生的策略。双歧杆菌 BB04 产生的双歧菌素 A 是一种新型的广谱抗菌活性的食源性细菌素。为了提高双歧菌素 A 的产量，首先在共培养中筛选了细菌素诱导株。然后，通过转录组和蛋白质组分析研究了共培养诱导的分子机制。最后，通过靶向代谢组学技术鉴定了关键的诱导代谢物。结果表明，共培养中的异常威克汉姆酵母 Y-5 可以显著提高双歧菌素 A 的产量，比单培养提高了 3.00 倍。这种诱导作用可能不依赖于细胞的直接接触，而是由于持续暴露于特定浓度的诱导物质。在共培养中，异常威克汉姆酵母 Y-5 上调了 Hxk2 和 Tap42，激活了葡萄糖-cAMP 和 Tor 和 HOG-MAPK 途径，刺激了逆行基因的表达，产生了谷氨酰胺和甘油来维持活性。在此过程中，异常威克汉姆酵母 Y-5 产生的谷氨酰胺、肌苷、鸟苷、腺嘌呤、尿嘧啶、富马酸和丙酮酸可以诱导双歧菌素 A 的合成。总之，共培养中的异常威克汉姆酵母 Y-5 通过调节各种信号通路产生诱导物质来诱导双歧菌素 A 的合成。这些发现为高效合成双歧菌素 A 奠定了基础，并为细菌素的工业生产提供了新的视角。
