Xu Dongmei, Wang Yaoyao, Li Hongzhen, Wang Bing, Chai Libin, Feng Li, Ren Fengzhi, Zhao Xuejin, Zhang Xuexia
Hebei Vocational University of Industry and Technology, Shijiazhuang, 050091, China.
New Drug Research & Development Center of North China Pharmaceutical Group Corporation, National Engineering Research Center of Microbial Medicine, Shijiazhuang, 052165, China.
Microb Cell Fact. 2024 Dec 31;23(1):350. doi: 10.1186/s12934-024-02632-6.
Rapamycin is an important natural macrolide antibiotic with antifungal, immunosuppressive and antitumor activities produced by Streptomyces rapamycinicus. However, their prospective applications are limited by low fermentation units. In this study, we found that the exogenous aromatic amino acids phenylalanine and tyrosine could effectively increase the yield of rapamycin in industrial microbial fermentation. To gain insight into the mechanism of rapamycin overproduction, comparative transcriptomic profiling was performed between media with and without phenylalanine and tyrosine addition. The results showed that the addition of phenylalanine and tyrosine upregulated the transcription levels of genes involved in rapamycin biosynthesis, precursor production, and transporters. In addition, the transcription levels of many carbohydrate metabolism-related genes were down-regulated, leading to a decrease in growth, suggesting that balancing cell growth and rapamycin biosynthesis may be important to promote efficient biosynthesis of rapamycin in Streptomyces rapamycinicus. These results provide a basis for understanding physiological roles of phenylalanine and tyrosine, and a new way to increase rapamycin production in Streptomyces cultures.
雷帕霉素是一种由雷帕霉素链霉菌产生的具有抗真菌、免疫抑制和抗肿瘤活性的重要天然大环内酯类抗生素。然而，它们的潜在应用受到低发酵单位的限制。在本研究中，我们发现外源芳香族氨基酸苯丙氨酸和酪氨酸可有效提高工业微生物发酵中雷帕霉素的产量。为深入了解雷帕霉素过量生产的机制，我们在添加和不添加苯丙氨酸及酪氨酸的培养基之间进行了比较转录组分析。结果表明，苯丙氨酸和酪氨酸的添加上调了参与雷帕霉素生物合成、前体产生和转运体的基因的转录水平。此外，许多与碳水化合物代谢相关的基因的转录水平下调，导致生长下降，这表明平衡细胞生长和雷帕霉素生物合成可能对促进雷帕霉素链霉菌中雷帕霉素的高效生物合成很重要。这些结果为理解苯丙氨酸和酪氨酸的生理作用提供了基础，并为提高链霉菌培养物中雷帕霉素产量提供了新途径。
