Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis
Abstract 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...
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| Format: | Article |
| Language: | English |
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BMC
2024-12-01
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| Series: | Microbial Cell Factories |
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| Online Access: | https://doi.org/10.1186/s12934-024-02632-6 |
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| author | Dongmei Xu Yaoyao Wang Hongzhen Li Bing Wang Libin Chai Li Feng Fengzhi Ren Xuejin Zhao Xuexia Zhang |
| author_facet | Dongmei Xu Yaoyao Wang Hongzhen Li Bing Wang Libin Chai Li Feng Fengzhi Ren Xuejin Zhao Xuexia Zhang |
| author_sort | Dongmei Xu |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-3d29e851ee1c4a8db00d322534334289 |
| institution | Kabale University |
| issn | 1475-2859 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj-art-3d29e851ee1c4a8db00d3225343342892025-01-05T12:50:45ZengBMCMicrobial Cell Factories1475-28592024-12-0123111110.1186/s12934-024-02632-6Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysisDongmei Xu0Yaoyao Wang1Hongzhen Li2Bing Wang3Libin Chai4Li Feng5Fengzhi Ren6Xuejin Zhao7Xuexia Zhang8Hebei Vocational University of Industry and TechnologyNew Drug Research & Development Center of North China Pharmaceutical Group Corporation, National Engineering Research Center of Microbial MedicineNew Drug Research & Development Center of North China Pharmaceutical Group Corporation, National Engineering Research Center of Microbial MedicineHebei Vocational University of Industry and TechnologyNew Drug Research & Development Center of North China Pharmaceutical Group Corporation, National Engineering Research Center of Microbial MedicineHebei Vocational University of Industry and TechnologyNew Drug Research & Development Center of North China Pharmaceutical Group Corporation, National Engineering Research Center of Microbial MedicineCAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of SciencesNew Drug Research & Development Center of North China Pharmaceutical Group Corporation, National Engineering Research Center of Microbial MedicineAbstract 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.https://doi.org/10.1186/s12934-024-02632-6RapamycinStreptomycesPhenylalanine and tyrosineTranscriptome |
| spellingShingle | Dongmei Xu Yaoyao Wang Hongzhen Li Bing Wang Libin Chai Li Feng Fengzhi Ren Xuejin Zhao Xuexia Zhang Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis Microbial Cell Factories Rapamycin Streptomyces Phenylalanine and tyrosine Transcriptome |
| title | Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis |
| title_full | Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis |
| title_fullStr | Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis |
| title_full_unstemmed | Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis |
| title_short | Insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of Streptomyces rapamycinicus with transcriptome analysis |
| title_sort | insights into the roles of exogenous phenylalanine and tyrosine in improving rapamycin production of streptomyces rapamycinicus with transcriptome analysis |
| topic | Rapamycin Streptomyces Phenylalanine and tyrosine Transcriptome |
| url | https://doi.org/10.1186/s12934-024-02632-6 |
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