| Autor: |
Huang Xie, Yi-Ting Su, Qing-Ting Bu, Yue-Ping Li, Qing-Wei Zhao, Yi-Ling Du, Yong-Quan Li |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Synthetic and Systems Biotechnology, Vol 9, Iss 4, Pp 766-774 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2405-805X |
| DOI: |
10.1016/j.synbio.2024.06.004 |
| Popis: |
The anti-Clostridium difficile infection (CDI) drug fidaxomicin is a natural polyketide metabolite mainly produced by Micromonosporaceae, such as Actinoplanes deccanensis, Dactylosporangium aurantiacum, and Micromonospora echinospora. In the present study, we employed a stepwise strategy by combining heterologous expression, chassis construction, promoter engineering, activator and transporters overexpression, and optimization of fermentation media for high-level production of fidaxomicin. The maximum yield of 384 mg/L fidaxomicin was achieved with engineered Streptomyces albus D7-VHb in 5 L-tank bioreactor, and it was approximately 15-fold higher than the native strain Actinoplanes deccanensis YP-1 with higher strain stability and growth rate. This study developed an enhanced chassis strain, and for the first time, achieved the heterologous synthesis of fidaxomicin through a combinatorial metabolic engineering strategy. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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