التفاصيل البيبلوغرافية
| العنوان: |
Enhancement of acarbose production by genetic engineering and fed-batch fermentation strategy in Actinoplanes sp. SIPI12-34 |
| المؤلفون: |
Zhenxin Li, Songbai Yang, Zhengyu Zhang, Yuanjie Wu, Jiawei Tang, Luoju Wang, Shaoxin Chen |
| المصدر: |
Microbial Cell Factories, Vol 21, Iss 1, Pp 1-14 (2022) |
| بيانات النشر: |
BMC, 2022. |
| سنة النشر: |
2022 |
| المجموعة: |
LCC:Microbiology |
| مصطلحات موضوعية: |
Acarbose, Actinoplanes sp., Transcriptome analysis, Genetic engineering, Multiple strategies, Fed-batch fermentation, Microbiology, QR1-502 |
| الوصف: |
Abstract Background Acarbose, as an alpha-glucosidase inhibitor, is widely used clinically to treat type II diabetes. In its industrial production, Actinoplanes sp. SE50/110 is used as the production strain. Lack of research on its regulatory mechanisms and unexplored gene targets are major obstacles to rational strain design. Here, transcriptome sequencing was applied to uncover more gene targets and rational genetic engineering was performed to increase acarbose production. Results In this study, with the help of transcriptome information, a TetR family regulator (TetR1) was identified and confirmed to have a positive effect on the synthesis of acarbose by promoting the expression of acbB and acbD. Some genes with low expression levels in the acarbose biosynthesis gene cluster were overexpressed and this resulted in a significant increase in acarbose yield. In addition, the regulation of metabolic pathways was performed to retain more glucose-1-phosphate for acarbose synthesis by weakening the glycogen synthesis pathway and strengthening the glycogen degradation pathway. Eventually, with a combination of multiple strategies and fed-batch fermentation, the yield of acarbose in the engineered strain increased 58% compared to the parent strain, reaching 8.04 g/L, which is the highest fermentation titer reported. Conclusions In our research, acarbose production had been effectively and steadily improved through genetic engineering based on transcriptome analysis and fed-batch culture strategy. Graphical Abstract |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1475-2859 |
| Relation: |
https://doaj.org/toc/1475-2859 |
| DOI: |
10.1186/s12934-022-01969-0 |
| URL الوصول: |
https://doaj.org/article/8acc4a9bb6e5417dac211b381dbcaf8f |
| رقم الانضمام: |
edsdoj.8acc4a9bb6e5417dac211b381dbcaf8f |
| قاعدة البيانات: |
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