Construction of Inducible Genetic Switch for the Global Regulator WblA To Sustain Both Overproduction of Tiancimycins and On-Demand Sporulation in Streptomyces sp. CB03234
| Autor: | Yanwen Duan, Die Gao, Zhoukang Zhuang, Manxiang Zhu, Xiangcheng Zhu, Fan Zhang, Jing Lin |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
0303 health sciences biology Biomedical Engineering Regulator General Medicine biology.organism_classification 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Streptomyces Cell biology Transcriptome 03 medical and health sciences 010608 biotechnology On demand Overproduction 030304 developmental biology |
| Zdroj: | ACS Synthetic Biology. 9:1460-1467 |
| ISSN: | 2161-5063 |
| DOI: | 10.1021/acssynbio.0c00114 |
| Popis: | The complex life cycle of streptomycetes is closely related to their secondary metabolisms, all controlled by cascade regulations. Tiancimycins (TNMs) are ten-membered enediynes possessing great potential for antitumor drug development. However, their low yields in Streptomyces sp. CB03234 have greatly limited subsequent studies. Through transcriptome analysis and genetic characterization, we proved that WblA is one pivotal global regulator to repress the biosynthesis of TNMs. The deletion of wblA could significantly enhance the production of TNMs, but also abolish the sporulation in CB03234. By constructing the NitR-e-caprolactam inducible genetic switch, the expression of wblA was governed in CB03234-NRW, thereby sustaining the overproduction of TNMs and recovering the normal sporulation upon induction, which were practical for the scaled-up production of TNMs. Considering the prevalence and conserved regulatory roles of WblA in streptomycetes, our developed strategy shall provide an effective and practical approach to facilitate titer improvement and discovery of natural products. |
| Databáze: | OpenAIRE |
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