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用于高效表达重组FGF21的双启动子和串联基因策略

Double promoter and tandem gene strategy for efficiently expressing recombinant FGF21.

作者信息

Liu Longying, Ning Nuoyi, Xu Simeng, Chen Dongqing, Zhou Luping, Guo Zhimou, Liang Xinmiao, Ye Xianlong

机构信息

Ganjiang Chinese Medicine Innovation Center, Nanchang, 330000, China.

Dalian Institute of Chemical Physics, Key Laboratory of Separation Science for Analytical Chemistry, Chinese Academy of Sciences, Zhongshan Road 457, Dalian, 116023, China.

出版信息

Microb Cell Fact. 2024 Jun 12;23(1):171. doi: 10.1186/s12934-024-02447-5.

DOI:10.1186/s12934-024-02447-5
PMID:38867280
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11167883/
Abstract

BACKGROUND

Fibroblast growth factor 21 (FGF21) is a promising candidate for treating metabolic disorder diseases and has been used in phase II clinical trials. Currently, metabolic diseases are prevalent worldwide, underscoring the significant market potential of FGF21. Therefore, the production of FGF21 must be effectively improved to meet market demand.

RESULTS

Herein, to investigate the impact of vectors and host cells on FGF21 expression, we successfully engineered strains that exhibit a high yield of FGF21. Surprisingly, the data revealed that vectors with various copy numbers significantly impact the expression of FGF21, and the results showed a 4.35-fold increase in expression levels. Furthermore, the performance of the double promoter and tandem gene expression construction design surpassed that of the conventional construction method, with a maximum difference of 2.67 times.

CONCLUSION

By exploring engineered vectors and host cells, we successfully achieved high-yield production of the FGF21 strain. This breakthrough lays a solid foundation for the future industrialization of FGF21. Additionally, FGF21 can be easily, quickly and efficiently expressed, providing a better tool and platform for the research and application of more recombinant proteins.

摘要

背景

成纤维细胞生长因子21(FGF21)是治疗代谢紊乱疾病的一个有前景的候选药物,已进入II期临床试验。目前,代谢性疾病在全球普遍存在,这凸显了FGF21巨大的市场潜力。因此,必须有效提高FGF21的产量以满足市场需求。

结果

在此,为了研究载体和宿主细胞对FGF21表达的影响,我们成功构建了FGF21高产菌株。令人惊讶的是,数据显示不同拷贝数的载体对FGF21的表达有显著影响,表达水平提高了4.35倍。此外,双启动子和串联基因表达构建设计的性能超过了传统构建方法,最大差异为2.67倍。

结论

通过探索工程载体和宿主细胞,我们成功实现了FGF21菌株的高产。这一突破为FGF21未来的工业化奠定了坚实基础。此外,FGF21能够轻松、快速且高效地表达,为更多重组蛋白的研究和应用提供了更好的工具和平台。

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Use of FGF21 analogs for the treatment of metabolic disorders: a systematic review and meta-analysis.使用 FGF21 类似物治疗代谢紊乱:系统评价和荟萃分析。
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用于多步生物合成途径的双诱导控制系统。
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