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The Improvement of Epothilone D Yield by the Disruption of epoK Gene in Sorangium cellulosum Using TALEN System

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Abstract

Epothilones are a kind of 16-member macrolides with strong anticancer activity, which was produced by Sorangium cellulosum. Epothlione D shows better drug resistance and safety than taxol in clinical trials. However, the low yield of epothilone D in Sorangium cellulosum and thereof toxicity limited the application of epothilone D. In this study, the epoK gene in gene cluster for epothilone was firstly inactivated by the employment of TALEN gene knockout system. The qRT-PCR analysis and sequencing were performed to confirm the gene deletion of epoK, resulting in the epothilone D yield improvement by 34.9±1.6% and the decrease of epothilone B yield by 34.2±2.5%, which was demonstrated by LC–MS analysis. This study would lay a foundation for the yield improvement of epothilones D, B and thereof derivatives in S. cellulosum by genetic engineering, thus promoting the applications of epothilones in the field of anticancer.

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Data Availability

The authors declare that all data supporting the findings of this study are available within the article.

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Acknowledgements

We also thank Ye Zhenggui for his help.

Funding

This research was funded by the National Natural Science Foundation of China (Grant Nos. 31500037, 31800063, 41906106), the Natural Science Foundation of Guangdong province (2019A1515011829, 2019A1515011702), the GDAS Project of Science and Technology Development (2020GDASYL-20200105001), and the Guangdong Special Support Program (2019TQ05Y375).

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  1. Wei Ye and Taomei Liu have contributed equally to this manuscript.

Authors and Affiliations

  1. State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China

    Wei Ye, Taomei Liu, Wei-Min Zhang, Weiyang Zhang & Saini Li

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  1. Wei Ye
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Contributions

WY and WMZ conceived and designed the research and revised the manuscript. WY and TML conducted the experiments. SNL and HHL contributed strains. WY, TML, and WYZ analyzed the data. WY wrote the manuscript. . All authors read and approved the manuscript.

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Correspondence to Wei-Min Zhang.

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Ye, W., Liu, T., Zhang, WM. et al. The Improvement of Epothilone D Yield by the Disruption of epoK Gene in Sorangium cellulosum Using TALEN System. Mol Biotechnol 65, 282–289 (2023). https://doi.org/10.1007/s12033-022-00602-0

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