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Metabolic engineering of Escherichia coli for the production of (R)-α-lipoic acid

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Abstract

Objective

To increase the production of (R)-α-lipoic acid directly from octanoic acid using engineered Escherichia coli with the regeneration of S-adenosylmethionine.

Results

The biosynthesis of (R)-α-lipoic acid (LA) in E. coli BL21(DE3) is improved by co-expression of lipoate-protein ligase A (LplA) from E. coli MG1655 and lipoate synthase (LipA) from Vibrio vulnificus. The engineered strain produces 20.99 µg l−1 of LA in shake flask cultures. The titers of LA are increased to 169.28 µg l−1 after the optimization of the medium components and fermentation conditions. We find that the [4Fe-4S] cluster is important for the activity of LipA and co-expression of iscSUA promotes the regeneration of the [4Fe-4S] cluster and leads to the highest LA titer of 589.30 µg l−1.

Conclusion

The method described here can be widely applied for the biosynthesis of (R)-α-lipoic acid and other metabolites.

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Acknowledgements

We would like to thank Dr. Jianmin Yang, Dr. Yunquan Zheng, Dr. Feng Li, Dr. Mingmao Chen, and Dr. Li Chen for their helpful discussion and suggestions.

Supplementary information

Supplementary Table S1-3 and Supplementary Figure S1-5 can be found in the Supplementary material.

Funding

This work was supported by the National Natural Science Foundation of China (32001037), the Natural Science Foundation of Fujian Province (2020J01491), Fuzhou University Research Fund (GXRC-20033).

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Authors and Affiliations

  1. College of Biological Science and Engineering, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China

    Jianbin Xiao, Shaobin Guo & Xian’ai Shi

  2. Fujian Key Lab of Medical Instrument and Biopharmaceutical Technology, Fuzhou University, No. 2 Xueyuan Road, Fuzhou, 350108, China

    Xian’ai Shi

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  1. Jianbin Xiao
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Contributions

JX, SG, and XS conceived and designed the research. JX conducted experiments. JX, SG, and XS analyzed data. JX wrote the manuscript. SG revised the manuscript. All authors read and approved the manuscript.

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Correspondence to Shaobin Guo.

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Xiao, J., Guo, S. & Shi, X. Metabolic engineering of Escherichia coli for the production of (R)-α-lipoic acid. Biotechnol Lett 45, 273–286 (2023). https://doi.org/10.1007/s10529-022-03341-z

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  • DOI: https://doi.org/10.1007/s10529-022-03341-z

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