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Engineering the methyltransferase through inactivation of the genK and genL leads to a significant increase of gentamicin C1a production in an industrial strain of Micromonospora echinospora 49-92S

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Abstract

In this study, a single-component high-yielding Micromonospora echinospora strain 49-92S-KL01 was constructed by deleting methyltransferase-encoding genes genK and genL. In 5-L fermentation trials, gentamicin C1a titers in the mutant strain were 3.22-fold higher than that in the parental strain (211 U/mL vs. 50 U/mL). The glycolysis pathway and tricarboxylic acid cycle fluxes were reduced by 26.8% and 26.6%, respectively, compared to the parental strain according to the metabolic flux analysis during the stationary phase, resulting in lower levels of energy supplements required for the cellular maintenance. Meanwhile, a significant enhancement in precursor (paromamine) accumulation and availability was observed in 49-92S-KL01 compared to parental strain. These results indicate that genK and genL significantly affect the synthesis of gentamicin C1a. In addition, this study provides a more rational strategy for gentamicin C1a production.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was financially supported by a grant from the National Key Research and Development Program of China (No. 2019YFA0904800). Meanwhile, this work was financially supported by an education cooperation fund from the Yihai Kerry Arawana Holdings Co., Ltd.

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Feng Xu, Xinyu Zhang, Ling Liu, Xiang Ke, Jie Wu, Yuanxin Guo, Xiwei Tian & Ju Chu

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  1. Feng Xu
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  2. Xinyu Zhang
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  3. Ling Liu
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  7. Xiwei Tian
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  8. Ju Chu
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Contributions

Conceptualization: [XT, JC]; methodology: [FX, XZ]; formal analysis and investigation: [FX, XZ, JW]; writing—original draft preparation: [FX, XZ]; writing—review and editing: [XK, LL, XT, JC]; funding acquisition: [XT, JC]; supervision: [XT, JC].

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Correspondence to Xiwei Tian or Ju Chu.

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Xu, F., Zhang, X., Liu, L. et al. Engineering the methyltransferase through inactivation of the genK and genL leads to a significant increase of gentamicin C1a production in an industrial strain of Micromonospora echinospora 49-92S. Bioprocess Biosyst Eng 45, 1693–1703 (2022). https://doi.org/10.1007/s00449-022-02774-0

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