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Combined available nitrogen resources enhanced erythromycin production and preliminary exploration of metabolic flux analysis under nitrogen perturbations

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Abstract

In the current study, the effect of different available nitrogen sources on erythromycin fermentation by Saccharopolyspora erythraea No. 8 is evaluated. Three different combinations of corn steep liquor and yeast powder were developed to investigate their impacts on erythromycin production. The results indicate that the optimal combination of available nitrogen sources was 10.0 g/L corn steep liquor and 4.0 g/L yeast power, generating a maximum yield of erythromycin of 13672 U/mL. To explore the effects of nitrogen perturbations on cell metabolism, metabolic flux analyses were performed and compared under different conditions. A high flux pentose phosphate pathway provided more NADPH for erythromycin synthesis via nitrogen optimization. Moreover, high n-propanol specific consumption rate enhanced erythromycin synthesis and n-propanol flowed into the central carbon metabolism by methylmalonyl-CoA node. These results indicate that the selection of an appropriate organic nitrogen source is essential for cell metabolism and erythromycin synthesis, and this is the first report of the successful application of available nitrogen source combinations in industrial erythromycin production.

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Acknowledgements

This work was financially supported by the National Key Research and Development Program (2017YFB0309302), the National Basic Research Program of China (973 Program) (No. 2012CB721006), National Natural Science Foundation of China (No. 21276081) and the Fundamental Research Funds for the Central Universities (22221818014).

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Authors and Affiliations

  1. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, P.O.box 329#, 130 Meilong Road, Shanghai, 200237, People’s Republic of China

    Qi Zhang, Haifeng Hang, ** Zhuang & Ju Chu

  2. Yidu HEC Biochem. Co. Ltd., Yidu, 443300, Hubei, People’s Republic of China

    Wei Zeng, Zhenhua Yu & **aojian Wang

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  1. Qi Zhang
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  2. Haifeng Hang
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  3. **wei Tian
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  4. Wei Zeng
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  8. Ying** Zhuang
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Correspondence to Ying** Zhuang or Ju Chu.

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Zhang, Q., Hang, H., Tian, X. et al. Combined available nitrogen resources enhanced erythromycin production and preliminary exploration of metabolic flux analysis under nitrogen perturbations. Bioprocess Biosyst Eng 42, 1747–1756 (2019). https://doi.org/10.1007/s00449-019-02171-0

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  • DOI: https://doi.org/10.1007/s00449-019-02171-0

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