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

  • Qi Zhang
  • Haifeng Hang
  • Xiwei Tian
  • Wei Zeng
  • Zhenhua Yu
  • Xiaojian Wang
  • Yin Tang
  • Yingping ZhuangEmail author
  • Ju ChuEmail author
Research Paper
  • 36 Downloads

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.

Keywords

Erythromycin Available nitrogen sources Corn steep liquor Yeast powder Metabolic flux 

Notes

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).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

449_2019_2171_MOESM1_ESM.doc (52 kb)
Biochemical reactions in the metabolic model (DOC 51 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Qi Zhang
    • 1
  • Haifeng Hang
    • 1
  • Xiwei Tian
    • 1
  • Wei Zeng
    • 2
  • Zhenhua Yu
    • 2
  • Xiaojian Wang
    • 2
  • Yin Tang
    • 1
  • Yingping Zhuang
    • 1
    Email author
  • Ju Chu
    • 1
    Email author
  1. 1.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiPeople’s Republic of China
  2. 2.Yidu HEC Biochem. Co. Ltd.YiduPeople’s Republic of China

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