4.5 Article

Controlling the feed rate of propanol to optimize erythromycin fermentation by on-line capacitance and oxygen uptake rate measurement

Journal

BIOPROCESS AND BIOSYSTEMS ENGINEERING
Volume 39, Issue 2, Pages 255-265

Publisher

SPRINGER
DOI: 10.1007/s00449-015-1509-1

Keywords

Erythromycin; Propanol; On-line capacitance measurement; OUR; Fermentation

Funding

  1. National Natural Science Foundation of China [21276081]
  2. Major State Basic Research Development Program of China (973 Program) [2012CB721006]
  3. National Scientific and Technological Major Special Project (Significant Creation of New drugs) [2011ZX09203-001-03]
  4. Research Fund for Doctoral Program of Higher Education of China [20110074110015]

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The aim of the present study was to optimize the feeding proportion of glucose and propanol for erythromycin biosynthesis by real-time monitoring and exploring its limited ratio by the on-line multi-frequency permittivity measurement. It was found that the capacitance values were sensitive to the variation of biomass concentration and microbial morphology as well as the true state of cell growth. It was most favorable to both cell growth and secondary metabolism to keep the ratio of glucose to propanol at 4.3 (g/g). The specific growth rate calculated by the capacitance measurement correctly and accurately reflected the cell physiological state. An appropriate feed rate of propanol was crucial for cell growth and secondary metabolism, as well as to improve the quality of erythromycin-A. In addition, the erythromycin production titer (10,950 U/mL) was further enhanced by 4 % when the propanol feed was regulated by step-down strategy based on both OUR (oxygen uptake rate) and the on-line monitoring capacitance.

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