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Real-time fluid dynamics investigation and physiological response for erythromycin fermentation scale-up from 50 L to 132 m3 fermenter

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Abstract

The physiological response of erythromycin fermentation scale-up from 50 L to 132 m3 scale was investigated. A relatively high oxygen uptake rate (OUR) in early phase of fermentation was beneficial for erythromycin biosynthesis. Correspondingly, the maximal consistency coefficient (K) reflecting non-Newtonian fluid characteristics in 50 L and 132 m3 fermenter also appeared in same phase. Fluid dynamics in different scale bioreactor was further investigated by real-time computational fluid dynamics modeling. The results of simulation showed that the impeller combination in 50 L fermenter could provide more modest flow field environment compared with that in 132 m3 fermenter. The decrease of oxygen transfer rate (OTR) in 132 m3 fermenter was the main cause for impairing cell physiological metabolism and erythromycin biosynthesis. These results were helpful for understanding the relationship between hydrodynamic environment and physiological response of cells in bioreactor during the scale-up of fermentation process.

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Abbreviations

\( d_{\text{b}} \) :

Mean diameter of bubbles (m)

\( D_{\text{L}} \) :

Oxygen diffusivity in liquid (m2/s)

D :

Impeller diameter (mm)

H :

Liquid height (mm)

K L :

Oxygen mass transfer coefficient in liquid membrane (m/s)

L :

Baffle length (mm)

N :

Rotating speed (rpm)

r :

Radial coordinate (m)

S :

Source item in N–S equation

T :

Tank diameter (mm)

t c :

Circulation time of cell through the impeller sweeping zone (s)

V L :

Bioreactor capacity (L)

w :

Baffle width (mm)

z :

z coordinate (m).

\( \phi_{\text{v}} \) :

Viscous dissipation function (1/s2)

μ :

Liquid viscosity (Pa s)

\( \tau \) :

Shear strain (Pa)

γ :

Shear strain rate (s)

ϕ :

Local volume fraction of the gas phase (m)

\( \varepsilon \) :

Local energy dissipation rate (w)

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Acknowledgments

This work was financially supported by a grant from the National Scientific and Technological Major Special Project (Significant Creation of New drugs), No. 2011ZX09203-001-03, and the Major State Basic Research Development Program of China (973 Program), No. 2007CB714303.

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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

    Xiang Zou, Jian-ye Xia, Ju Chu, Ying-ping Zhuang & Si-liang Zhang

  2. College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, People’s Republic of China

    Xiang Zou

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  1. Xiang Zou
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  2. Jian-ye Xia
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  3. Ju Chu
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  4. Ying-ping Zhuang
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  5. Si-liang Zhang
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Corresponding author

Correspondence to Ju Chu.

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X. Zou and J. Xia contributed equally to this work.

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Zou, X., Xia, Jy., Chu, J. et al. Real-time fluid dynamics investigation and physiological response for erythromycin fermentation scale-up from 50 L to 132 m3 fermenter. Bioprocess Biosyst Eng 35, 789–800 (2012). https://doi.org/10.1007/s00449-011-0659-z

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  • DOI: https://doi.org/10.1007/s00449-011-0659-z

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