Bioprocess and Biosystems Engineering

, Volume 34, Issue 7, pp 789–793 | Cite as

Production of nattokinase by high cell density fed-batch culture of Bacillus subtilis

  • Eun-Yeong Kwon
  • Kyung Mi Kim
  • Mi Kyoung Kim
  • In Young Lee
  • Beom Soo Kim
Original Paper


Bacillus subtilis was cultivated to high cell density for nattokinase production by pH-stat fed-batch culture. A concentrated mixture solution of glucose and peptone was automatically added by acid-supplying pump when culture pH rose above high limit. Effect of the ratio of glucose to peptone in feeding solution was investigated on cell growth and nattokinase production by changing the ratio from 0.2 to 5 g glucose/g peptone. The highest cell concentration was 77 g/L when the ratio was 0.2 g glucose/g peptone. Cell concentration decreased with increasing the ratio of glucose to peptone in feeding solution, while the optimum condition existed for nattokinase production. The highest nattokinase activity was 14,500 unit/mL at a ratio of 0.33 g glucose/g peptone, which was 4.3 times higher than that in batch culture.


Nattokinase Bacillus subtilis Fed-batch culture High cell density culture 



This research was financially supported by the Ministry of Knowledge Economy (MKE) and Korea Institute for Advancement in Technology (KIAT) through the Workforce Development Program in Strategic Technology.


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Eun-Yeong Kwon
    • 1
  • Kyung Mi Kim
    • 2
  • Mi Kyoung Kim
    • 2
  • In Young Lee
    • 2
  • Beom Soo Kim
    • 1
  1. 1.Department of Chemical EngineeringChungbuk National UniversityCheongjuKorea
  2. 2.DMJ Biotech CorpYeongiKorea

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