Bioprocess and Biosystems Engineering

, Volume 42, Issue 5, pp 817–827 | Cite as

Intracellular response of Bacillus natto in response to different oxygen supply and its influence on menaquinone-7 biosynthesis

  • Xiao-chen Ma
  • Si-yu Zhu
  • Miao-miao Luo
  • Xue-chao Hu
  • Cheng Peng
  • He Huang
  • Lu-Jing RenEmail author
Research Paper


Menaquinone-7 (MK-7) plays an important role in blood clotting, cardiovascular disease and anti-osteoporosis, and has been wildly used in the food additives and pharmaceutical industries. The aim of this study was to investigate the mechanism of menaquinone-7 biosynthesis in response to different oxygen supplies in Bacillus natto. The differences of fermentation performance, intracellular metabolites, oxidative stress reaction and enzyme activities of Bacillus natto R127 were analyzed under different KLa. Glycerol consumption rate and MK-7 yield at 24.76 min− 1 was 2.1 and 7.02 times of that at 18.23 min− 1. Oxidative stress analysis showed the cell generated more active oxygen and possessed higher antioxidant capacity at high oxygen supply condition. Meanwhile, high pyruvate kinase and high cytochrome c oxidase activities were also observed at 24.76 min− 1. Furthermore, comparative metabolomics analyses concluded series of biomarkers for high MK-7 biosynthesis and cell rapid growth. Besides, several metabolic responses including low glyceraldehyde-3-phosphate accumulation, low flux from pyruvate to lactic acid, high active TCA pathway, were also found to be associated with high MK-7 accumulation at high oxygen supply conditions. These findings provided the information for better understanding of oxygen effect on MK-7 biosynthesis and lay a foundation for further improvement of MK-7 production as well.

Graphical abstract


Bacillus natto Menaquinone-7 Metabonomics Oxygen Enzyme assay 



This work was financially supported by the National Natural Science Foundation of China (No. 21878151), the Outstanding Youth Foundation of Jiangsu Nature Science Foundation (BK20160092), the Program for Innovative Research Team in University of Jiangsu Province (2015), the General Program on Natural Science Research Project of Higher Education of Jiangsu (18KJB530007) and the support of Jiangsu Synergetic Innovation Center for Advanced Bio-Manufacture (XTE1829).

Supplementary material

Supplementary material 1 (DOC 365 KB)


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Copyright information

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

Authors and Affiliations

  • Xiao-chen Ma
    • 1
  • Si-yu Zhu
    • 2
  • Miao-miao Luo
    • 2
  • Xue-chao Hu
    • 2
  • Cheng Peng
    • 2
  • He Huang
    • 3
    • 4
  • Lu-Jing Ren
    • 2
    • 4
    Email author
  1. 1.Institute of MicrobiologyChinese Academy of SciencesBeijingPeople’s Republic of China
  2. 2.College of Biotechnology and Pharmaceutical EngineeringNanjing Tech UniversityNanjingPeople’s Republic of China
  3. 3.School of Pharmaceutical SciencesNanjing Tech UniversityNanjingPeople’s Republic of China
  4. 4.Jiangsu National Synergetic Innovation Center for Advanced MaterialsNanjingPeople’s Republic of China

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