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

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 was 2.1 and 7.02 times of that at 18.23 min. 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. 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.