Performance of Propionibacterium freudenreichii in anaerobic, aerobic and periodic fermentations were studied. It was found that oxygen is a key parameter to the metabolic regulation. Cells could grow faster during a short period (6 h) after a DO-shift. However, long time aerobic fermentation (over 6 h) is disadvantageous in cell growth due to the inhibition of oxygen on the synthesis of cytochromes. The propionate was decomposed immediately and pyruvate was accumulated after DO-shift. Low DO concentration was found to be advantageous in cell growth, in decomposition of propionate, and in lowering the production of acetate, A novel cyclic operation where anaerobic and aerobic conditions were alternately implemented was developed to take full advantages of anaerobic and aerobic fermentations in order to enhance the production of vitamin B-12. Propionate was significantly produced and no pyruvate was accumulated in the anaerobic cycle, whilst propionate was decomposed and pyruvate was accumulated in the aerobic cycle. Vitamin B-12 was synthesized in the anaerobic cycle and ceased to be produced in the aerobic cycle. With this operation mode, a low concentration of propionate could be maintained and high cell concentration could be attained. The volumetric production of vitamin B-12 using this method could be increased by about 2-fold as compared with that attained in the anaerobic fermentation.