Improvement of vitamin B₁₂ fermentation by reducing the inhibitory metabolites by cell recycle system and a mixed culture

The major problem in vitamin B₁₂ production using Propionibacterium is the growth inhibition of the cell due to the accumulation of inhibitory metabolites such as propionic acid and acetic acid. In the present paper, we considered several approaches of controlling the propionic acid concentration at low level. Namely: (1) the periodic cultivation of Propionibacterium where dissolved oxygen (DO) concentration was alternatively changed between 0 and 1 ppm; (2) cell recycle system using hollow fiber module; and (3) mixed culture using Propionibacterium and Ralstonia eutropha where the latter microorganism assimilates the propionic acid produced by the former. It was found that the productivity of vitamin B₁₂ was the highest for the cell recycle system, while if the performance was evaluated based on the amount of vitamin B₁₂ produced per medium used, the mixed culture system gave the far highest value. (C) 2000 Elsevier Science S.A.