Wang Peng, Zhang Zhiwei, Jiao Youjing, Liu Shouxin, Wang Yunshan
College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, China; Hebei Research Center of Pharmaceutical and Chemical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, China; State Key Laboratory Breeding Base-Hebei Province Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science & Technology, Shijiazhuang 050018, China.
College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, China.
J Biotechnol. 2015 Jan 10;193:123-9. doi: 10.1016/j.jbiotec.2014.11.019. Epub 2014 Nov 29.
An efficient fermentation-strengthening approach was developed to improve the anaerobic production of vitamin B12 by cultivation process optimization with Propionibacterium freudenreichii. The effects of the byproduct propionic acid and the precursor 5,6-dimethylbenzimidazole (DMB) on vitamin B12 biosynthesis were investigated. Byproduct inhibition experiments showed that maintaining propionic acid concentration in broth below 10-20 g/L in the early stage and 20-30 g/L in the late stage can efficiently improve vitamin B12 biosynthesis. Batch fermentation indicated the occurrence of feed-back inhibition in intracellular intermediate biosynthesis. In addition, the incorporation of the precursor DMB depended on the fermentation level of the vitamin B12 intermediate. High vitamin B12 concentration (58.8 mg/L) and production (0.37 mg/g) were obtained with an expanded bed adsorption bioreactor by using the propionic acid and DMB control method. The optimum concentration and production of 59.5 and 0.59 mg/L h for vitamin B12 production were respectively achieved after five continuous batches.
开发了一种有效的强化发酵方法，通过对费氏丙酸杆菌的培养过程进行优化，提高维生素B12的厌氧产量。研究了副产物丙酸和前体5,6-二甲基苯并咪唑（DMB）对维生素B12生物合成的影响。副产物抑制实验表明，在前期将发酵液中丙酸浓度维持在10-20 g/L以下，后期维持在20-30 g/L，可以有效提高维生素B12的生物合成。分批发酵表明细胞内中间产物生物合成中存在反馈抑制。此外，前体DMB的掺入取决于维生素B12中间产物的发酵水平。通过使用丙酸和DMB控制方法，在膨胀床吸附生物反应器中获得了高维生素B12浓度（58.8 mg/L）和产量（0.37 mg/g）。经过五个连续批次后，维生素B12产量分别达到了最佳浓度和产量59.5和0.59 mg/L·h。
