title: Improved propionic acid and 5,6-dimethylbenzimidazole control strategy for vitamin B12 fermentation by Propionibacterium freudenreichii.
abstract: 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.
authors.affiliation: 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. Electronic address: wangpeng506@sina.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: College of Chemical & Pharmaceutical Engineering, Hebei University of Science & Technology, Shijiazhuang 050018, China.
authors.forename: Youjing
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: State Key Laboratory Breeding Base-Hebei Province Key Laboratory of Molecular Chemistry for Drug, Hebei University of Science & Technology, Shijiazhuang 050018, China.
authors.forename: Shouxin
authors.initials: S
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, P.O. Box 353, Beijing 100190, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001562:Benzimidazoles / Q000494:pharmacology*; D019149:Bioreactors / Q000382:microbiology; D005285:Fermentation / Q000187:drug effects*; D011422:Propionates / Q000032:analysis / Q000378:metabolism*; D011424:Propionibacterium / Q000187:drug effects* / Q000378:metabolism*; D014805:Vitamin B 12 / Q000032:analysis / Q000378:metabolism*
chemical_list: D001562:Benzimidazoles; D011422:Propionates; C015158:5,6-dimethylbenzimidazole; C029658:propionic acid; D014805:Vitamin B 12
keywords: 5,6-Dimethylbenzimidazole; Expanded bed adsorption bioreactor; Feed-back inhibition; Propionic acid; Vitamin B12