Bioprocess Strategies for Vitamin B12 Production by Microbial Fermentation and Its Market Applications

Abstract

Vitamin B₁₂ is a widely used compound in the feed and food, healthcare and medical industries that can only be produced by fermentation because of the complexity of its chemical synthesis. For this reason, finding better producer strains and optimizing their bioprocesses have been the main focus of industrial producers over the last few decades. In this review, we initially provide a historical overview of vitamin B₁₂ research and the main biosynthetic characteristics of the two microorganism families typically used for its industrial production: several strains of Propionibacterium freudenreichii and strains related to Pseudomonas denitrificans. Later, a complete summary of the current state of vitamin B₁₂ industrial production as well as the main advances and challenges for improving it is detailed, with a special focus on bioprocess optimization, which aims not only to increase production but also sustainability. In addition, a comprehensive list of the most important and relevant patents for the present industrial strains is provided. Finally, the potential applications of vitamin B₁₂ in different markets are discussed.

Keywords: Propionibacterium freudenreichii; Pseudomonas denitrificans; cobalamin; cyanocobalamin production.

Figure 1

Schematical representation of the structure shared by all cobalamin isoforms. The main groups that usually act as the upper ligand are also shown. 5,6-DMBI: 5,6-dimethylbenzimidazole.

Figure 2

Summary of anaerobic and aerobic adenosylcobalamin biosynthesis. Genes encoding the proteins from the aerobic and anaerobic pathways are shown in blue and red, respectively, except for Protein α whose coding gene is not known.

Figure 3

Classical bioprocess to obtain highly pure Cyanocobalamin. The main CNCbl stream is highlighted in red. Intermediate storage vessels are omitted to simplify the figure. P1 to P11 represent Process 1 to Process 11, respectively. Bioprocess represented using SuperPro Designer^® V9 Academic Site Edition, Intelligen, Inc. (Scotch Plains, NJ, USA).