Microbial and Genetic Resources for Cobalamin (Vitamin B12) Biosynthesis: From Ecosystems to Industrial Biotechnology

Abstract

Many microbial producers of coenzyme B12 family cofactors together with their metabolically interdependent pathways are comprehensively studied and successfully used both in natural ecosystems dominated by auxotrophs, including bacteria and mammals, and in the safe industrial production of vitamin B12. Metabolic reconstruction for genomic and metagenomic data and functional genomics continue to mine the microbial and genetic resources for biosynthesis of the vital vitamin B12. Availability of metabolic engineering techniques and usage of affordable and renewable sources allowed improving bioprocess of vitamins, providing a positive impact on both economics and environment. The commercial production of vitamin B12 is mainly achieved through the use of the two major industrial strains, Propionobacterium shermanii and Pseudomonas denitrificans, that involves about 30 enzymatic steps in the biosynthesis of cobalamin and completely replaces chemical synthesis. However, there are still unresolved issues in cobalamin biosynthesis that need to be elucidated for future bioprocess improvements. In the present work, we review the current state of development and challenges for cobalamin (vitamin B12) biosynthesis, describing the major and novel prospective strains, and the studies of environmental factors and genetic tools effecting on the fermentation process are reported.

Biosynthesis of Tetrapyrrole Cofactors by Bacterial Community Inhabiting Porphyrine-Containing Shale Rock (Fore-Sudetic Monocline)

“…According to Lu et al [41], only about 10% of 155 soil microbial metagenomes contained complete cobalamin biosynthetic pathway. Similar results were obtained by Balabanova et al [42], who found that the primary producers of cobalamin in the soil microbiome were bacteria of the genera Proteobacteria, Actinobacteria, Firmicutes, and Nitrospirae, which made up a small percentage of the community. The remaining microorganisms were only able to transport cobalamin.…”

“…One explanation for this phenomenon is that there are still undiscovered pathways in the biosynthesis of tetrapyrrole cofactors in bacteria [43]. However, incomplete pathways, including pathways in which microorganisms uptake readymade tetrapyrrole cofactors such as heme [44][45][46] and cobalamin [2,41,42] from the environment, have also been established. These studies have emphasized that the microorganisms transport cofactors from external sources.…”

Cobalamin cbiP mutant shows decreased tolerance to low temperature and copper stress in Listeria monocytogenes

“…It has been proposed that the evolution of the cyanocobalamin synthesis pathway allowed the fermentation of small molecules such as ethanolamine, 1,2-propanediol, and glycerol in anaerobic environments [ 20 ]. De novo cobalamin synthesis occurs in bacteria and archaea, and some species also may synthesize cobalamin by absorbing corrinoids through the salvage pathway [ 40 ].…”

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

“…Later, the phosphoribosyltransferase CobU/T (EC 2.4.2.21) introduces the DMBI via a nucleophilic substitution reaction [ 34 ]. This pathway was firstly described for S. meliloti [ 35 ] and later found in the majority of Cbl-producing bacteria [ 36 ], including the two most important industrial producers, P. freudenreichii [ 37 ] and P. denitrificans [ 38 ]. This fact highlighted the incapacity of P. freudenreichii to completely produce Cbl anaerobically without any external addition of DMBI.…”