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.
Highlights
Vitamin B12 is an important nutrient for humans and animals, which plays a key coenzyme role in numerous mitochondrial and cytosolic pathways, methylation-mediated regulation, and regulation of sex steroids due to the host–microbe metabolic interactions, it is essential for gut microbiota themselves [1,2]
Among the hundred cyanobacteria genomes screened for the B12 biosynthetic genes, including those involved in the nucleotide loop assembly, pseudocobalamin is the form synthesized by cyanobacteria more broadly
The gut microbes have been suggested to be under reductive genomic evolution, driven by genetic drift, which is common in endosymbiotic bacteria and states that fitness gain accompanying gene loss is frequency dependent, demanding the B-vitamin donors must remain in sufficient abundance in communities to ensure that auxotrophs are not subject to negative selection [83]
Summary
Vitamin B12 is an important nutrient for humans and animals, which plays a key coenzyme role in numerous mitochondrial and cytosolic pathways (tricarboxylic acid cycle, one-carbon metabolism including methionine and folate cycles), methylation-mediated regulation (metabolites, DNA, RNA, and proteins), and regulation of sex steroids due to the host–microbe metabolic interactions, it is essential for gut microbiota themselves [1,2]. It is widely used as a dietary supplement, as medicine for treating hematologic and neurological disorders, and as important feed additives (growth enhancer) for fowls and domestic animals. We describe the microbial vitamin B12 synthesis and variations of metabolic pathways, as well as their abundance and auxotrophy in various ecosystems, providing characteristics of strategies that were applied to enhancement of cobalamin production on the lab and industrial scale
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