Cobalamin riboswitch is a cis-regulatory element which is widely distributed in 5' untranslated regions of vitamin B12 (Cobalamin) related genes in bacteria. Cobalamin (vitamin B12, coenzyme B12 ) riboswitches are structured RNA elements that regulate adjacent genes related to cobalamin metabolism in response to cobalamin binding. Riboswitches are RNA-based genetic regulatory elements present in the 5’ untranslated region (5'UTR) of primarily bacterial RNA. These switches bind to a ligand, which is generally a metabolite, with high affinity and specificity. Ligand binding mediates allosteric rearrangement of mRNA structure, and this results in modulation of gene expression or translation of mRNA to yield a protein. The cobalamin riboswitch, along with most other riboswitches, are cis-regulatory. This means they regulate genes involved in the same metabolic pathways as the metabolite they bind, which creates regulation through a negative feedback loop. Riboswitches are grouped into classes by the ligand that they bind because the ligand-binding or aptamer domain is highly conserved across species. Riboswitches, including the cobalamin riboswitch, have garnered a lot of attention recently due to their therapeutic and synthetic potential, as well as their interesting structural properties. As of 2019, cobalamin riboswitches have been identified in over 5000 species of bacteria. Ligand selectivity Cobalamin riboswitches bind cobalamin (vitamin B12), which is a complex enzyme cofactor composed of a corrin ring coordinated to a cobalt (III) ion. In the alpha-axial position, the cobalt is coordinated to a dimethylbenzimidazole moiety attached to the corrin ring via a flexible aminopropanol linker. The active portion of the cofactor is in the beta-axial position. Methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) are the biologically active forms of cobalamin, containing a methyl group and an adenosyl moiety in the beta-axial position, respectively. Hydroxocobalamin (HyCbl), with a hydroxyl group in the beta-axial position, is produced as a result of cobalamin photolysis, and is present in biological conditions but is not in an active form. Cyanocobalamin (CyCbl) is an artificial form of cobalamin found in supplements, which can be converted to active forms of cobalamin. Cobalamin riboswitches can exhibit selectivity toward different forms of cobalamin. Structure and classes riboswitches, including the cobalamin riboswitch, are generally composed of a ligand-binding or aptamer domain and an expression platform. Ligand binding induces an allosteric structural rearrangement in the expression platform that results in the regulation of gene expression via transcriptional or translational mechanisms. Class I (Cbl-I) Cobalamin riboswitches are broadly classified by the identity of