that corresponds to a part of the cobalamin riboswitch, and a more complete conserved structure was identified. Variants of the riboswitch consensus have been identified. Before a broader range of cobalamin riboswitches were identified, it was believed that only AdoCbl riboswitches existed. Mechanism The mechanisms of individual cobalamin riboswitches can vary and many have not yet been elucidated. The four canonical mechanisms for riboswitches include transcriptional activation or repression and translational activation or repression. In transcriptional activation, a terminator loop, which blocks the RNA polymerase binding site, is present in the absence of ligand and upon ligand binding, an anti-terminator loop forms and the terminator hairpin is removed. Transcriptional termination occurs when the terminator stem loop forms in the presence of a ligand. Regulation via translational activation occurs when the Shine-Dalgarno (SD) sequence, necessary for the ribosome to bind to the mRNA and initiate translation, is sequestered within tertiary structural elements when the ligand is unbound and is made accessible after the riboswitch undergoes a ligand-induced conformational change. In translational repression, the SD is sequestered upon ligand binding. The E. coli btuB AdoCbl riboswitch and confirmed to regulate gene expression via a translational repression mechanism, as well as the env8 HyCbl riboswitch. Regulated Genes The cobalamin riboswitch is known to regulate a broad range of genes involved in cobalamin metabolism, including those genes coding for proteins involved in cobalamin biosynthesis and transport. Examples include regulation of the btuB gene in E. coli which codes for a cobalamin transport protein, regulation of CobA, an enzyme which converts uroporphyrinogen III to precorrin-2 during cobalamin biosynthesis in P. freudenreichiii, and the cobalamin biosynthesis (cob) operon in S. typhimurium among others. Applications As drug targets The emerging threat of antibiotic resistance highlights the need for novel antibiotic development. riboswitches, including cobalamin riboswitches, are currently being investigated as potential targets for novel antibiotics. Not only do they regulate essential metabolic processes, they are also primarily found in prokaryotes. Only one riboswitch (the TPP riboswitch) has been identified in some plant cells to date, and no riboswitches have been identified in mammalian cells. By targeting bacteria-specific regulatory mechanisms, the risk of host side-effects is minimized. Furthermore, the mechanism in which a ligand binds to its riboswitch is inherently different from how a protein binds that same ligand, thus minimizing interference between the two systems. A bioinformatic study performed in 2019, which analyzed eight different riboswitch classes