FIGURE 1: Biosynthesis of 5,6-dimethylbenzimidazole (DMB) and its incorporation into coenzyme B₁₂ (CoB₁₂). (A) Aerobic pathway of DMB biosynthesis involves oxidative fragmentation of reduced flavin mononucleotide (FMNH₂) by DMB synthase, BluB. Atoms of the isoalloxazine ring and ribityl tail of FMNH₂ converted into DMB are shown in red. (B) In S. Typhimurium incorporation of DMB into CoB₁₂ is initiated by its activation into the alpha ribotide, α-ribazole-5′-phosphate (α-RP) followed by condensation of activated intermediates and dephosphorylation to yield biologically active CoB₁₂. Abbreviations: FMN, flavin mononucleotide; NAD(P), nicotinamide adenine dinucleotide (phosphate); NaMN, nicotinate mononucleotide; Na, nicotinate; AdoCbi-GDP, adenosylcobinamide- guanosine diphosphate. GMP, guanosine monophosphate; AdoCbl-P, adenosylcobalamin-phosphate; AdoCbl, adenosylcobalamin; CobT, NaMN:DMB phosphoribosyltransferase; CobS, AdoCbl-5' phosphate synthase; CobC, adenosylcobalamin phosphatase; Fre, NAD(P)H:flavin reductase. Enzyme homologs presence in S. Typhimurium are shown in red circles. The rhomboid structure with the Co³⁺ ion in the middle is a cartoon of the complex cyclic tetrapyrrole ring shown at the end of the pathway.