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. 2026 Mar 30;208(4):e00345-25. doi: 10.1128/jb.00345-25

Fig 4.

Pathway diagram showing molecular structures linked by arrows and enzyme names. Transformation sequence displays increasing complexity from ribulose phosphate to riboflavin and flavin cofactors.

Potential riboflavin synthesis pathways in H. volcanii (48–50). Riboflavin biosynthesis utilizes ribulose-5-phosphate (R5P) as a precursor. R5P is converted to 3,4-dihydroxy-2-butanone-4-phosphate (DHBP) by DHBPP synthase (ribB). Subsequently, lumazine synthase (ribH) catalyzes the condensation of DHBP to form 6,7-dimethyl-8-ribityllumazine (DRL). Riboflavin synthase (ribE) then converts DRL into riboflavin. For metabolic utilization, riboflavin undergoes phosphorylation. Archaeal riboflavin kinase (RFK) utilizes ATP to convert riboflavin into flavin mononucleotide (FMN). Flavin adenine dinucleotide (FAD) synthase (FLAD1) then adenylates FMN to generate FAD. Finally, FMN reductase (ssuE) reduces both FMN and FAD to their hydroquinone forms, FMNH2 and FADH2, respectively.