The Conversion of a Phenol to an Aniline Occurs in the Biochemical Formation of the 1-(4-Aminophenyl)-1-deoxy-D-ribitol Moiety in Methanopterin

Recent work has demonstrated that 4-hydroxybenzoic acid is the in vivo precursor to the 1-(4-aminophenyl)-1-deoxy-D-ribitol (APDR) moiety present in the C-1 carrier coenzyme methanopterin present in the methanogenic archaea. For this transformation to occur, the hydroxyl group of the 4-hydroxybenzoic acid must be replaced with an amino group at some point in the biosynthetic pathway. Using stable isotopically labeled precursors and liquid chromatography with electrospray-ionization mass spectroscopy, the first step of this transformation in Methanocaldococcus jannaschii occurs by the reaction of 4-hydroxybenzoic acid with phosphoribosyl pyrophosphate (PRPP) to form 4-(beta-D-ribofuranosyl)hydroxybenzene 5'-phosphate (beta-RAH-P). The beta-RAH-P then condenses with L-aspartate in the presence of ATP to form 4-(beta-D-ribofuranosyl)-N-succinylaminobenzene 5'-phosphate (beta-RFSA-P). Elimination of fumarate from beta-RFSA-P produces 4-(beta-D-ribofuranosyl)aminobenzene S'-phosphate (beta-RFA-P), the known precursor to the APDR moiety of methanopterin [White, R. H. (1996) Biochemistry 35, 3447-3456]. This work represents the first biochemical example of the conversion of a phenol to an aniline.