title: Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B₁₂ Biosynthesis.
abstract: Comparative genomics of the bacterial thiamin pyrimidine synthase (thiC) revealed a paralogue of thiC (bzaF) clustered with anaerobic vitamin B12 biosynthetic genes. Here we demonstrate that BzaF is a radical S-adenosylmethionine enzyme that catalyzes the remarkable conversion of aminoimidazole ribotide (AIR) to 5-hydroxybenzimidazole (5-HBI). We identify the origin of key product atoms and propose a reaction mechanism. These studies represent the first step in solving a long-standing problem in anaerobic vitamin B12 assembly and reveal an unanticipated intersection of thiamin and vitamin B12 biosynthesis.
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Angad P
authors.initials: AP
authors.lastname: Mehta
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.|Therapeutic Chemistry Department, National Research Centre , Dokki, Cairo, Egypt.
authors.forename: Sameh H
authors.initials: SH
authors.lastname: Abdelwahed
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , 120 Baker Lab, Ithaca, New York 14853, United States.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Fenwick
authors.affiliation: Department of Plant and Microbial Biology, University of California , Berkeley, California 94720, United States.
authors.forename: Amrita B
authors.initials: AB
authors.lastname: Hazra
authors.affiliation: Department of Plant and Microbial Biology, University of California , Berkeley, California 94720, United States.
authors.forename: Michiko E
authors.initials: ME
authors.lastname: Taga
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , 120 Baker Lab, Ithaca, New York 14853, United States.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University , 120 Baker Lab, Ithaca, New York 14853, United States.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Ealick
authors.affiliation: Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
authors.forename: Tadhg P
authors.initials: TP
authors.lastname: Begley
mesh_terms: D000693:Anaerobiosis; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D001562:Benzimidazoles / Q000378:metabolism*; D055162:Biocatalysis; D008958:Models, Molecular; D011487:Protein Conformation; D012265:Ribonucleotides / Q000378:metabolism*; D013831:Thiamine / Q000096:biosynthesis*; D014805:Vitamin B 12 / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D001562:Benzimidazoles; D012265:Ribonucleotides; C024828:aminoimidazole ribotide; C036435:5-hydroxybenzimidazole; D014805:Vitamin B 12; D013831:Thiamine