Anaerobic 5-Hydroxybenzimidazole Formation from Aminoimidazole Ribotide: An Unanticipated Intersection of Thiamin and Vitamin B₁₂ Biosynthesis

J Am Chem Soc. 2015 Aug 26;137(33):10444-7. doi: 10.1021/jacs.5b03576. Epub 2015 Aug 13.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaerobiosis
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Benzimidazoles / metabolism*
  • Biocatalysis
  • Models, Molecular
  • Protein Conformation
  • Ribonucleotides / metabolism*
  • Thiamine / biosynthesis*
  • Vitamin B 12 / biosynthesis*

Substances

  • Bacterial Proteins
  • Benzimidazoles
  • Ribonucleotides
  • aminoimidazole ribotide
  • 5-hydroxybenzimidazole
  • Vitamin B 12
  • Thiamine