Mehta Angad P, Abdelwahed Sameh H, Fenwick Michael K, Hazra Amrita B, Taga Michiko E, Zhang Yang, Ealick Steven E, Begley Tadhg P
Department of Chemistry, Texas A&M University , College Station, Texas 77843, United States.
Therapeutic Chemistry Department, National Research Centre , Dokki, Cairo, Egypt.
J Am Chem Soc. 2015 Aug 26;137(33):10444-7. doi: 10.1021/jacs.5b03576. Epub 2015 Aug 13.
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.
细菌硫胺嘧啶合酶(thiC)的比较基因组学研究表明,thiC的一个旁系同源物(bzaF)与厌氧维生素B12生物合成基因簇在一起。在此,我们证明BzaF是一种自由基S-腺苷甲硫氨酸酶,它催化氨基咪唑核糖核苷酸(AIR)向5-羟基苯并咪唑(5-HBI)的显著转化。我们确定了关键产物原子的来源并提出了反应机制。这些研究是解决厌氧维生素B12组装中长期存在问题的第一步,并揭示了硫胺素和维生素B12生物合成中一个意外的交叉点。