Publications

• A revised biosynthetic pathway for the cofactor F420 in prokaryotes.

  Bashiri G., Antoney J., Jirgis E.N.M., Shah M.V., Ney B., Copp J., Stuteley S.M., Sreebhavan S., Palmer B., Middleditch M., Tokuriki N., Greening C., Scott C., Baker E.N., Jackson C.J.

  Cofactor F₄₂₀ plays critical roles in primary and secondary metabolism in a range of bacteria and archaea as a low-potential hydride transfer agent. It mediates a variety of important redox transformations involved in bacterial persistence, antibiotic biosynthesis, pro-drug activation a ... >> More

  Cofactor F₄₂₀ plays critical roles in primary and secondary metabolism in a range of bacteria and archaea as a low-potential hydride transfer agent. It mediates a variety of important redox transformations involved in bacterial persistence, antibiotic biosynthesis, pro-drug activation and methanogenesis. However, the biosynthetic pathway for F₄₂₀ has not been fully elucidated: neither the enzyme that generates the putative intermediate 2-phospho-L-lactate, nor the function of the FMN-binding C-terminal domain of the γ-glutamyl ligase (FbiB) in bacteria are known. Here we present the structure of the guanylyltransferase FbiD and show that, along with its archaeal homolog CofC, it accepts phosphoenolpyruvate, rather than 2-phospho-L-lactate, as the substrate, leading to the formation of the previously uncharacterized intermediate dehydro-F₄₂₀-0. The C-terminal domain of FbiB then utilizes FMNH₂ to reduce dehydro-F₄₂₀-0, which produces mature F₄₂₀ species when combined with the γ-glutamyl ligase activity of the N-terminal domain. These new insights have allowed the heterologous production of F₄₂₀ from a recombinant F₄₂₀ biosynthetic pathway in Escherichia coli. << Less

  Nat. Commun. 10:1558-1558(2019) [PubMed] [EuropePMC]

  This publication is cited by 5 other entries.