TY - JOUR
T1 - A revised biosynthetic pathway for the cofactor F 420 in prokaryotes
AU - Bashiri, Ghader
AU - Antoney, James
AU - Jirgis, Ehab N.M.
AU - Shah, Mihir V.
AU - Ney, Blair
AU - Copp, Janine
AU - Stuteley, Stephanie M.
AU - Sreebhavan, Sreevalsan
AU - Palmer, Brian
AU - Middleditch, Martin
AU - Tokuriki, Nobuhiko
AU - Greening, Chris
AU - Scott, Colin
AU - Baker, Edward N.
AU - Jackson, Colin J.
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Cofactor F 420 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 F 420 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-F 420 -0. The C-terminal domain of FbiB then utilizes FMNH 2 to reduce dehydro-F 420 -0, which produces mature F 420 species when combined with the γ-glutamyl ligase activity of the N-terminal domain. These new insights have allowed the heterologous production of F 420 from a recombinant F 420 biosynthetic pathway in Escherichia coli.
AB - Cofactor F 420 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 F 420 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-F 420 -0. The C-terminal domain of FbiB then utilizes FMNH 2 to reduce dehydro-F 420 -0, which produces mature F 420 species when combined with the γ-glutamyl ligase activity of the N-terminal domain. These new insights have allowed the heterologous production of F 420 from a recombinant F 420 biosynthetic pathway in Escherichia coli.
UR - http://www.scopus.com/inward/record.url?scp=85063990479&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-09534-x
DO - 10.1038/s41467-019-09534-x
M3 - Article
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1558
ER -