A revised biosynthetic pathway for the cofactor F 420 in prokaryotes

Cofactor F 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 methanogenesi...

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Veröffentlicht in:Nature communications 2019-12, Vol.10 (1), p.1558
Hauptverfasser: Bashiri, Ghader, Antoney, James, Jirgis, Ehab N M, Shah, Mihir V, Ney, Blair, Copp, Janine, Stuteley, Stephanie M, Sreebhavan, Sreevalsan, Palmer, Brian, Middleditch, Martin, Tokuriki, Nobuhiko, Greening, Chris, Scott, Colin, Baker, Edward N, Jackson, Colin J
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Sprache:eng
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Zusammenfassung:Cofactor F 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 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 -0. The C-terminal domain of FbiB then utilizes FMNH to reduce dehydro-F -0, which produces mature F species when combined with the γ-glutamyl ligase activity of the N-terminal domain. These new insights have allowed the heterologous production of F from a recombinant F biosynthetic pathway in Escherichia coli.
ISSN:2041-1723
DOI:10.1038/s41467-019-09534-x