A revised biosynthetic pathway for the cofactor F420 in prokaryotes

Ghader Bashiri, James Antoney, Ehab N.M. Jirgis, Mihir V. Shah, Blair Ney, Janine Copp, Stephanie M. Stuteley, Sreevalsan Sreebhavan, Brian Palmer, Martin Middleditch, Nobuhiko Tokuriki, Chris Greening, Colin Scott, Edward N. Baker, Colin J. Jackson

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5 Citations (Scopus)

Abstract

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 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.

Original languageEnglish
Article number1558
Number of pages12
JournalNature Communications
Volume10
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

Cite this

Bashiri, G., Antoney, J., Jirgis, E. N. M., Shah, M. V., Ney, B., Copp, J., ... Jackson, C. J. (2019). A revised biosynthetic pathway for the cofactor F420 in prokaryotes. Nature Communications, 10(1), [1558]. https://doi.org/10.1038/s41467-019-09534-x
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. / A revised biosynthetic pathway for the cofactor F420 in prokaryotes. In: Nature Communications. 2019 ; Vol. 10, No. 1.
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abstract = "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 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.",
author = "Ghader Bashiri and James Antoney and Jirgis, {Ehab N.M.} and Shah, {Mihir V.} and Blair Ney and Janine Copp and Stuteley, {Stephanie M.} and Sreevalsan Sreebhavan and Brian Palmer and Martin Middleditch and Nobuhiko Tokuriki and Chris Greening and Colin Scott and Baker, {Edward N.} and Jackson, {Colin J.}",
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Bashiri, G, Antoney, J, Jirgis, ENM, Shah, MV, Ney, B, Copp, J, Stuteley, SM, Sreebhavan, S, Palmer, B, Middleditch, M, Tokuriki, N, Greening, C, Scott, C, Baker, EN & Jackson, CJ 2019, 'A revised biosynthetic pathway for the cofactor F420 in prokaryotes', Nature Communications, vol. 10, no. 1, 1558. https://doi.org/10.1038/s41467-019-09534-x

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

In: Nature Communications, Vol. 10, No. 1, 1558, 01.12.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A revised biosynthetic pathway for the cofactor F420 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.

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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 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 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 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.

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U2 - 10.1038/s41467-019-09534-x

DO - 10.1038/s41467-019-09534-x

M3 - Article

VL - 10

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 1558

ER -

Bashiri G, Antoney J, Jirgis ENM, Shah MV, Ney B, Copp J et al. A revised biosynthetic pathway for the cofactor F420 in prokaryotes. Nature Communications. 2019 Dec 1;10(1). 1558. https://doi.org/10.1038/s41467-019-09534-x