Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate

J Am Chem Soc. 2012 Nov 7;134(44):18173-6. doi: 10.1021/ja307762b. Epub 2012 Oct 24.


Cofactors play key roles in metabolic pathways. Among them F(420) has proved to be a very attractive target for the selective inhibition of archaea and actinobacteria. Its biosynthesis, in a unique manner, involves a key enzyme, F(0)-synthase. This enzyme is a large monomer in actinobacteria, while it is constituted of two subunits in archaea and cyanobacteria. We report here the purification of both types of F(0)-synthase and their in vitro activities. Our study allows us to establish that F(0)-synthase, from both types, uses 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione and tyrosine as substrates but not 4-hydroxylphenylpyruvate as previously suggested. Furthermore, our data support the fact that F(0)-synthase generates two 5'-deoxyadenosyl radicals for catalysis which is unprecedented in reaction catalyzed by radical SAM enzymes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actinomycetales / chemistry
  • Actinomycetales / enzymology*
  • Actinomycetales / metabolism
  • Methanococcus / chemistry
  • Methanococcus / enzymology*
  • Methanococcus / metabolism
  • Nostoc / chemistry
  • Nostoc / enzymology*
  • Nostoc / metabolism
  • Protein Structure, Tertiary
  • Riboflavin / analogs & derivatives*
  • Riboflavin / chemistry
  • Riboflavin / metabolism
  • Riboflavin Synthase / chemistry
  • Riboflavin Synthase / metabolism*
  • S-Adenosylmethionine / chemistry
  • S-Adenosylmethionine / metabolism
  • Tyrosine / metabolism*


  • Tyrosine
  • coenzyme F420
  • S-Adenosylmethionine
  • Riboflavin Synthase
  • Riboflavin