Biosynthesis of F-0, Precursor of the F-420 Cofactor, Requires a Unique Two Radical-SAM Domain Enzyme and Tyrosine as Substrate

Laure L. Decamps (1) , Benjamin B. Philmus (2) , Alhosna A. Benjdia (3) , Robert R. White (4) , Tadhg P. T. P. Begley (2) , Olivier O. Berteau (1)

1 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
2 Dept Chem
3 Department of Biomolecular Mechanisms
4 Dept Biochem

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.

Mots clés: SULFATASE-MATURATING ENZYMES; COENZYME F-420; MYCOBACTERIUM-TUBERCULOSIS; ESCHERICHIA-COLI; IDENTIFICATION; 8-DIDEMETHYL-8-HYDROXY-5-DEAZARIBOFLAVIN; SUPERFAMILY; RIBOFLAVIN; MOAA; NO

Domaines: Sciences agricoles

Laure L. Decamps, Benjamin B. Philmus, Alhosna A. Benjdia, Robert R. White, Tadhg P. T. P. Begley, et al.. Biosynthesis of F-0, Precursor of the F-420 Cofactor, Requires a Unique Two Radical-SAM Domain Enzyme and Tyrosine as Substrate. Journal of the American Chemical Society, 2012, 134 (44), pp.18173 - 18176. ⟨10.1021/ja307762b⟩. ⟨hal-01004118⟩