37333-48-5Relevant academic research and scientific papers
A robust synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin
Bender, Matthias,Mouritsen, Henrik,Christoffers, Jens
, p. 912 - 917 (2016)
The biosynthetic precursor of redox cofactor F420, 7,8-didemethyl-8-hydroxy-5-deazariboflavin, was prepared in four steps from 6-chlorouracil, 2-chloro-4-hydroxybenzaldehyde and bis-isopropylidene protected D-ribose. The latter aldehyde was transformed to the corresponding protected ribitylamine via the oxime, which was submitted to reduction with LiAlH4. Key advantage compared to previous syntheses is the utilization of a polyol-protective group which allowed the chromatographic purification of a key-intermediate product providing the target compound with high purity.
Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate
Decamps, Laure,Berteau, Olivier,Philmus, Benjamin,Begley, Tadhg P.,Benjdia, Alhosna,White, Robert
, p. 18173 - 18176,4 (2012)
Cofactors play key roles in metabolic pathways. Among them F420 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, F0-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 F0-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 F0-synthase generates two 5′- deoxyadenosyl radicals for catalysis which is unprecedented in reaction catalyzed by radical SAM enzymes.
Convenient synthesis of deazaflavin cofactor FO and its activity in F420-dependent NADP reductase
Hossain, Mohammad S.,Le, Cuong Q.,Joseph, Ebenezer,Nguyen, Toan Q.,Johnson-Winters, Kayunta,Foss, Frank W.
, p. 5082 - 5085 (2015/05/13)
F420 and FO are phenolic 5-deazaflavin cofactors that complement nicotinamide and flavin redox coenzymes in biochemical oxidoreductases and photocatalytic systems. Specifically, these 5-deazaflavins lack the single electron reactivity with O2 of riboflavin-derived coenzymes (FMN and FAD), and, in general, have a more negative redox potential than NAD(P)+. For example, F420-dependent NADP+ oxidoreductase (Fno) is critical to the conversion of CO2 to CH4 by methanogenic archaea, while FO functions as a light-harvesting agent in DNA repair. The preparation of these cofactors is an obstacle to their use in biochemical studies and biotechnology. Here, a convenient synthesis of FO was achieved by improving the redox stability of synthetic intermediates containing a polar, electron-rich aminophenol fragment. Improved yields and simplified purification techniques for FO are described. Additionally, Fno activity was restored with FO in the absence of F420. Investigating the FO-dependent NADP+/NADPH redox process by stopped-flow spectrophotometry, steady state kinetics were defined as having a Km of 4.00 ± 0.39 μM and a kcat of 5.27 ± 0.14 s-1. The preparation of FO should enable future biochemical studies and novel uses of F420 mimics.
Biosynthetic versatility and coordinated action of 5′-deoxyadenosyl radicals in deazaflavin biosynthesis
Philmus, Benjamin,Decamps, Laure,Berteau, Olivier,Begley, Tadhg P.
supporting information, p. 5406 - 5413 (2015/05/13)
Coenzyme F420 is a redox cofactor found in methanogens and in various actinobacteria. Despite the major biological importance of this cofactor, the biosynthesis of its deazaflavin core (8-hydroxy-5-deazaflavin, Fo) is still poorly understood. Fo synthase, the enzyme involved, is an unusual multidomain radical SAM enzyme that uses two separate 5′-deoxyadenosyl radicals to catalyze Fo formation. In this paper, we report a detailed mechanistic study on this complex enzyme that led us to identify (1) the hydrogen atoms abstracted from the substrate by the two radical SAM domains, (2) the second tyrosine-derived product, (3) the reaction product of the CofH-catalyzed reaction, (4) the demonstration that this product is a substrate for CofG, and (5) a stereochemical study that is consistent with the formation of a p-hydroxybenzyl radical at the CofH active site. These results enable us to propose a mechanism for Fo synthase and uncover a new catalytic motif in radical SAM enzymology involving the use of two 5′-deoxyadenosyl radicals to mediate the formation of a complex heterocycle.
Biosynthesis of F0, precursor of the F420 cofactor, requires a unique two radical-SAM domain enzyme and tyrosine as substrate
Decamps, Laure,Philmus, Benjamin,Benjdia, Alhosna,White, Robert,Begley, Tadhg P.,Berteau, Olivier
supporting information, p. 18173 - 18176 (2013/01/15)
Cofactors play key roles in metabolic pathways. Among them F420 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, F0-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 F0-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 F0-synthase generates two 5′- deoxyadenosyl radicals for catalysis which is unprecedented in reaction catalyzed by radical SAM enzymes.
First Total Synthesis of Redox Coenzyme Factor 420
Tanaka, Kiyoshi,Kimachi, Tetsutaro,Kawase, Masahiro,Yoneda, Fumio
, p. 524 - 526 (2007/10/02)
The first total synthesis of Methanobacterium redox coenzyme Factor 420 (F20) has been achieved by the formation of a phosphotriester bond between a protected 10-D-ribityl-8-hydroxy-5-deazaisoalloxazine moiety and a peptide moiety, (L-lactate-γ-L-glutamyl)-L-glutamic acid tribenzyl ester, by the phosphite triester approach using β,β,β-trichloroethyl phosphorodichloridite, followed by successive deprotection.
